Science.gov

Sample records for acute locomotor stimulant

  1. Effect of caffeine on cocaine locomotor stimulant activity in rats.

    PubMed

    Misra, A L; Vadlamani, N L; Pontani, R B

    1986-03-01

    The effect of caffeine on the locomotor stimulant activity induced by intravenous cocaine in rats was investigated. Low doses of caffeine (20 mg/kg IP) potentiated the locomotor activity induced by 1, 2.5 mg/kg intravenous doses of cocaine and higher doses of caffeine (50, 100 mg/kg IP) had no significant effect. The locomotor stimulant effect of 20 mg/kg IP dose of caffeine per se in vehicle was significantly higher and that with 100 mg/kg dose significantly lower than that of the vehicle control. Thus caffeine produced dose-dependent effects on cocaine-induced locomotor stimulant activity, with low dose potentiating and higher doses having no significant effect on such activity. Pharmacokinetic or dispositional factors did not appear to play a role in potentiation of cocaine locomotor stimulant activity by caffeine. PMID:3703910

  2. Acute Neuroactive Drug Exposures alter Locomotor Activity in Larval Zebrafish

    EPA Science Inventory

    As part of the development of a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae by assessing the acute effects of prototypic drugs that act on the central nervous system. Initially,...

  3. Evidence for a role of endogenous neurotensin in the development of sensitization to the locomotor stimulant effect of morphine.

    PubMed

    Lévesque, Karine; Lamarche, Caroline; Rompré, Pierre-Paul

    2008-10-10

    This experiment was aimed at exploring the role of endogenous neurotensin in the development of sensitization to the locomotor stimulant effect of morphine. During the induction phase (Days 1, 3, 5 and 7), male Long-Evans adult rats were treated with the neurotensin antagonist SR-48692 (160, 320 or 640 microg/kg, i.p.) or its vehicle, followed by morphine (5.0 mg/kg, i.p.) or its vehicle, and their locomotor activity (ambulatory, non-ambulatory and vertical activity) was measured for 2 h. One week after the last injection, each group received a single injection of morphine (2.5 mg/kg, i.p.) and their locomotor activity was again measured for 2 h (sensitization test, day 14). Results show that SR-48692 alone did not change locomotion. Morphine stimulated locomotor activity, an effect that was stronger on day 7 than on day 1. The two higher doses of SR-48692 attenuated the acute stimulant effect of morphine and prevented the observed increase from day 1 to day 7. The sensitization test on day 14 showed that rats pre-treated with morphine alone displayed significantly stronger ambulatory and vertical activity than vehicle pre-treated rats, a sensitization effect that was attenuated by SR-48692. The present results suggest that endogenous neurotensin contributes to the acute locomotor stimulant effect of morphine and to the induction of its sensitization. PMID:18706409

  4. Locomotor stimulant and discriminative stimulus effects of 'bath salt' cathinones.

    PubMed

    Gatch, Michael B; Taylor, Cynthia M; Forster, Michael J

    2013-09-01

    A number of psychostimulant-like cathinone compounds are being sold as 'legal' alternatives to methamphetamine or cocaine. The purpose of these experiments was to determine whether cathinone compounds stimulate motor activity and have discriminative stimulus effects similar to those of cocaine and/or methamphetamine. 3,4-Methylenedioxypyrovalerone (MDPV), methylone, mephedrone, naphyrone, flephedrone, and butylone were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally) or methamphetamine (1 mg/kg, intraperitoneally) from saline. All compounds fully substituted for the discriminative stimulus effects of cocaine and methamphetamine. Several commonly marketed cathinones produce discriminative stimulus effects comparable with those of cocaine and methamphetamine, which suggests that these compounds are likely to have similar abuse liabilities. MDPV and naphyrone produced locomotor stimulant effects that lasted much longer than those of cocaine or methamphetamine and therefore may be of particular concern, particularly because MDPV is one of the most commonly found substances associated with emergency room visits because of adverse effects of taking 'bath salts'. PMID:23839026

  5. Effects of cocaine on norepinephrine stimulated phosphoinositide hydrolysis and locomotor activity in rat

    SciTech Connect

    Mosaddeghi, M.

    1989-01-01

    The function of {alpha}{sub 1}-adrenoceptors was determined by stimulating cortical tissue slices, which were pre-labeled with ({sup 3}H)inositol, with norepinephrine (NE) in the presence of 8 mM LiCl. Results of in vitro studies showed that cocaine 10 {mu}M potentiated maximal NE-stimulated PI hydrolysis by 30%. In addition, the EC{sub 50} was decreased from 3.93 {plus minus} 0.42 to 1.91 {plus minus} 0.31 {mu}M NE. Concentrations of 0.1-100 {mu}M and 0.1-10 {mu}M cocaine enhanced PI hydrolysis stimulated by 0.3 and 3 {mu}M NE, respectively. The concentration-effect curves for NE-stimulated PI hydrolysis were shifted to the right 100-fold in the presence of 0.1 {mu}M prazosin. Cocaine (10 {mu}M) did not potentiate NE-stimulated PI hydrolysis in the presence of 0.1 {mu}M prazosin. ({sup 3}H)Prazosin saturation and NE ({sup 3}H)prazosin competition binding studies using crude membrane preparations showed that 10 {mu}M cocaine did not alter binding parameters B{sub max}, K{sub d}, Hill slope, and IC{sub 50}. Together, these results implied that cocaine in vitro potentiated NE-stimulated PI hydrolysis by blocking NE reuptake. For in vivo studies, the locomotor activity was determined after an acute or chronic injections of either cocaine or saline. Cocaine or saline-treated rats were killed after measurement of the locomotor activity, and NE-stimulated PI hydrolysis was measured. Acute administration of cocaine 3.2-42 mg/kg (i.p.) produced an inverted U shaped dose-response curve on locomotor activity. The peak increase in locomotor activity was at 32 mg/kg cocaine. A dose of 42 mg/kg cocaine produced a significant depression of maximal NE-stimulated PI hydrolysis.

  6. Initiation of segmental locomotor-like activities by stimulation of ventrolateral funiculus in the neonatal rat.

    PubMed

    Cheng, Jianguo; Magnuson, David S K

    2011-09-01

    Descending control is critically important for the generation of locomotor activities. Yet, our understanding of the descending control system of locomotion is limited. We hypothesized that stimulation of the ventrolateral funiculus (VLF) induces rhythmic activity in lumbar neurons that is correlated with locomotor-like activity in the neonatal rat. Intracellular recordings were conducted in the L2-L3 lumbar segments, while locomotor-like output was monitored in the L2 and L5 ventral roots. Stimulation of the VLF at thoracic segments induced locomotor-like activity in the L2 and L5 ventral roots in majority of the preparations (26/33). In a few midline split cord preparations (4/13), VLF stimulation induced rhythmic locomotor-like bursts in either L2 or L5 ventral root without alternating pattern between the ventral roots. The response latencies suggest that VLF stimulation induced antidromic activation (<1 ms, 8 cells), monosynaptic activation (1-3 ms, 18 cells), and oligosynaptic activation (3.5-5 ms, 14 cells) of segmental neurons in the lumbar region. VLF stimulation induced rhythmic membrane potential oscillations with or without bursting of action potentials in 9 of 40 putative interneurons. The membrane potential oscillations were in phase with the locomotor-like output of the L2 ventral root in 7 of the 9 cells while the other 2 cells oscillated in phase with the L5 ventral root activity. We have thus demonstrated that descending axons exist in the VLF which make synaptic connections with segmental neurons in the lumbar region that may be a critical element of the locomotor neural network for the initiation of locomotion. PMID:21858680

  7. Initiation of segmental locomotor-like activities by stimulation of ventrolateral funiculus in the neonatal rat

    PubMed Central

    Magnuson, David S. K.

    2011-01-01

    Descending control is critically important for the generation of locomotor activities. Yet, our understanding of the descending control system of locomotion is limited. We hypothesized that stimulation of the ventrolateral funiculus (VLF) induces rhythmic activity in lumbar neurons that is correlated with locomotor-like activity in the neonatal rat. Intracellular recordings were conducted in the L2–L3 lumbar segments, while locomotor-like output was monitored in the L2 and L5 ventral roots. Stimulation of the VLF at thoracic segments induced locomotor-like activity in the L2 and L5 ventral roots in majority of the preparations (26/33). In a few midline split cord preparations (4/13), VLF stimulation induced rhythmic locomotor-like bursts in either L2 or L5 ventral root without alternating pattern between the ventral roots. The response latencies suggest that VLF stimulation induced antidromic activation (<1 ms, 8 cells), monosynaptic activation (1–3 ms, 18 cells), and oligosynaptic activation (3.5–5 ms, 14 cells) of segmental neurons in the lumbar region. VLF stimulation induced rhythmic membrane potential oscillations with or without bursting of action potentials in 9 of 40 putative interneurons. The membrane potential oscillations were in phase with the locomotor-like output of the L2 ventral root in 7 of the 9 cells while the other 2 cells oscillated in phase with the L5 ventral root activity. We have thus demonstrated that descending axons exist in the VLF which make synaptic connections with segmental neurons in the lumbar region that may be a critical element of the locomotor neural network for the initiation of locomotion. PMID:21858680

  8. Assessing locomotor-stimulating effects of cocaine in rodents.

    PubMed

    Morgan, Drake; Dupree, Jameson P; Bibbey, Alex D; Sizemore, Glen M

    2012-01-01

    Locomotor activity procedures are useful for characterizing the behavioral effects of a drug, the influence of pharmacological, neurobiological, and environmental manipulations on drug sensitivity, and changes in activity following repeated administration (e.g., tolerance or sensitization) are thought to be related to the development of an addiction-like behavioral phenotype. The effects of cocaine on locomotor activity have been relatively extensively characterized. Many of the published studies use between-subject experimental designs, even though changes in sensitivity within a particular individual due to experimental manipulations, or behavioral and pharmacological histories is potentially the most important outcome as these changes may relate to differential development of an addiction-like phenotype in some, but not all, animals (including humans). The two behavioral protocols described herein allow extensive within-subject analyses. The first protocol uses daily locomotor activity levels as a stable baseline to assess the effects of experimental manipulations, and the second uses a pre- versus post-session experimental design to demonstrate the importance of drug-environment interactions in determining the behavioral effects of cocaine. PMID:22231824

  9. Efficacy of Stochastic Vestibular Stimulation to Improve Locomotor Performance in a Discordant Sensory Environment

    NASA Technical Reports Server (NTRS)

    Temple, D. R.; De Dios, Y. E.; Layne, C. S.; Bloomberg, J. J.; Mulavara, A. P.

    2016-01-01

    Astronauts exposed to microgravity face sensorimotor challenges incurred when readapting to a gravitational environment. Sensorimotor Adaptability (SA) training has been proposed as a countermeasure to improve locomotor performance during re-adaptation, and it is suggested that the benefits of SA training may be further enhanced by improving detection of weak sensory signals via mechanisms such as stochastic resonance when a non-zero level of stochastic white noise based electrical stimulation is applied to the vestibular system (stochastic vestibular stimulation, SVS). The purpose of this study was to test the efficacy of using SVS to improve short-term adaptation in a sensory discordant environment during performance of a locomotor task.

  10. Acute neuroactive drug exposures alter locomotor activity in larval zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA's prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after exposure to prototypic drugs that act on the central nervous system. MPTP (1-methyl-4phenyl- 1 ,2,3,6-...

  11. The alcohol-induced locomotor stimulation and accumbal dopamine release is suppressed in ghrelin knockout mice.

    PubMed

    Jerlhag, Elisabet; Landgren, Sara; Egecioglu, Emil; Dickson, Suzanne L; Engel, Jörgen A

    2011-06-01

    Ghrelin, the first endogenous ligand for the type 1A growth hormone secretagogue receptor (GHS-R1A), plays a role in energy balance, feeding behavior, and reward. Previously, we showed that pharmacologic and genetic suppression of the GHS-R1A attenuates the alcohol-induced stimulation, accumbal dopamine release, and conditioned place preference as well as alcohol consumption in mice, implying that the GHS-R1A is required for alcohol reward. The present study further elucidates the role of ghrelin for alcohol-induced dopamine release in nucleus accumbens and locomotor stimulation by means of ghrelin knockout mice. We found that the ability of alcohol to increase accumbal dopamine release in wild-type mice is not observed in ghrelin knockout mice. Furthermore, alcohol induced a locomotor stimulation in the wild-type mice and ghrelin knockout mice; however, the locomotor stimulation in homozygote mice was significantly lower than in the wild-type mice. The present series of experiments suggest that endogenous ghrelin may be required for the ability of alcohol to activate the mesolimbic dopamine system. PMID:21145690

  12. Restraint stress attenuates nicotine’s locomotor stimulant but not discriminative stimulus effects in rats

    PubMed Central

    Harris, Andrew C.; Mattson, Christina; Shelley, David; LeSage, Mark G.

    2014-01-01

    Stress enhances the locomotor stimulant and discriminative stimulus effects of several addictive drugs (e.g., morphine) in rodents, yet interactions between stress and nicotine’s effects in these behavioral models have not been well established. To this end, the current studies examined the effects of restraint stress on nicotine-induced locomotor activity and nicotine discrimination in rats. We used a novel approach in which onset of stress and nicotine administration occurred concurrently (i.e., simultaneous exposure) to simulate effects of stress on ongoing tobacco use, as well as a more traditional approach in which a delay was imposed between stress and nicotine administration (i.e., sequential exposure). Simultaneous exposure to stress reduced the rate of locomotor sensitization induced by daily injections of nicotine (0.4 mg/kg, s.c.). A lower dose of nicotine (0.1 mg/kg, s.c.) produced modest effects on activity that were generally unaffected by simultaneous exposure to stress. Sequential exposure to stress and nicotine (0.4 mg/kg, s.c.) slightly suppressed nicotine-induced activity, but did not influence rate of locomotor sensitization. Neither simultaneous nor sequential exposure to stress influenced the discriminative stimulus effects of nicotine (0.01 – 0.2 mg/kg, s.c.). These data show that restraint stress reduces nicotine’s locomotor stimulant effects, particularly when onset of stress and nicotine exposure occurs simultaneously, but does not influence nicotine discrimination. These findings contrast with the ability of stress to enhance the effects of other drugs in these models. This study also suggests that studying the influence of simultaneous stress exposure on drug effects may be useful for understanding the role of stress in addiction. PMID:24867077

  13. Ceftriaxone attenuates locomotor activity induced by acute and repeated cocaine exposure in mice.

    PubMed

    Tallarida, Christopher S; Corley, Gladys; Kovalevich, Jane; Yen, William; Langford, Dianne; Rawls, Scott M

    2013-11-27

    Ceftriaxone (CTX) decreases locomotor activation produced by initial cocaine exposure and attenuates development of behavioral sensitization produced by repeated cocaine exposure. An important question that has not yet been answered is whether or not CTX reduces behavioral sensitization to cocaine in cases in which the antibiotic is administered only during the period of cocaine absence that follows repeated cocaine exposure and precedes reintroduction to cocaine. We investigated this question using C57BL/6 mice. Mice pretreated with cocaine (15mg/kg×14 days) and then challenged with cocaine (15mg/kg) after 30 days of cocaine absence displayed sensitization of locomotor activity. For combination experiments, CTX injected during the 30 days of cocaine absence attenuated behavioral sensitization produced by cocaine challenge. In the case in which CTX was injected together with cocaine for 14 days, development of behavioral sensitization to cocaine challenge was also reduced. CTX attenuated the increase in locomotor activity produced by acute cocaine exposure; however, its efficacy was dependent on the dose of cocaine as inhibition was detected against 30mg/kg, but not 15mg/kg, of cocaine. These results from mice indicate that CTX attenuates locomotor activity produced by acute and repeated cocaine exposure and counters cocaine's locomotor activating properties in a paradigm in which the antibiotic is injected during the period of forced cocaine absence that follows repeated cocaine exposure. PMID:24120434

  14. Locomotor Stimulant and Discriminative Stimulus Effects of “Bath Salt” Cathinones

    PubMed Central

    Gatch, Michael B.; Taylor, Cynthia M.; Forster, Michael J.

    2014-01-01

    A number of psychostimulant-like cathinone compounds are being sold as “legal” alternatives to methamphetamine or cocaine. The purpose of these experiments was to determine whether cathinone compounds stimulate motor activity and have discriminative stimulus effects similar to cocaine and/or methamphetamine. 3,4-Methylenedioxypyrovalerone (MDPV), methylone, mephedrone, naphyrone, flephedrone and butylone were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, i.p.) or methamphetamine (1 mg/kg, i.p.) from saline. All compounds fully substituted for the discriminative stimulus effects of cocaine and methamphetamine. Several commonly marketed cathinones produce discriminative stimulus effects comparable to those of cocaine and methamphetamine, which suggests that these compounds are likely to have similar abuse liability. MDPV and naphyrone produced locomotor stimulant effects that lasted much longer than cocaine or methamphetamine and therefore may be of particular concern, particularly since MDPV is one of the most commonly found substances associated with emergency room visits due to adverse effects from taking “bath salts”. PMID:23839026

  15. Site-specific postural and locomotor changes evoked in awake, freely moving intact cats by stimulating the brainstem.

    PubMed

    Mori, S; Sakamoto, T; Ohta, Y; Takakusaki, K; Matsuyama, K

    1989-12-25

    Locomotor behaviors evoked by stimulating the hypothalamus and the brainstem were studied in freely moving, awake cats. To do this, stimulating microelectrodes were chronically implanted into the subthalamic locomotor region (SLR) in the lateral hypothalamic area (LHA), the mesencephalic locomotor region (MLR) corresponding to the nucleus cuneiformis, the dorsal tegmental field (DTF) and the ventral tegmental field (VTF) of caudal pons along its midline. After recovery from surgery (2-3 days), open field tests were performed to study stimulus effects upon posture and locomotor movements. The stimuli consisted of pulses of 0.2 ms duration of less than 80 microA delivered at 50 pulses/s for 5-20 s. DTF stimulation resulted in suppression of postural support by the hindlimbs. When the cat was in a standing posture, DTF stimulation simply resulted in a sequential alteration of posture to a squatting and then to a final lying posture. In contrast, VTF stimulation evoked an almost opposite series of postural changes to those induced by DTF stimulation. With VTF stimulation, the cat changed from a lying or a squatting position, and then started to walk during continuation of the stimulation. With MLR stimulation, the cat invariably exhibited fast walking and then running movements. It ran straight forward, avoiding collision with walls or other obstacles, and even tried to jump over a fence placed in front of it. With LHA stimulation, the cat started to walk slowly extending its head forward and looking around repeatedly. It tended to walk with a stoop and stealthy steps along the corners of the room. Induced postural and locomotor changes were always accompanied by behavioral arousal reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2611678

  16. Functional Electrical Stimulation Alters the Postural Component of Locomotor Activity in Healthy Humans

    PubMed Central

    Talis, Vera; Ballay, Yves; Grishin, Alexander; Pozzo, Thierry

    2015-01-01

    Knowledge of the effects of Functional Electrical Stimulation (FES) of different intensity on postural stability during walking in healthy subjects is necessary before these relationships in patients with postural disorders can be assessed and understood. We examined healthy subjects in Control group walking on a treadmill for 40 min and in FES group—provided with 30 min of stimulation, which intensity increased every 10 min. The main difference between Control and FES group was the progressive increase of trunk oscillations in sagittal, frontal, and horizontal planes and an increase of relative stance duration in parallel with FES intensity increase. Both Control and FES groups exhibited shank elevation angle increase as an after-effect. It is concluded, that high intensity FES significantly changes the postural component of locomotor activity, but the fatigue signs afterwards were not FES specific. PMID:26733791

  17. Intraspinal micro stimulation generates locomotor-like and feedback-controlled movements.

    PubMed

    Mushahwar, Vivian K; Gillard, Deborah M; Gauthier, Michel J A; Prochazka, Arthur

    2002-03-01

    Intraspinal microstimulation (ISMS) may provide a means for improving motor function in people suffering from spinal cord injuries, head trauma, or stroke. The goal of this study was to determine whether microstimulation of the mammalian spinal cord could generate locomotor-like stepping and feedback-controlled movements of the hindlimbs. Under pentobarbital anesthesia, 24 insulated microwires were implanted in the lumbosacral cord of three adult cats. The cats were placed in a sling leaving all limbs pendent. Bilateral alternating stepping of the hindlimbs was achieved by stimulating through as few as two electrodes in each side of the spinal cord. Typical stride lengths were 23.5 cm, and ample foot clearance was achieved during swing. Mean ground reaction force during stance was 36.4 N, sufficient for load-bearing. Feedback-controlled movements of the cat's foot were achieved by reciprocally modulating the amplitude of stimuli delivered through two intraspinal electrodes generating ankle flexion and extension such that the distance between a sensor on the cat's foot and a free sensor moved back and forth by the investigators was minimized. The foot tracked the displacements of the target sensor through its normal range of motion. Stimulation through electrodes with tips in or near lamina IX elicited movements most suitable for locomotion. In chronically implanted awake cats, stimulation through dorsally located electrodes generated paw shakes and flexion-withdrawals consistent with sensory perception but no weight-bearing extensor movements. These locations would not be suitable for ISMS in incomplete spinal cord injuries. Despite the complexity of the spinal neuronal networks, our results demonstrate that by stimulating through a few intraspinal microwires, near-normal bipedal locomotor-like stepping and feedback-controlled movements could be achieved. PMID:12173741

  18. Dynamics of locomotor activity and heat production in rats after acute stress.

    PubMed

    Pertsov, S S; Alekseeva, I V; Koplik, E V; Sharanova, N E; Kirbaeva, N V; Gapparov, M M G

    2014-05-01

    The dynamics of locomotor activity and heat production were studied in rats demonstrating passive and active behavior in the open field test at different time after exposure to acute emotional stress caused by 12-h immobilization during dark hours. The most pronounced changes in behavior and heat production followed by disturbances in circadian rhythms of these parameters were detected within the first 2 days after stress. In contrast to behaviorally active rats, the most significant decrease in locomotor activity and heat production of passive animals subjected to emotional stress was observed during dark hours. Circadian rhythms of behavior and heat production in rats tended to recover on day 3 after immobilization stress. These data illustrate the specificity of metabolic and behavioral changes reflecting the shift of endogenous biological rhythms in individuals with different prognostic resistance to stress at different terms after exposure to negative emotiogenic stimuli. PMID:24906959

  19. Effect of 1 GeV/n Fe particles on cocaine-stimulated locomotor activity

    NASA Astrophysics Data System (ADS)

    Vazquez, M.; Bruneus, M.; Gatley, J.; Russell, S.; Billups, A.

    Space travel beyond the Earth's protective magnetic field (for example, to Mars) will involve exposure of astronauts to irradiation by high-energy nuclei such as 56Fe (HZE radiation), which are a component of galactic cosmic rays. These particles have high linear energy transfer (LET) and are expected to irreversibly damage cells they traverse. Our working hypothesis is that long-term behavioral alterations are induced after exposure of the brain to 1 GeV/n iron particles with fluences of 1 to 8 particles/cell targets. Previous studies support this notion but are not definitive, especially with regard to long-term effects. Using the Alternating Gradient Synchrotron (AGS) we expose C57 mice to 1 GeV/n 56Fe radiation (head only) at doses of 0, 15, 30, 60, 120 and 240 cGy. There were originally 19 mice per group. The ability of cocaine to increase locomotor activity in 16 of these animals in response to an intraperitoneal injection of cocaine has been measured so far at 1, 4, 8, 12, 16, 20, 24 and 28 weeks. Cocaine-stimulated locomotor activity was chosen in part because it is a behavioral assay with which we have considerable experience. More importantly, the ability to respond to cocaine is a complex behavior involving many neurotransmitter systems and brain circuits. Therefore, the probability of alteration of this behavior by HZE particles was considered high. However, the central circuit is the nigrostriatal dopamine system, in which dopamine is released in striatum from nerve terminals whose cell bodies are located in the substantia nigra. Cocaine activates behavior by blocking dopamine transporters on striatal nerve terminals and therefore elevating the concentration of dopamine in the synapse. Dopamine activates receptors on striatal GABAergic cells that project via other brain regions to the thalamus. Activation of the motor cortex by glutamatergic projections from the thalamus leads ultimately to increased locomotion. The experimental paradigm involves

  20. Acute effects of ethanol or d-amphetamine on the locomotor activity of larval zebrafish in a microtiter plate format.

    EPA Science Inventory

    As part of an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae. We are assessing the acute effects of prototypic drugs that are known to act on the central ...

  1. Optic flow improves adaptability of spatiotemporal characteristics during split-belt locomotor adaptation with tactile stimulation.

    PubMed

    Eikema, Diderik Jan A; Chien, Jung Hung; Stergiou, Nicholas; Myers, Sara A; Scott-Pandorf, Melissa M; Bloomberg, Jacob J; Mukherjee, Mukul

    2016-02-01

    Human locomotor adaptation requires feedback and feed-forward control processes to maintain an appropriate walking pattern. Adaptation may require the use of visual and proprioceptive input to decode altered movement dynamics and generate an appropriate response. After a person transfers from an extreme sensory environment and back, as astronauts do when they return from spaceflight, the prolonged period required for re-adaptation can pose a significant burden. In our previous paper, we showed that plantar tactile vibration during a split-belt adaptation task did not interfere with the treadmill adaptation however, larger overground transfer effects with a slower decay resulted. Such effects, in the absence of visual feedback (of motion) and perturbation of tactile feedback, are believed to be due to a higher proprioceptive gain because, in the absence of relevant external dynamic cues such as optic flow, reliance on body-based cues is enhanced during gait tasks through multisensory integration. In this study, we therefore investigated the effect of optic flow on tactile-stimulated split-belt adaptation as a paradigm to facilitate the sensorimotor adaptation process. Twenty healthy young adults, separated into two matched groups, participated in the study. All participants performed an overground walking trial followed by a split-belt treadmill adaptation protocol. The tactile group (TC) received vibratory plantar tactile stimulation only, whereas the virtual reality and tactile group (VRT) received an additional concurrent visual stimulation: a moving virtual corridor, inducing perceived self-motion. A post-treadmill overground trial was performed to determine adaptation transfer. Interlimb coordination of spatiotemporal and kinetic variables was quantified using symmetry indices and analyzed using repeated-measures ANOVA. Marked changes of step length characteristics were observed in both groups during split-belt adaptation. Stance and swing time symmetries were

  2. Nanomolar Oxytocin Synergizes with Weak Electrical Afferent Stimulation to Activate the Locomotor CPG of the Rat Spinal Cord In Vitro

    PubMed Central

    Dose, Francesco; Zanon, Patrizia; Coslovich, Tamara; Taccola, Giuliano

    2014-01-01

    Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM–1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other

  3. Brain Stimulation Paired with Novel Locomotor Training with Robotic Gait Orthosis in Chronic Stroke: a Feasibility Study

    PubMed Central

    Danzl, Megan M.; Chelette, Kenneth C.; Lee, Kara; Lykins, Dana; Sawaki, Lumy

    2015-01-01

    Objectives 1) to investigate the feasibility of combining transcranial direct current stimulation (tDCS) to the lower extremity (LE) motor cortex with novel locomotor training to facilitate gait in subjects with chronic stroke and low ambulatory status, and 2) to obtain insight from study subjects and their caregivers to inform future trial design. Methods Double-blind, randomized controlled study with additional qualitative exploratory descriptive design. One-month follow-up.10 subjects with stroke were recruited and randomized to active tDCS or sham tDCS for 12 sessions. Both groups participated in identical locomotor training with a robotic gait orthosis (RGO) following each tDCS session. RGO training protocol was designed to harness cortical neuroplasticity. Data analysis included assessment of functional and participation outcome measures and qualitative thematic analysis. Results Eight subjects completed the study. Both groups demonstrated trends toward improvement, but the active tDCS group showed greater improvement than the sham group. Qualitative analyses indicate beneficial effects of this combined intervention. Conclusions It is feasible to combine tDCS targeting the LE motor cortex with our novel locomotor training. It appears that tDCS has the potential to enhance the effectiveness of gait training in chronic stroke. Insights from participants provide additional guidance in designing future trials. PMID:23949035

  4. Relationships between locomotor activation and alterations in brain temperature during selective blockade and stimulation of dopamine transmission.

    PubMed

    Brown, P L; Bae, D; Kiyatkin, E A

    2007-03-01

    It is well known that the dopamine (DA) system plays an essential role in the organization and regulation of brain activational processes. Various environmental stimuli that induce locomotor activation also increase DA transmission, while DA antagonists decrease spontaneous locomotion. Our previous work supports close relationships between locomotor activation and brain and body temperature increases induced by salient environmental challenges or occurring during motivated behavior. While this correlation was also true for psychomotor stimulant drugs such as methamphetamine and MDMA, more complex relationships or even inverted correlations were found for other drugs that are known to increase DA transmission (i.e. heroin and cocaine). In the present study we examined brain, muscle and skin temperatures together with conventional locomotion during selective interruption of DA transmission induced by a mixture of D1 and D2 antagonists (SCH-23390 and eticlopride at 0.2 mg/kg, s.c.) and its selective activation by apomorphine (APO; 0.05 and 0.25 mg/kg, i.v.) in rats. While full DA receptor blockade decreased spontaneous locomotion, it significantly increased brain, muscle and skin temperatures, suggesting metabolic brain activation under conditions of vasodilatation (or weakening of normal vascular tone). In contrast, APO strongly decreased skin temperature but tended to decrease brain and muscle temperatures despite strong hyperlocomotion and stereotypy. The brain temperature response to APO was strongly dependent on basal brain temperature, with hypothermia at high basal temperatures and weak hyperthermia at low temperatures. While supporting the role of DA in locomotor activation, these data suggest more complex relationships between drug-induced alterations in DA transmission, behavioral activation and metabolic brain activation. PMID:17196751

  5. Interactions between Dorsal and Ventral Root Stimulation on the Generation of Locomotor-Like Activity in the Neonatal Mouse Spinal Cord.

    PubMed

    Pujala, Avinash; Blivis, Dvir; O'Donovan, Michael J

    2016-01-01

    We investigated whether dorsal (DR) and ventral root (VR) stimulus trains engage common postsynaptic components to activate the central pattern generator (CPG) for locomotion in the neonatal mouse spinal cord. VR stimulation did not activate the first order interneurons mediating the activation of the locomotor CPG by sacrocaudal afferent stimulation. Simultaneous stimulation of adjacent dorsal or ventral root pairs, subthreshold for evoking locomotor-like activity, did not summate to activate the CPG. This suggests that locomotor-like activity is triggered when a critical class of efferent or afferent axons is stimulated and does not depend on the number of stimulated axons or activated postsynaptic neurons. DR- and VR-evoked episodes exhibited differences in the coupling between VR pairs. In DR-evoked episodes, the coupling between the ipsilateral and contralateral flexor/extensor roots was similar and stronger than the bilateral extensor roots. In VR-evoked episodes, ipsilateral flexor/extensor coupling was stronger than both the contralateral flexor/extensor and the bilateral extensor coupling. For both types of stimulation, the coupling was greatest between the bilateral L1/L2 flexor-dominated roots. This indicates that the recruitment and/or the firing pattern of motoneurons differed in DR and VR-evoked episodes. However, the DR and VR trains do not appear to activate distinct CPGs because trains of DR and VR stimuli at frequencies too low to evoke locomotor-like activity did so when they were interleaved. These results indicate that the excitatory actions of VR stimulation converge onto the CPG through an unknown pathway that is not captured by current models of the locomotor CPG. PMID:27419215

  6. Interactions between Dorsal and Ventral Root Stimulation on the Generation of Locomotor-Like Activity in the Neonatal Mouse Spinal Cord

    PubMed Central

    2016-01-01

    Abstract We investigated whether dorsal (DR) and ventral root (VR) stimulus trains engage common postsynaptic components to activate the central pattern generator (CPG) for locomotion in the neonatal mouse spinal cord. VR stimulation did not activate the first order interneurons mediating the activation of the locomotor CPG by sacrocaudal afferent stimulation. Simultaneous stimulation of adjacent dorsal or ventral root pairs, subthreshold for evoking locomotor-like activity, did not summate to activate the CPG. This suggests that locomotor-like activity is triggered when a critical class of efferent or afferent axons is stimulated and does not depend on the number of stimulated axons or activated postsynaptic neurons. DR- and VR-evoked episodes exhibited differences in the coupling between VR pairs. In DR-evoked episodes, the coupling between the ipsilateral and contralateral flexor/extensor roots was similar and stronger than the bilateral extensor roots. In VR-evoked episodes, ipsilateral flexor/extensor coupling was stronger than both the contralateral flexor/extensor and the bilateral extensor coupling. For both types of stimulation, the coupling was greatest between the bilateral L1/L2 flexor-dominated roots. This indicates that the recruitment and/or the firing pattern of motoneurons differed in DR and VR-evoked episodes. However, the DR and VR trains do not appear to activate distinct CPGs because trains of DR and VR stimuli at frequencies too low to evoke locomotor-like activity did so when they were interleaved. These results indicate that the excitatory actions of VR stimulation converge onto the CPG through an unknown pathway that is not captured by current models of the locomotor CPG. PMID:27419215

  7. Effects of the imidazobenzodiazepine R015-4513 on the stimulant and depressant actions of ethanol on spontaneous locomotor activity

    SciTech Connect

    Becker, H.C.

    1988-01-01

    The purpose of this study was to investigate the effects of the imidazobenzodiazepine R015-4513, a partial inverse agonist at benzodiazepine (BDZ) receptors, on the stimulant and depressant actions of ethanol in mice. For comparative purposes, another BDZ inverse agonist, FG-7142, was examined as well. Neither R015-4513 nor FG-7142 influenced the low-dose excitatory effects of ethanol on spontaneous locomotor activity. However, both R015-4513 and FG-7142 significantly antagonized the depressant effects of ethanol, and this antagonism was completely reversed by pretreatment with the BDZ receptor antagonist, R015-1788. These data suggest that R015-4513 is capable of antagonizing only some of the behavioral effects of ethanol, and in particular, those responses to ethanol that are mediated by modulation of the GABA/BDZ-chloride channel receptor complex.

  8. Amphetamine locomotor sensitization is accompanied with an enhanced high K⁺-stimulated Dopamine release in the rat medial prefrontal cortex.

    PubMed

    Casanova, José Patricio; Velis, Gabriela Paz; Fuentealba, José Antonio

    2013-01-15

    In the present work, we assessed dopamine extracellular levels in the medial Prefrontal Cortex of rats repeatedly treated with amphetamine during early abstinence. Rats were injected once daily with amphetamine for five consecutive days. A sensitized locomotor response was observed in 55% of animals treated. After two days of abstinence, an amphetamine challenge dose was given to all rats and locomotor activity was measured to assess expression of sensitization. A persistence of heightened locomotor response to amphetamine was observed in rats that developed sensitization. Twenty four hours after amphetamine challenge, microdialysis experiments were carried out to evaluate basal and stimulated dopamine extracellular levels in the medial Prefrontal Cortex. Rats that developed and expressed amphetamine locomotor sensitization showed a significantly greater high potassium-stimulated dopamine release compared to Non-sensitized and Saline rats. These results show that the increased dopamine releasability in the medial Prefrontal Cortex occurs soon after development of amphetamine locomotor sensitization, and might be underlying the early expression of sensitization. PMID:23047059

  9. The Effects of Acute Exposure to Neuroactive Drugs on the Locomotor Activity of Larval Zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae using prototypic drugs that act on the central nervous system. Initially, we chose to define the beh...

  10. Comparison of (+)- and (-)-Naloxone on the Acute Psychomotor-Stimulating Effects of Heroin, 6-Acetylmorphine, and Morphine in Mice.

    PubMed

    Eriksen, Guro Søe; Andersen, Jannike Mørch; Boix, Fernando; Bergh, Marianne Skov-Skov; Vindenes, Vigdis; Rice, Kenner C; Huestis, Marilyn A; Mørland, Jørg

    2016-08-01

    Toll-like receptor 4 (TLR4) signaling is implied in opioid reinforcement, reward, and withdrawal. Here, we explored whether TLR4 signaling is involved in the acute psychomotor-stimulating effects of heroin, 6-acetylmorphine (6-AM), and morphine as well as whether there are differences between the three opioids regarding TLR4 signaling. To address this, we examined how pretreatment with (+)-naloxone, a TLR4 active but opioid receptor (OR) inactive antagonist, affected the acute increase in locomotor activity induced by heroin, 6-AM, or morphine in mice. We also assessed the effect of pretreatment with (-)-naloxone, a TLR4 and OR active antagonist, as well as the pharmacokinetic profiles of (+) and (-)-naloxone in the blood and brain. We found that (-)-naloxone reduced acute opioid-induced locomotor activity in a dose-dependent manner. By contrast, (+)-naloxone, administered in doses assumed to antagonize TLR4 but not ORs, did not affect acute locomotor activity induced by heroin, 6-AM, or morphine. Both naloxone isomers exhibited similar concentration versus time profiles in the blood and brain, but the brain concentrations of (-)-naloxone reached higher levels than those of (+)-naloxone. However, the discrepancies in their pharmacokinetic properties did not explain the marked difference between the two isomers' ability to affect opioid-induced locomotor activity. Our results underpin the importance of OR activation and do not indicate an apparent role of TLR4 signaling in acute opioid-induced psychomotor stimulation in mice. Furthermore, there were no marked differences between heroin, 6-AM, and morphine regarding involvement of OR or TLR4 signaling. PMID:27278234

  11. Acute molecular response of mouse hindlimb muscles to chronic stimulation

    PubMed Central

    Jayaraman, R. C.; Bombach, K. L.; Ankrapp, D. P.; Krill-Burger, J. M.; Sciulli, C. M.; Petrosko, P.; Wiseman, R. W.

    2009-01-01

    Stimulation of the mouse hindlimb via the sciatic nerve was performed for a 4-h period to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 ± 0.1 g/g body wt) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon study completion. An immediate-early growth response was present in the extensor digitorum longus (EDL) muscle (FOS, JUN, activating transcription factor 3, and musculoaponeurotic fibrosarcoma oncogene) with a similar but attenuated pattern in the soleus muscle. Transcript profiles showed decreased fast fiber-specific mRNA (myosin heavy chains 2A and 2B, fast troponins T3 and I, α-tropomyosin, muscle creatine kinase, and parvalbumin) and increased slow transcripts (myosin heavy chain-1β/slow, troponin C slow, and tropomyosin 3y) in the EDL versus soleus muscles. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration in stimulated versus control muscles, whereas ultrastructural analysis showed no evidence of myofiber damage after stimulation. Multiple fiber type-specific transcription factors (tea domain family member 1, nuclear factor of activated T cells 1, peroxisome proliferator-activated receptor-γ coactivator-1α and -β, circadian locomotor output cycles kaput, and hypoxia-inducible factor-1α) increased in the EDL along with transcription factors characteristic of embryogenesis (Kruppel-like factor 4; SRY box containing 17; transcription factor 15; PBX/knotted 1 homeobox 1; and embryonic lethal, abnormal vision). No established in vivo satellite cell markers or genes activated in our parallel experiments of satellite cell proliferation in vitro (cyclins A2, B2, C, and E1 and MyoD) were differentially increased in the stimulated muscles. These results indicated that the molecular onset of fast to slow phenotype conversion occurred in the EDL within 4 h of stimulation

  12. Dopamine transporter occupancy by RTI-55, inhibition of dopamine transport and stimulation of locomotor activity

    SciTech Connect

    Gatley, S.J.; Gifford, A.N.; Volkow, N.D.

    1997-05-01

    Cocaine analogs such as RTI-55 (or {beta}CIT) with a higher affinity for the DAT are potentially useful as therapeutic drugs in cocaine abuse as well as for radiopharmaceutical use. Previously we showed that in mice RTI-55 (2 mg/Kg, i/p) reduced H-3 cocaine striatum-to-cerebellum ratios (St/Cb, {lg_bullet}) from 1.6 to 1.2 at 3 h after administration, with recovery by 12 h. In the present study we demonstrate a very similar time-course for transport {triangle} measured in striatal homo within 2 min of sacrifice. The maximum inhibition of uptake at about 1 h corresponded to about 80% of the control uptake rate, similar to the percent reduction in St/Cb. The time-course of the effect of this dose of RTI-55 on locomotor activity ({sq_bullet}) was complex, with a drop in the activity measure at 7 h, after a further injection of RTI-55, but activity remained higher than in saline controls. In spite of this complexity, which may be associated with stereotypies and/or exhaustion, the duration of increased activity is consistent with the duration of transporter blockade. These experiments support the notion that PET/SPECT measures of transporter occupancy accurately reflect transporter inhibition.

  13. Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone)*

    PubMed Central

    Miller, M. L.; Creehan, K.M.; Angrish, D.; Barlow, D. J.; Houseknecht, K. L.; Dickerson, T. J.; Taffe, M. A.

    2012-01-01

    BACKGROUND The substituted cathinone compound known as mephedrone (4-methylmethcathinone; 4-MMC) has become popular with recreational users of psychomotor-stimulant compounds. Only recently have the first preclinical studies provided information about this drug in the scientific literature; nevertheless, media reports have led to drug control actions in the UK and across several US states. Rodent studies indicate that 4-MMC exhibits neuropharmacological similarity to 3,4-methylenedioxymethamphetamine (MDMA) and prompt investigation of the thermoregulatory, cardiac and locomotor effects of 4-MMC. This study focuses on the role of ambient temperature, which has been shown to shift the effects of MDMA from hyperthermic to hypothermic. METHODS Male Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1.0–5.6 mg/kg) using an implantable radiotelemetry system under conditions of low (20°C) and high (30°C) ambient temperature. A pharmacokinetic study found a Tmax of 0.25 h and a Cmax of 1,206 ng/mL after 5.6 mg/kg 4-MMC. A dose-dependent reduction of body temperature was produced by 4-MMC at 20°C but there was no temperature change at 30°C. RESULTS Increased locomotor activity was observed after 4-MMC administration under both ambient temperatures, however, significantly more activity was observed at 30°C. Heart rate was slowed by 1.0 and 5.6 mg/kg 4-MMC at 20°C, and was slower in the 30°C vs. 20°C condition across all treatments. CONCLUSION These results show that the cathinone analog 4-MMC exhibits in vivo thermoregulatory properties that are distinct from those produced by MDMA. PMID:22832282

  14. The Anorexigenic Peptide Neuromedin U (NMU) Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice.

    PubMed

    Vallöf, Daniel; Vestlund, Jesper; Engel, Jörgen A; Jerlhag, Elisabet

    2016-01-01

    Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc) suggesting that these brain areas are important for reward. The physiological function of gut-brain peptides has expanded beyond food intake modulation and involves regulation of drug reinforcement. A novel candidate for reward regulation is the anorexigenic peptide neuromedin U (NMU). We therefore investigated the effects of intracerebroventricular (icv) administration of NMU on amphetamine's well-documented effects on the mesoaccumbal dopamine system, i.e. locomotor stimulation and accumbal dopamine release in mice. In addition, the effect of accumbal NMU administration on locomotor activity was examined. The effect of NMU, icv or intra-NAc, on the expression of conditioned place preference (CPP) was elucidated. Firstly, we showed that icv administration of NMU attenuate the amphetamine-induced locomotor stimulation, accumbal dopamine release and expression of CPP in mice. Secondly, we found that a lower dose of NMU (icv) reduce the amphetamine-induced locomotor stimulation in mice. Thirdly, we demonstrated that NMU administration into the NAc block the ability of amphetamine to cause a locomotor stimulation in mice. However, accumbal NMU administration did not attenuate the amphetamine-induced expression of CPP in mice. Our novel data suggest that central NMU signalling is involved in development of amphetamine dependence. PMID:27139195

  15. The Anorexigenic Peptide Neuromedin U (NMU) Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice

    PubMed Central

    Vallöf, Daniel; Vestlund, Jesper; Engel, Jörgen A.; Jerlhag, Elisabet

    2016-01-01

    Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc) suggesting that these brain areas are important for reward. The physiological function of gut-brain peptides has expanded beyond food intake modulation and involves regulation of drug reinforcement. A novel candidate for reward regulation is the anorexigenic peptide neuromedin U (NMU). We therefore investigated the effects of intracerebroventricular (icv) administration of NMU on amphetamine’s well-documented effects on the mesoaccumbal dopamine system, i.e. locomotor stimulation and accumbal dopamine release in mice. In addition, the effect of accumbal NMU administration on locomotor activity was examined. The effect of NMU, icv or intra-NAc, on the expression of conditioned place preference (CPP) was elucidated. Firstly, we showed that icv administration of NMU attenuate the amphetamine-induced locomotor stimulation, accumbal dopamine release and expression of CPP in mice. Secondly, we found that a lower dose of NMU (icv) reduce the amphetamine-induced locomotor stimulation in mice. Thirdly, we demonstrated that NMU administration into the NAc block the ability of amphetamine to cause a locomotor stimulation in mice. However, accumbal NMU administration did not attenuate the amphetamine-induced expression of CPP in mice. Our novel data suggest that central NMU signalling is involved in development of amphetamine dependence. PMID:27139195

  16. Effects of acute and repeated zolpidem treatment on pentylenetetrazole-induced seizure threshold and on locomotor activity: comparison with diazepam.

    PubMed

    Vlainić, Josipa; Pericić, Danka

    2009-06-01

    Zolpidem and diazepam are widely used drugs acting via benzodiazepine binding sites on GABA(A) receptors. While diazepam is non-selective, zolpidem has a high affinity for alpha1-, and no affinity for alpha5-containing receptors. Several studies suggested that behavioral effects of zolpidem might be more similar to classical benzodiazepines than previously thought. To compare the sedative and anticonvulsant properties of these drugs and to evaluate the importance of GABA(A) receptor subunits for development of tolerance during chronic treatment, we tested the effects of acute and repeated administration of zolpidem and diazepam on ambulatory locomotor activity (a measure of sedation) and on the threshold for myoclonic, clonic and tonic seizures in response to i.v. infusion of pentylenetetrazole (PTZ). Both drugs given acutely in doses 0.3, 1 and 3 mg/kg reduced locomotion, and in doses 1 and 3 mg/kg elevated the threshold for PTZ-induced seizures. The effects of zolpidem and diazepam on the tonic seizure threshold were greater than on myoclonus and clonic seizure threshold. Diazepam and zolpidem (3 mg/kg), given 18 or 42 h after repeated drug treatment (10 days, 5 mg/kg, twice daily), decreased the PTZ seizure threshold and increased the locomotor activity as compared to control mice, indicating development of tolerance to their anticonvulsant and sedative effects. After repeated treatment the PTZ seizure threshold was not different between the two drugs, while differences in sedation became larger than after the acute treatment. The results suggest that alpha5-containing GABA(A) receptors are not crucial for the development of sedative and anticonvulsant tolerance. PMID:19345234

  17. Using low levels of stochastic vestibular stimulation to improve locomotor stability.

    PubMed

    Mulavara, Ajitkumar P; Kofman, Igor S; De Dios, Yiri E; Miller, Chris; Peters, Brian T; Goel, Rahul; Galvan-Garza, Raquel; Bloomberg, Jacob J

    2015-01-01

    Low levels of bipolar binaural white noise based imperceptible stochastic electrical stimulation to the vestibular system (stochastic vestibular stimulation, SVS) have been shown to improve stability during balance tasks in normal, healthy subjects by facilitating enhanced information transfer using stochastic resonance (SR) principles. We hypothesize that detection of time-critical sub-threshold sensory signals using low levels of bipolar binaural SVS based on SR principles will help improve stability of walking during support surface perturbations. In the current study 13 healthy subjects were exposed to short continuous support surface perturbations for 60 s while walking on a treadmill and simultaneously viewing perceptually matched linear optic flow. Low levels of bipolar binaural white noise based SVS were applied to the vestibular organs. Multiple trials of the treadmill locomotion test were performed with stimulation current levels varying in the range of 0-1500 μA, randomized across trials. The results show that subjects significantly improved their walking stability during support surface perturbations at stimulation levels with peak amplitude predominantly in the range of 100-500 μA consistent with the SR phenomenon. Additionally, objective perceptual motion thresholds were measured separately as estimates of internal noise while subjects sat on a chair with their eyes closed and received 1 Hz bipolar binaural sinusoidal electrical stimuli. The optimal improvement in walking stability was achieved on average with peak stimulation amplitudes of approximately 35% of perceptual motion threshold. This study shows the effectiveness of using low imperceptible levels of SVS to improve dynamic stability during walking on a laterally oscillating treadmill via the SR phenomenon. PMID:26347619

  18. Using low levels of stochastic vestibular stimulation to improve locomotor stability

    PubMed Central

    Mulavara, Ajitkumar P.; Kofman, Igor S.; De Dios, Yiri E.; Miller, Chris; Peters, Brian T.; Goel, Rahul; Galvan-Garza, Raquel; Bloomberg, Jacob J.

    2015-01-01

    Low levels of bipolar binaural white noise based imperceptible stochastic electrical stimulation to the vestibular system (stochastic vestibular stimulation, SVS) have been shown to improve stability during balance tasks in normal, healthy subjects by facilitating enhanced information transfer using stochastic resonance (SR) principles. We hypothesize that detection of time-critical sub-threshold sensory signals using low levels of bipolar binaural SVS based on SR principles will help improve stability of walking during support surface perturbations. In the current study 13 healthy subjects were exposed to short continuous support surface perturbations for 60 s while walking on a treadmill and simultaneously viewing perceptually matched linear optic flow. Low levels of bipolar binaural white noise based SVS were applied to the vestibular organs. Multiple trials of the treadmill locomotion test were performed with stimulation current levels varying in the range of 0–1500 μA, randomized across trials. The results show that subjects significantly improved their walking stability during support surface perturbations at stimulation levels with peak amplitude predominantly in the range of 100–500 μA consistent with the SR phenomenon. Additionally, objective perceptual motion thresholds were measured separately as estimates of internal noise while subjects sat on a chair with their eyes closed and received 1 Hz bipolar binaural sinusoidal electrical stimuli. The optimal improvement in walking stability was achieved on average with peak stimulation amplitudes of approximately 35% of perceptual motion threshold. This study shows the effectiveness of using low imperceptible levels of SVS to improve dynamic stability during walking on a laterally oscillating treadmill via the SR phenomenon. PMID:26347619

  19. Inducing hindlimb locomotor recovery in adult rat after complete thoracic spinal cord section using repeated treadmill training with perineal stimulation only

    PubMed Central

    Alluin, Olivier; Delivet-Mongrain, Hugo

    2015-01-01

    Although a complete thoracic spinal cord section in various mammals induces paralysis of voluntary movements, the spinal lumbosacral circuitry below the lesion retains its ability to generate hindlimb locomotion. This important capacity may contribute to the overall locomotor recovery after partial spinal cord injury (SCI). In rats, it is usually triggered by pharmacological and/or electrical stimulation of the cord while a robot sustains the animals in an upright posture. In the present study we daily trained a group of adult spinal (T7) rats to walk with the hindlimbs for 10 wk (10 min/day for 5 days/wk), using only perineal stimulation. Kinematic analysis and terminal electromyographic recordings revealed a strong effect of training on the reexpression of hindlimb locomotion. Indeed, trained animals gradually improved their locomotion while untrained animals worsened throughout the post-SCI period. Kinematic parameters such as averaged and instant swing phase velocity, step cycle variability, foot drag duration, off period duration, and relationship between the swing features returned to normal values only in trained animals. The present results clearly demonstrate that treadmill training alone, in a normal horizontal posture, elicited by noninvasive perineal stimulation is sufficient to induce a persistent hindlimb locomotor recovery without the need for more complex strategies. This provides a baseline level that should be clearly surpassed if additional locomotor-enabling procedures are added. Moreover, it has a clinical value since intrinsic spinal reorganization induced by training should contribute to improve locomotor recovery together with afferent feedback and supraspinal modifications in patients with incomplete SCI. PMID:26203108

  20. Inducing hindlimb locomotor recovery in adult rat after complete thoracic spinal cord section using repeated treadmill training with perineal stimulation only.

    PubMed

    Alluin, Olivier; Delivet-Mongrain, Hugo; Rossignol, Serge

    2015-09-01

    Although a complete thoracic spinal cord section in various mammals induces paralysis of voluntary movements, the spinal lumbosacral circuitry below the lesion retains its ability to generate hindlimb locomotion. This important capacity may contribute to the overall locomotor recovery after partial spinal cord injury (SCI). In rats, it is usually triggered by pharmacological and/or electrical stimulation of the cord while a robot sustains the animals in an upright posture. In the present study we daily trained a group of adult spinal (T7) rats to walk with the hindlimbs for 10 wk (10 min/day for 5 days/wk), using only perineal stimulation. Kinematic analysis and terminal electromyographic recordings revealed a strong effect of training on the reexpression of hindlimb locomotion. Indeed, trained animals gradually improved their locomotion while untrained animals worsened throughout the post-SCI period. Kinematic parameters such as averaged and instant swing phase velocity, step cycle variability, foot drag duration, off period duration, and relationship between the swing features returned to normal values only in trained animals. The present results clearly demonstrate that treadmill training alone, in a normal horizontal posture, elicited by noninvasive perineal stimulation is sufficient to induce a persistent hindlimb locomotor recovery without the need for more complex strategies. This provides a baseline level that should be clearly surpassed if additional locomotor-enabling procedures are added. Moreover, it has a clinical value since intrinsic spinal reorganization induced by training should contribute to improve locomotor recovery together with afferent feedback and supraspinal modifications in patients with incomplete SCI. PMID:26203108

  1. Effect of Ambient Temperature on the Thermoregulatory and Locomotor Stimulant Effects of 4-Methylmethcathinone in Wistar and Sprague-Dawley Rats

    PubMed Central

    Wright, M. Jerry; Angrish, Deepshikha; Aarde, Shawn M.; Barlow, Deborah J.; Buczynski, Matthew W.; Creehan, Kevin M.; Vandewater, Sophia A.; Parsons, Loren H.; Houseknecht, Karen L.; Dickerson, Tobin J.; Taffe, Michael A.

    2012-01-01

    The drug 4-methylmethcathinone (4-MMC; aka, mephedrone, MMCAT, “plant food”, “bath salts”) is a recent addition to the list of popular recreational psychomotor-stimulant compounds. Relatively little information about this drug is available in the scientific literature, but popular media reports have driven recent drug control actions in the UK and several US States. Online user reports of subjective similarity to 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) prompted the current investigation of the thermoregulatory and locomotor effects of 4-MMC. Male Wistar and Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1–10 mg/kg ) using an implantable radiotelemetry system under conditions of low (23°C) and high (27°C) ambient temperature. A reliable reduction of body temperature was produced by 4-MMC in Wistar rats at 23°C or 27°C with only minimal effect in Sprague-Dawley rats. Increased locomotor activity was observed after 4-MMC administration in both strains with significantly more activity produced in the Sprague-Dawley strain. The 10 mg/kg s.c. dose evoked greater increase in extracellular serotonin, compared with dopamine, in the nucleus accumbens. Follow-up studies confirmed that the degree of locomotor stimulation produced by 10 mg/kg 4-MMC was nearly identical to that produced by 1 mg/kg d-methamphetamine in each strain. Furthermore, hypothermia produced by the serotonin 1A/7 receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) was similar in each strain. These results show that the cathinone analog 4-MMC exhibits thermoregulatory and locomotor properties that are distinct from those established for methamphetamine or MDMA in prior work, despite recent evidence of neuropharmacological similarity with MDMA. PMID:22952999

  2. The Glucagon-Like Peptide 1 Analogue Exendin-4 Attenuates the Nicotine-Induced Locomotor Stimulation, Accumbal Dopamine Release, Conditioned Place Preference as well as the Expression of Locomotor Sensitization in Mice

    PubMed Central

    Egecioglu, Emil; Engel, Jörgen A.; Jerlhag, Elisabet

    2013-01-01

    The gastrointestinal peptide glucagon-like peptide 1 (GLP-1) is known to regulate consummatory behavior and is released in response to nutrient ingestion. Analogues of this peptide recently emerged as novel pharmacotherapies for treatment of type II diabetes since they reduce gastric emptying, glucagon secretion as well as enhance glucose-dependent insulin secretion. The findings that GLP-1 targets reward related areas including mesolimbic dopamine areas indicate that the physiological role of GLP-1 extends beyond food intake and glucose homeostasis control to include reward regulation. The present series of experiments was therefore designed to investigate the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4), on established nicotine-induced effects on the mesolimbic dopamine system in mice. Specifically, we show that treatment with Ex4, at a dose with no effect per se, attenuate nicotine-induced locomotor stimulation, accumbal dopamine release as well as the expression of conditioned place preference in mice. In accordance, Ex4 also blocks nicotine-induced expression of locomotor sensitization in mice. Given that development of nicotine addiction largely depends on the effects of nicotine on the mesolimbic dopamine system these findings indicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for nicotine cessations in humans. PMID:24204788

  3. Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CpG of the rat spinal cord in vitro.

    PubMed

    Dose, Francesco; Zanon, Patrizia; Coslovich, Tamara; Taccola, Giuliano

    2014-01-01

    Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other

  4. Effects of acute and repeated administration of N-methyl-D-aspartate (NMDA) into the ventral tegmental area: locomotor activating effects of NMDA and cocaine.

    PubMed

    Schenk, S; Partridge, B

    1997-09-26

    Repeated, intermittent administration of psychostimulants produces an enhancement of the subsequent behavioral effects of these drugs. This behavioral sensitization has been implicated in maintenance of and relapse to drug-taking. As a result, there has been great interest in elucidating the mechanisms underlying both the development and expression of sensitization. An accumulation of data from studies of stimulant-induced locomotor activity has implicated excitatory amino acids in the development of behavioral sensitization. In the present study, N-methyl-D-aspartate (NMDA) (0.6, 1.25 or 2.5 microg) infused bilaterally into the ventral tegmental area (VTA) produced dose-dependent locomotor activation. The locomotor activating effect of NMDA was increased following repeated NMDA administration (two exposures to intra-VTA NMDA), suggesting sensitization. However, repeated intra-VTA NMDA failed to sensitize rats to the locomotor activating effects of systemically administered cocaine (5.0, 10.0 or 20.0 mg/kg). These findings are consistent with the notion that repeated activation of NMDA receptors is sufficient for the development of behavioral sensitization to NMDA. Other neuroadaptations produced by repeated psychostimulant administration are required in order for the development of sensitization to the behavioral effects of those drugs. PMID:9374190

  5. Comparison of (+)- and (−)-Naloxone on the Acute Psychomotor-Stimulating Effects of Heroin, 6-Acetylmorphine, and Morphine in Mice

    PubMed Central

    Andersen, Jannike Mørch; Boix, Fernando; Bergh, Marianne Skov-Skov; Vindenes, Vigdis; Rice, Kenner C.; Huestis, Marilyn A.; Mørland, Jørg

    2016-01-01

    Toll-like receptor 4 (TLR4) signaling is implied in opioid reinforcement, reward, and withdrawal. Here, we explored whether TLR4 signaling is involved in the acute psychomotor-stimulating effects of heroin, 6-acetylmorphine (6-AM), and morphine as well as whether there are differences between the three opioids regarding TLR4 signaling. To address this, we examined how pretreatment with (+)-naloxone, a TLR4 active but opioid receptor (OR) inactive antagonist, affected the acute increase in locomotor activity induced by heroin, 6-AM, or morphine in mice. We also assessed the effect of pretreatment with (−)-naloxone, a TLR4 and OR active antagonist, as well as the pharmacokinetic profiles of (+) and (−)-naloxone in the blood and brain. We found that (−)-naloxone reduced acute opioid-induced locomotor activity in a dose-dependent manner. By contrast, (+)-naloxone, administered in doses assumed to antagonize TLR4 but not ORs, did not affect acute locomotor activity induced by heroin, 6-AM, or morphine. Both naloxone isomers exhibited similar concentration versus time profiles in the blood and brain, but the brain concentrations of (−)-naloxone reached higher levels than those of (+)-naloxone. However, the discrepancies in their pharmacokinetic properties did not explain the marked difference between the two isomers’ ability to affect opioid-induced locomotor activity. Our results underpin the importance of OR activation and do not indicate an apparent role of TLR4 signaling in acute opioid-induced psychomotor stimulation in mice. Furthermore, there were no marked differences between heroin, 6-AM, and morphine regarding involvement of OR or TLR4 signaling. PMID:27278234

  6. Brief light stimulation during the mouse nocturnal activity phase simultaneously induces a decline in core temperature and locomotor activity followed by EEG-determined sleep

    PubMed Central

    Studholme, Keith M.; Gompf, Heinrich S.

    2013-01-01

    Light exerts a variety of effects on mammals. Unexpectedly, one of these effects is the cessation of nocturnal locomotion and the induction of behavioral sleep (photosomnolence). Here, we extend the initial observations in several ways, including the fundamental demonstration that core body temperature (Tc) drops substantially (about 1.5°C) in response to the light stimulation at CT15 or CT18 in a manner suggesting that the change is a direct response to light rather than simply a result of the locomotor suppression. The results show that 1) the decline of locomotion and Tc begin soon after nocturnal light stimulation; 2) the variability in the magnitude and onset of light-induced locomotor suppression is very large, whereas the variability in Tc is very small; 3) Tc recovers from the light-induced decline in advance of the recovery of locomotion; 4) under entrained and freerunning conditions, the daily late afternoon Tc increase occurs in advance of the corresponding increase in wheel running; and 5) toward the end of the subjective night, the nocturnally elevated Tc persists longer than does locomotor activity. Finally, EEG measurements confirm light-induced sleep and, when Tc or locomotion was measured, show their temporal association with sleep onset. Both EEG- and immobility-based sleep detection methods confirm rapid induction of light-induced sleep. The similarities between light-induced loss of locomotion and drop in Tc suggest a common cause for parallel responses. The photosomnolence response may be contingent upon both the absence of locomotion and a simultaneous low Tc. PMID:23364525

  7. 3-Methoxynaltrexone is not a selective antagonist for the acute psychomotor stimulating effects of heroin and 6-monoacetylmorphine in mice.

    PubMed

    Eriksen, Guro Søe; Andersen, Jannike Mørch; Boix, Fernando; Mørland, Jørg

    2014-07-01

    The opioid receptor antagonist 3-methoxynaltrexone (3-MeONtx) has previously been shown in rodents to selectively reverse the analgesic actions of heroin and its metabolites 6-monoacetylmorphine (6-MAM), and morphine-6-glucuronide (M6G), but not that of morphine. Based on these and other results, a heroin/6-MAM/M6G μ-opioid receptor binding site or subreceptor mediating their analgesic activity has been proposed. It is however unknown whether this also accounts for the acute psychomotor stimulating properties of these opioids. The aim of the present study was therefore to explore if the acute psychomotor stimulating effects of heroin, 6-MAM, and morphine are mediated by distinct μ-opioid receptor binding sites or subreceptors. To address this aim, we examined how pretreatment with 3-MeONtx or naltrexone (NTX) affected the acute increase in locomotor activity induced by heroin, 6-MAM, or morphine in mice. The pharmacokinetic profiles of 3-MeONtx and NTX were also assessed in mouse brain. We found that 3-MeONtx similarly antagonized the acute increase in locomotor activity induced by equipotent doses of heroin, 6-MAM, or morphine. This antagonistic effect was comparable to the one observed following administration of NTX, and both antagonists gave similar pharmacokinetic profiles in mouse brain. Our findings do not support that different μ-opioid receptor subtypes or a distinct binding site at the μ-opioid receptor is involved in morphine-induced versus heroin/6-MAM-induced psychomotor activation. This might suggest that the opioid-induced psychomotor stimulation is mediated by different μ-opioid subreceptors than those responsible for their analgesic effects. PMID:24699386

  8. Acetazolamide attenuates chemical-stimulated but not thermal-stimulated acute pain in mice

    PubMed Central

    Sun, Ya-jie; Chen, Ying; Pang, Chong; Wu, Ning; Li, Jin

    2014-01-01

    Aim: Acetazolamide (AZA), a carbonic anhydrase (CA) inhibitor, has been found to alleviate inflammatory and neuropathic pain in rats. In the present study, we investigated the effects of AZA on thermal- and chemical-stimulated acute pain in mice and the possible mechanisms underlying the effects. Methods: Five acute pain models based on thermal and chemical stimuli were established to investigate the effects of AZA on different types of nociception in mice. The antinociceptive effects of methazolamide (another CA inhibitor) and diazepam (a positive allosteric modulator of GABAA receptor) were also examined. The drugs were administered either intraperitoneally (ip) or intrathecally. Results: AZA (50–200 mg/kg, ip) did not produce analgesia in two thermal-stimulated acute pain models, ie, mouse tail-flick and hot-plate tests. In contrast, AZA (50–200 mg/kg, ip) dose-dependently reduced paw licking time in both capsaicin and formalin tests in mice. A similar result was observed in a mouse acetic acid-induced writhing test. However, AZA (10 nmol/mouse, intrathecally) did not produce significant analgesia in the 3 chemical-stimulated acute pain models. In addition, methazolamide (50–200 mg/kg, ip) and diazepam (0.25–1.0 mg/kg, ip) did not produce significant analgesia in either thermal- or chemical-stimulated acute pain. Conclusion: AZA produces analgesia in chemical-stimulated, but not thermal-stimulated acute pain in mice. The attenuation of chemical-stimulated acute pain by AZA may not be due to enhancement of GABAA receptor-mediated inhibition via inhibiting CA activity but rather a peripheral ion channel-related mechanism. PMID:24335844

  9. MDMA (ecstasy) modulates locomotor and prefrontal cortex sensory evoked activity.

    PubMed

    Atkins, Kristal; Burks, Tilithia; Swann, Alan C; Dafny, Nachum

    2009-12-11

    Ingestion of 3, 4-methylenedioxymethamphetamine (MDMA) leads to heightened response to sensory stimulation; thus, MDMA is referred to as "ecstasy" because it produces pleasurable enhancement of such sensation. There have been no electrophysiological studies that report the consequences of MDMA on sensory input. The present study was initiated to study the effects of acute and chronic MDMA on locomotor activity and sensory evoked field potential from freely behaving rats previously implanted with permanent electrodes in the prefrontal cortex (PFC). The main findings of this study are that: (1) acute MDMA augments locomotor behavior and attenuates the incoming sensory input, (2) chronic treatment of MDMA elicits behavioral sensitization, (3) chronic administration of MDMA results in attenuation of the baseline activity of the sensory evoked field potential, and (4) administration of rechallenge MDMA result in enhancement of the PFC sensory evoked field potential. PMID:19769950

  10. Reducing The Cost of Transport and Increasing Walking Distance After Stroke: A Randomized Controlled Trial on Fast Locomotor Training Combined With Functional Electrical Stimulation.

    PubMed

    Awad, Louis N; Reisman, Darcy S; Pohlig, Ryan T; Binder-Macleod, Stuart A

    2016-08-01

    Background Neurorehabilitation efforts have been limited in their ability to restore walking function after stroke. Recent work has demonstrated proof-of-concept for a functional electrical stimulation (FES)-based combination therapy designed to improve poststroke walking by targeting deficits in paretic propulsion. Objectives To determine the effects on the energy cost of walking (EC) and long-distance walking ability of locomotor training that combines fast walking with FES to the paretic ankle musculature (FastFES). Methods Fifty participants >6 months poststroke were randomized to 12 weeks of gait training at self-selected speeds (SS), fast speeds (Fast), or FastFES. Participants' 6-minute walk test (6MWT) distance and EC at comfortable (EC-CWS) and fast (EC-Fast) walking speeds were measured pretraining, posttraining, and at a 3-month follow-up. A reduction in EC-CWS, independent of changes in speed, was the primary outcome. Group differences in the number of 6MWT responders and moderation by baseline speed were also evaluated. Results When compared with SS and Fast, FastFES produced larger reductions in EC (Ps ≤.03). FastFES produced reductions of 24% and 19% in EC-CWS and EC-Fast (Ps <.001), respectively, whereas neither Fast nor SS influenced EC. Between-group 6MWT differences were not observed; however, 73% of FastFES and 68% of Fast participants were responders, in contrast to 35% of SS participants. Conclusions Combining fast locomotor training with FES is an effective approach to reducing the high EC of persons poststroke. Surprisingly, differences in 6MWT gains were not observed between groups. Closer inspection of the 6MWT and EC relationship and elucidation of how reduced EC may influence walking-related disability is warranted. PMID:26621366

  11. The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats.

    PubMed

    Aarde, S M; Huang, P K; Creehan, K M; Dickerson, T J; Taffe, M A

    2013-08-01

    Recreational use of the cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV; "bath salts") has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions. Minimal information exists on the effects of MDPV in laboratory models. This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity. Male Wistar rats were trained to self-administer MDPV or METH (0.05 mg/kg/infusion, i.v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0-5.6 mg/kg s.c.). METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/h; METH Mean = 0.4 and Max = 1.15; MDPV Mean = 0.9 and Max = 5.8). Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0.01-0.50 mg/kg/inf) showed greater potency and efficacy than METH (0.1-0.25 mg/kg/inf). In addition, both MDPV and METH increased locomotor activity at lower doses (0.5-1.0 mg/kg, s.c.) and transiently decreased activity at the highest dose (5.6 mg/kg, s.c.). Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature. Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (∼1.5 mg/kg/h) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased. Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH. PMID:23597511

  12. Escalation of food-maintained responding and sensitivity to the locomotor stimulant effects of cocaine in mice

    PubMed Central

    Goeders, James E.; Murnane, Kevin S.; Banks, Matthew L.; Fantegrossi, William E.

    2009-01-01

    Escalation of drug self-administration is a consequence of extended drug access and is thought to be specifically related to addiction, but few studies have investigated whether intake of non-drug reinforcers may also escalate with extended-access. The goal of these studies was to determine the effects of limited and extended-access to food reinforcers on behavioral and pharmacological endpoints in mice. In distinct groups, responding on a lever was maintained by liquid reinforcement, or nose-poke responses were maintained by sucrose pellets or liquid food in sessions lasting 1 hour (limited-access) or 10 hours (extended-access). The reinforcing strength of each food, as well as reinforcer-associated cues, was tested before and after extended-access using a progressive ratio (PR) schedule, and locomotor activity in response to novelty and increasing doses of cocaine was assessed in an open field setting in all animals after access to food reinforcers. Escalation of lever-pressing behavior reinforced by liquid food, but not nose-poke behavior reinforced by liquid food or sucrose pellets, was observed across successive extended-access sessions. A concomitant increase in the reinforcing strength of liquid food and its associated cues was apparent in mice that escalated their responding, but not in mice that did not escalate. Finally, extended reinforcer access leading to behavioral escalation was accompanied by an increased sensitivity to the psychostimulant effects of cocaine compared to limited-access. These findings indicate that behavioral escalation can develop as a consequence of extended-access to a non-drug reinforcer, although both the nature of the reinforcer (liquid versus solid food) and the topography of the operant response (lever versus nose-poke) modulate its development. These data also suggest that some of the behavioral and pharmacological corrolaries of behavioral escalation observed following extended-access to drug self-administration may not be

  13. Cognitive enhancement by transcranial laser stimulation and acute aerobic exercise.

    PubMed

    Hwang, Jungyun; Castelli, Darla M; Gonzalez-Lima, F

    2016-08-01

    This is the first randomized, controlled study comparing the cognitive effects of transcranial laser stimulation and acute aerobic exercise on the same cognitive tasks. We examined whether transcranial infrared laser stimulation of the prefrontal cortex, acute high-intensity aerobic exercise, or the combination may enhance performance in sustained attention and working memory tasks. Sixty healthy young adults were randomly assigned to one of the following four treatments: (1) low-level laser therapy (LLLT) with infrared laser to two forehead sites while seated (total 8 min, 1064 nm continuous wave, 250 mW/cm(2), 60 J/cm(2) per site of 13.6 cm(2)); (2) acute exercise (EX) of high-intensity (total 20 min, with 10-min treadmill running at 85-90 % VO2max); (3) combined treatment (LLLT + EX); or (4) sham control (CON). Participants were tested for prefrontal measures of sustained attention with the psychomotor vigilance task (PVT) and working memory with the delayed match-to-sample task (DMS) before and after the treatments. As compared to CON, both LLLT and EX reduced reaction time in the PVT [F(1.56) = 4.134, p = 0.01, η (2)  = 0.181] and increased the number of correct responses in the DMS [F(1.56) = 4.690, p = 0.005, η (2)  = 0.201], demonstrating a significant enhancing effect of LLLT and EX on cognitive performance. LLLT + EX effects were similar but showed no significantly greater improvement on PVT and DMS than LLLT or EX alone. The transcranial infrared laser stimulation and acute aerobic exercise treatments were similarly effective for cognitive enhancement, suggesting that they augment prefrontal cognitive functions similarly. PMID:27220529

  14. Spinal neuronal activation during locomotor-like activity enabled by epidural stimulation and 5-HT agonists in spinal rats

    PubMed Central

    Duru, Paul O.; Tillakaratne, Niranjala J.K.; Kim, Jung A.; Zhong, Hui; Stauber, Stacey M.; Pham, Trinh T.; Xiao, Mei S.; Edgerton, V. Reggie; Roy, Roland R.

    2015-01-01

    The neural networks that generate stepping in complete spinal adult rats remain poorly defined. To address this problem we used c-fos (an activity-dependent marker) to identify active interneurons and motoneurons in the lumbar spinal cord of adult spinal rats during a 30-minute bout of bipedal stepping. Spinal rats were either step trained (30 min/day, 3 days/week for 7.5 weeks) or not step-trained. Stepping was enabled by epidural stimulation and the administration of the serotonergic agonists quipazine and 8-OHDPAT. A third group of spinal rats served as untreated (no stimulation, drugs, or stepping) controls. The number of activated cholinergic central canal cluster cells and partition neurons was higher in both step-trained and non-trained than untreated rats, and higher in non-trained than step-trained rats. The latter finding suggests that daily treatment with epidural stimulation plus serotonergic agonist treatment without step training enhanced the excitability of a broader cholinergic interneuronal population than step training. The number of activated interneurons in laminae II-VI of lumbar cross sections was higher in both step-trained and non-trained than untreated rats, and highest in step-trained rats. This finding suggests that this population of interneurons was responsive to epidural stimulation plus serotonergic treatment and that load-bearing induced when stepping had an additive effect. The number of activated motoneurons of all size categories was higher in the step-trained than the other two groups, reflecting a strong effect of loading on motoneuron recruitment. In general, these results indicate that the spinal networks for locomotion are similar with and without brain input. PMID:25789848

  15. The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats

    PubMed Central

    Aarde, S. M.; Huang, P.K.; Creehan, K.M.; Dickerson, T. J.; Taffe, M. A.

    2013-01-01

    Recreational use of the cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV; “bath salts”) has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions. Minimal information exists on the effects of MDPV in laboratory models. This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity. Male Wistar rats were trained to self-administer MDPV or METH (0.05 mg/kg/infusion, i.v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0–5.6 mg/kg s.c.). METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/hour; METH Mean=0.4 and Max = 1.15; MDPV Mean=0.9 and Max = 5.8). Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0.01–0.50 mg/kg/inf) showed greater potency and efficacy than METH (0.1–0.25 mg/kg/inf). In addition, both MDPV and METH increased locomotor activity at lower doses (0.5–1.0 mg/kg, s.c.) and transiently decreased activity at the highest dose (5.6 mg/kg, s.c.). Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature. Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (~1.5 mg/kg/hr) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased. Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH. PMID:23597511

  16. Bovine growth hormone transgenic mice display alterations in locomotor activity and brain monoamine neurochemistry.

    PubMed

    Söderpalm, B; Ericson, M; Bohlooly, M; Engel, J A; Törnell, J

    1999-12-01

    Recent clinical and experimental data indicate a role for GH in mechanisms related to anhedonia/hedonia, psychic energy, and reward. In the present study we have investigated whether bovine GH (bGH) transgenic mice and nontransgenic controls differ in spontaneous locomotor activity, a behavioral response related to brain dopamine (DA) and reward mechanisms, as well as in locomotor activity response to drugs of abuse known to interfere with brain DA systems. The animals were tested for locomotor activity once a week for 4 weeks. When first exposed to the test apparatus, bGH transgenic animals displayed significantly more locomotor activity than controls during the entire registration period (1 h). One week later, after acute pretreatment with saline, the two groups did not differ in locomotor activity, whereas at the third test occasion, bGH mice were significantly more stimulated by d-amphetamine (1 mg/kg, ip) than controls. At the fourth test, a tendency for a larger locomotor stimulatory effect of ethanol (2.5 g/kg, ip) was observed in bGH transgenic mice. bGH mice displayed increased tissue levels of serotonin and 5-hydroxyindoleacetic acid in several brain regions, decreased DA levels in the brain stem, and decreased levels of the DA metabolite 3,4-dihydroxyphenylacetic acid in the mesencephalon and diencephalon, compared with controls. In conclusion, bGH mice display more spontaneous locomotor activity than nontransgenic controls in a novel environment and possibly also a disturbed habituation process. The finding that bGH mice were also more sensitive to d-amphetamine-induced locomotor activity may suggest that the behavioral differences observed are related to differences in brain DA systems, indicating a hyperresponsiveness of these systems in bGH transgenic mice. These findings may constitute a neurochemical basis for the reported psychic effects of GH in humans. PMID:10579325

  17. Effects of consuming a diet high in fat and/or sugar on the locomotor effects of acute and repeated cocaine in male and female C57BL/6J mice

    PubMed Central

    Collins, Gregory T.; Chen, Yu; Tschumi, Chris; Rush, Elise L.; Mensah, Ayele; Koek, Wouter; France, Charles P.

    2015-01-01

    Drug abuse and obesity are serious public health problems. Dopamine plays a central role in mediating the reinforcing effects of drugs and food. Prolonged use of drugs is known to alter the function and/or sensitivity of many neurotransmitter systems, including dopamine, however, the impact of consuming foods high in fat and/or sugar is less clear. These studies characterized the locomotor effects of acute and repeated cocaine in male and female C57BL/6J mice consuming one of four diets: (1) standard chow + water; (2) standard chow + 10% sucrose solution; (3) high-fat chow + water; or (4) high-fat chow + 10% sucrose solution. The acute locomotor effects of cocaine (3.2–32.0 mg/kg) were evaluated four weeks after initiating dietary conditions; the effects of repeated cocaine administration were evaluated after 5, 6, 7, and 12 weeks. During acute tests, mice consuming a diet high in fat and/or sucrose exhibited greater locomotor responses to cocaine than mice consuming standard chow and water, regardless of sex. Although diet-induced enhancements persisted across repeated cocaine testing, locomotor sensitization developed more rapidly in females drinking sucrose (and consuming either standard or high-fat chow) than in females consuming standard chow and water. In addition to providing evidence that consuming a diet high in fat and/or sugar enhances abuse-related effects of cocaine in ways that might increase vulnerability to abuse cocaine, these studies identified a potentially important sex-related difference in the interaction between nutrition and cocaine effects, with the impacts of sucrose consumption being greater in females than in males. PMID:26237320

  18. Acute electrophysiological responses of bradykinin-stimulated human fibroblasts.

    PubMed

    Estacion, M

    1991-05-01

    1. Acute responses to bradykinin in human dermal fibroblasts were studied at 20-24 degrees C using both the patch-clamp technique to monitor ion currents and Fura-2 fluorescence to monitor [Ca2+]i. 2. During subconfluent culture, human dermal fibroblasts can express a diversity of ion channels as described in the preceding paper. 3. When GTP (1 mM) was included in the pipette solution, two additional ion channel populations were transiently augmented in response to bradykinin stimulation. 4. The first is a component of outwardly rectifying current which reached maximal induction within 10-15 s after bradykinin addition (1 microM) and then decayed back to near baseline over 60 s. 5. Ion substitution experiments combined with tail current analysis indicate that the outward current is carried predominantly by K+. 6. Video imaging of single-cell Fura-2 fluorescence from both intact cells and patch-clamped cells showed temporal correlation of the K+ current modulation and the Ca2+ transients in response to bradykinin stimulation. 7. The calcium ionophore, ionomycin, caused both an increase in intracellular calcium and the augmentation of the outward K+ current. The amount of additional K+ current was correlated with [Ca2+]i levels and could be elicited even without the presence of GTP in the pipette. 8. Apamin, a blocker of Ca(2+)-activated K+ channels, inhibited (at 1 microM) the ionomycin-induced modulation of K+ current. 9. In addition, an inward current was transiently induced in response to bradykinin. This current was strictly dependent on the presence of GTP in the pipette solution. This current showed little voltage dependence, as evidenced by a linear current vs. voltage relation, and a reversal potential near but measurably more positive than 0 mV. 10. This current could be decoupled from the Ca2+ transient and be irreversibly induced by including GTP gamma S (100 microM) in the pipette solution. 11. Ion substitution experiments show that this is a non

  19. Extended access of cocaine self-administration results in tolerance to the dopamine-elevating and locomotor-stimulating effects of cocaine.

    PubMed

    Calipari, Erin S; Ferris, Mark J; Jones, Sara R

    2014-01-01

    Tolerance to the neurochemical and psychoactive effects of cocaine after repeated use is a hallmark of cocaine addiction in humans. However, comprehensive studies on tolerance to the behavioral, psychoactive, and neurochemical effects of cocaine following contingent administration in rodents are lacking. We outlined the consequences of extended access cocaine self-administration as it related to tolerance to the psychomotor activating, dopamine (DA) elevating, and DA transporter (DAT) inhibiting effects of cocaine. Cocaine self-administration (1.5 mg/kg/inj; 40 inj; 5 days), which resulted in escalation of first hour intake, caused reductions in evoked DA release and reduced maximal rates of uptake through the DAT as measured by slice voltammetry in the nucleus accumbens core. Furthermore, we report reductions in cocaine-induced uptake inhibition and a corresponding increase in the dose of cocaine required for 50% inhibition of DA uptake (Ki ) at the DAT. Cocaine tolerance at the DAT translated to reductions in cocaine-induced DA overflow as measured by microdialysis. In addition, cocaine-induced elevations in locomotor activity and stereotypy were reduced, while rearing behavior was enhanced in animals with a history of cocaine self-administration. Here, we demonstrate both neurochemical and behavioral cocaine tolerance in an extended-access rodent model of cocaine abuse, which allows for a better understanding of the neurochemical and psychomotor tolerance that develops to cocaine in human addicts. We demonstrate tolerance to the neurochemical and behavioral effects of cocaine following extended-access cocaine self-administration. With respect to neurochemistry, we show reduced cocaine-induced dopamine uptake inhibition, an increased dose of cocaine required for 50% inhibition of the dopamine transporter, and reduced cocaine-induced dopamine overflow. In addition, we show escalation of cocaine intake and reduced cocaine-induced locomotor activity following

  20. Asymmetric control of cycle period by the spinal locomotor rhythm generator in the adult cat.

    PubMed

    Frigon, Alain; Gossard, Jean-Pierre

    2009-10-01

    During walking, a change in speed is accomplished by varying the duration of the stance phase, while the swing phase remains relatively invariant. To determine if this asymmetry in the control of locomotor cycles is an inherent property of the spinal central pattern generator (CPG), we recorded episodes of fictive locomotion in decerebrate cats with or without a complete spinal transection (acute or chronic). During fictive locomotion, stance and swing phases typically correspond to extension and flexion phases, respectively. The extension and flexion phases were determined by measuring the duration of extensor and flexor bursts, respectively. In the vast majority of locomotor episodes, cycle period varied more with the extension phase. This was found without phasic sensory feedback, supraspinal structures, pharmacology or sustained stimulation. We conclude that the control of walking speed is governed by an asymmetry within the organization of the spinal CPG, which can be modified by extraneous factors. PMID:19675066

  1. In vivo potency and efficacy of the novel cathinone α-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone: Self-administration and locomotor stimulation in male rats

    PubMed Central

    Aarde, Shawn M.; Creehan, Kevin M.; Vandewater, Sophia A.; Dickerson, Tobin J.; Taffe, Michael A.

    2015-01-01

    Rationale Numerous substituted cathinone drugs have appeared in recreational use. This variety is often a response to legal actions; the scheduling of 3,4-methylenedioxypyrovalerone (MDPV; “bath salts”) in the U.S.A. was followed by the appearance of the closely related drug α-pyrrolidinopentiophenone (alpha-PVP; “flakka”). Objectives To directly compare the efficacy and potency of alpha-PVP with that of MDPV. Methods Groups of male Wistar rats were trained in the intravenous self-administration (IVSA) alpha-PVP or MDPV under a fixed-ratio 1 schedule of reinforcement. An additional group was examined for locomotor and body temperature responses to non-contingent administration of MDVP or alpha-PVP (1.0, 5.6, 10.0 mg/kg, i.p.). Results Acquisition of alpha-PVP (0.1 mg/kg/infusion) IVSA resulted in low, yet consistent drug intake and excellent discrimination for the drug-paired lever. Dose-substitution (0.05-0.25 mg/kg/infusion) under a fixed-ratio 1 schedule confirmed potency is similar to MDPV in prior studies. In direct comparison to MDPV (0.05 mg/kg/infusion), rats trained on alpha-PVP (0.05 mg/kg/infusion) responded for more infusions but demonstrated similar drug-lever discrimination by the end of acquisition. However, the dose-response (0.018-0.56 mg/kg/inf) functions of these drugs under a progressive-ratio schedule of reinforcement reflected identical efficacy and potency. Peak locomotor responses to MDPV or alpha-PVP were observed after the 1.0 mg/kg, i.p. dose and lasted ~2 hours. Modest body temperature decreases were of similar magnitude (~0.75°C) for each compound. Conclusions The potency and efficacy of MDPV and alpha-PVP were very similar across multiple assays, predicting that the abuse liability of alpha-PVP will be significant and similar to that of MDPV. PMID:25925780

  2. Acute intermittent optogenetic stimulation of nucleus tractus solitarius neurons induces sympathetic long-term facilitation

    PubMed Central

    Yamamoto, Kenta; Lalley, Peter

    2014-01-01

    Acute intermittent hypoxia (AIH) induces sympathetic and phrenic long-term facilitation (LTF), defined as a sustained increase in nerve discharge. We investigated the effects of AIH and acute intermittent optogenetic (AIO) stimulation of neurons labeled with AAV-CaMKIIa, hChR2(H134R), and mCherry in the nucleus of the solitary tract (NTS) of anesthetized, vagotomized, and mechanically ventilated rats. We measured renal sympathetic nerve activity (RSNA), phrenic nerve activity (PNA), power spectral density, and coherence, and we made cross-correlation measurements to determine how AIO stimulation and AIH affected synchronization between PNA and RSNA. Sixty minutes after AIH produced by ventilation with 10% oxygen in balanced nitrogen, RSNA and PNA amplitude increased by 80% and by 130%, respectively (P < 0.01). Sixty minutes after AIO stimulation, RSNA and PNA amplitude increased by 60% and 100%, respectively, (P < 0.01). These results suggest that acute intermittent stimulation of NTS neurons can induce renal sympathetic and phrenic LTF in the absence of hypoxia or chemoreceptor afferent activation. We also found that while acute intermittent optogenetic and hypoxic stimulations increased respiration-related RSNA modulation (P < 0.01), they did not increase synchronization between central respiratory drive and RSNA. We conclude that mechanisms that induce LTF originate within the caudal NTS and extend to other interconnecting neuronal elements of the central nervous cardiorespiratory network. PMID:25519734

  3. Right Median Nerve Electrical Stimulation for Acute Traumatic Coma Patients.

    PubMed

    Lei, Jin; Wang, Lei; Gao, Guoyi; Cooper, Edwin; Jiang, Jiyao

    2015-10-15

    The right median nerve as a peripheral portal to the central nervous system can be electrically stimulated to help coma arousal after traumatic brain injury (TBI). The present study set out to examine the efficacy and safety of right median nerve electrical stimulation (RMNS) in a cohort of 437 comatose patients after severe TBI from August 2005 to December 2011. The patients were enrolled 2 weeks after their injury and assigned to the RMNS group (n=221) receiving electrical stimulation for 2 weeks or the control group (n = 216) treated by standard management according to the date of birth in the month. The baseline data were similar. After the 2-week treatment, the RMNS-treated patients demonstrated a more rapid increase of the mean Glasgow Coma Score, although statistical significance was not reached (8.43 ± 4.98 vs. 7.47 ± 5.37, p = 0.0532). The follow-up data at 6-month post-injury showed a significantly higher proportion of patients who regained consciousness (59.8% vs. 46.2%, p = 0.0073). There was a lower proportion of vegetative persons in the RMNS group than in the control group (17.6% vs. 22.0%, p = 0.0012). For persons regaining consciousness, the functional independence measurement (FIM) score was higher among the RMNS group patients (91.45 ± 8.65 vs. 76.23 ± 11.02, p < 0.001). There were no unique complications associated with the RMNS treatment. The current study, although with some limitations, showed that RMNS may serve as an easy, effective, and noninvasive technique to promote the recovery of traumatic coma in the early phase. PMID:25664378

  4. Acute Stimulant Ingestion and Neurocognitive Performance in Healthy Participants

    PubMed Central

    Powers, Michael E.

    2015-01-01

    Context: Concussion management has become an area of great concern in athletics, and neurocognitive tests, such as Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), are commonly used as management tools. Given the restrictive nature of current management plans, anecdotal concerns have been raised about athletes trying to cheat the assessments and return to participation sooner. Stimulants have been shown to improve neurocognitive measures similar to those used in ImPACT. Therefore, they could possibly improve performance during baseline and postinjury testing. Objective: To examine the effects of a supplement containing stimulants on ImPACT performance. Design: Crossover study. Setting: Research laboratory. Patients or Other Participants: A total of 5 men (age = 20.6 ± 1.5 years, height = 176.3 ± 9.6 cm, mass = 76.9 ± 18.6 kg) and 7 women (age = 20.6 ± 1.1 years, height = 162.9 ± 7.8 cm, mass = 60.9 ± 8.2 kg) with no histories of physician-diagnosed head injury, learning disability, or attention-deficit disorder. Intervention(s): Participants were assessed under supplement (5.5 g of Jacked 3D, which contains caffeine and 1,3-dimethylamylamine), placebo, and control conditions separated by 1 week. Main Outcome Measure(s): I compared ImPACT composite scores for verbal and visual memory, visual motor speed, reaction time, impulse control, and a cognitive-efficiency index under each of the 3 conditions and assessed them 30 minutes after ingestion. Results: I observed a difference when comparing reaction times, as the participants reacted faster during the supplement condition (0.53 ± 0.03 seconds) than during the placebo (0.55 ± 0.03 seconds) and control (0.55 ± 0.03 seconds) conditions (F2,22 = 4.31, P = .03). A difference also was observed for the cognitive-efficiency index, as participants scored higher during the supplement condition (0.49 ± 0.09) than during the placebo (0.41 ± 0.10) and control (0.41 ± 0.12) conditions (F2,22 = 4

  5. Evaluation of focused multipolar stimulation for cochlear implants in acutely deafened cats

    NASA Astrophysics Data System (ADS)

    George, Shefin S.; Wise, Andrew K.; Shivdasani, Mohit N.; Shepherd, Robert K.; Fallon, James B.

    2014-12-01

    Objective. The conductive nature of the fluids and tissues of the cochlea can lead to broad activation of spiral ganglion neurons using contemporary cochlear implant stimulation configurations such as monopolar (MP) stimulation. The relatively poor spatial selectivity is thought to limit implant performance, particularly in noisy environments. Several current focusing techniques have been proposed to reduce the spread of activation with the aim towards achieving improved clinical performance. Approach. The present research evaluated the efficacy of focused multipolar (FMP) stimulation, a relatively new focusing technique in the cochlea, and compared its efficacy to both MP stimulation and tripolar (TP) stimulation. The spread of neural activity across the inferior colliculus (IC), measured by recording the spatial tuning curve, was used as a measure of spatial selectivity. Adult cats (n = 6) were acutely deafened and implanted with an intracochlear electrode array before multi-unit responses were recorded across the cochleotopic gradient of the contralateral IC. Recordings were made in response to acoustic and electrical stimulation using the MP, TP and FMP configurations. Main results. FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation. However, thresholds were significantly higher (p < 0.001) for FMP and TP stimulation compared to MP stimulation. There were no differences found in spatial selectivity and threshold between FMP and TP stimulation. Significance. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance. However, further research will be required to demonstrate the efficacy of these modes of stimulation after longer durations of deafness.

  6. Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

    PubMed Central

    Grumbles, Robert M.; Liu, Yang; Thomas, Christie M.; Wood, Patrick M.

    2013-01-01

    Abstract Few options exist for treatment of pervasive motoneuron death after spinal cord injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis. Local transplantation of embryonic motoneurons into an axotomized peripheral nerve is a promising approach to arrest the atrophy of denervated muscles; however, muscle reinnervation is limited by poor motoneuron survival. The aim of the present study was to test whether acute electrical stimulation of transplanted embryonic neurons promotes motoneuron survival, axon growth, and muscle reinnervation. The sciatic nerve of adult Fischer rats was transected to mimic the widespread denervation seen after disease or injury. Acutely dissociated rat embryonic ventral spinal cord cells were transplanted into the distal tibial nerve stump as a neuron source for muscle reinnervation. Immediately post-transplantation, the cells were stimulated at 20 Hz for 1 h. Other groups were used to control for the cell transplantation and stimulation. When neurons were stimulated acutely, there were significantly more neurons, including cholinergic neurons, 10 weeks after transplantation. This led to enhanced numbers of myelinated axons, reinnervation of more muscle fibers, and more medial and lateral gastrocnemius muscles were functionally connected to the transplant. Reinnervation reduced muscle atrophy significantly. These data support the concept that electrical stimulation rescues transplanted motoneurons and facilitates muscle reinnervation. PMID:23544978

  7. STING Pathway Activation Stimulates Potent Immunity against Acute Myeloid Leukemia.

    PubMed

    Curran, Emily; Chen, Xiufen; Corrales, Leticia; Kline, Douglas E; Dubensky, Thomas W; Duttagupta, Priyanka; Kortylewski, Marcin; Kline, Justin

    2016-06-14

    Type I interferon (IFN), essential for spontaneous T cell priming against solid tumors, is generated through recognition of tumor DNA by STING. Interestingly, we observe that type I IFN is not elicited in animals with disseminated acute myeloid leukemia (AML). Further, survival of leukemia-bearing animals is not diminished in the absence of type I IFN signaling, suggesting that STING may not be triggered by AML. However, the STING agonist, DMXAA, induces expression of IFN-β and other inflammatory cytokines, promotes dendritic cell (DC) maturation, and results in the striking expansion of leukemia-specific T cells. Systemic DMXAA administration significantly extends survival in two AML models. The therapeutic effect of DMXAA is only partially dependent on host type I IFN signaling, suggesting that other cytokines are important. A synthetic cyclic dinucleotide that also activates human STING provided a similar anti-leukemic effect. These data demonstrate that STING is a promising immunotherapeutic target in AML. PMID:27264175

  8. Locomotor exercise in weightlessness

    NASA Technical Reports Server (NTRS)

    Thornton, W.; Whitmore, H.

    1991-01-01

    The requirements for exercise in space by means of locomotion are established and addressed with prototype treadmills for use during long-duration spaceflight. The adaptation of the human body to microgravity is described in terms of 1-G locomotor biomechanics, the effects of reduced activity, and effective activity-replacement techniques. The treadmill is introduced as a complement to other techniques of force replacement with reference given to the angle required for exercise. A motor-driven unit is proposed that can operate at a variety of controlled speeds and equivalent grades. The treadmills permit locomotor exercise as required for long-duration space travel to sustain locomotor and cardiorespiratory capacity at a level consistent with postflight needs.

  9. The 'GALS' locomotor screen.

    PubMed Central

    Doherty, M; Dacre, J; Dieppe, P; Snaith, M

    1992-01-01

    The locomotor system is complex and difficult to examine. A selective clinical process to detect important locomotor abnormalities and functional disability could prove valuable. A screen based on a tested 'minimal' history and examination system is described, together with a simple method of recording. The screen is fast and easy to perform. As well as providing a useful introduction to examination of the locomotor system, the screen includes objective observation of functional movements relevant to activities of daily living. Its inclusion in the undergraduate clerking repertoire could improve junior doctors' awareness and recognition of rheumatic disease and general disability. It could also provide a valuable screening test for use in general practice. Images PMID:1444632

  10. Comparison of treatment effect of neuromuscular electrical stimulation and thermal-tactile stimulation on patients with sub-acute dysphagia caused by stroke

    PubMed Central

    Byeon, Haewon; Koh, Hyeung Woo

    2016-01-01

    [Purpose] The effectiveness of neuromuscular electrical stimulation in the rehabilitation of swallowing remains controversial. This study compared the effectiveness of neuromuscular electrical stimulation and thermal tactile oral stimulation, a traditional swallowing recovery treatment, in patients with sub-acute dysphagia caused by stroke. [Subjects and Methods] Subjects of the present study were 55 patients diagnosed with dysphagia caused by stroke. This study had a nonequivalent control group pretest-posttest design. [Results] Analysis of pre-post values of videofluoroscopic studies of the neuromuscular electrical stimulation and thermal tactile oral stimulation groups using a paired t-test showed no significant difference between the two groups despite both having decreased mean values of the videofluoroscopic studies after treatment. [Conclusion] This study’s findings show that both neuromuscular electrical stimulation and thermal tactile oral stimulation significantly enhanced the swallowing function of patients with sub-acute dysphagia. PMID:27390421

  11. Effects of acute selective pudendal nerve electrical stimulation after simulated childbirth injury

    PubMed Central

    Gill, Bradley C.; Dissaranan, Charuspong; Zutshi, Massarat; Balog, Brian M.; Lin, Danli; Damaser, Margot S.

    2013-01-01

    During childbirth, a combinatorial injury occurs and can result in stress urinary incontinence (SUI). Simulated childbirth injury, consisting of vaginal distension (VD) and pudendal nerve crush (PNC), results in slowed recovery of continence, as well as decreased expression of brain-derived neurotrophic factor (BDNF), a regenerative cytokine. Electrical stimulation has been shown to upregulate BDNF in motor neurons and facilitate axon regrowth through the increase of βII-tubulin expression after injury. In this study, female rats underwent selective pudendal nerve motor branch (PNMB) stimulation after simulated childbirth injury or sham injury to determine whether such stimulation affects bladder and anal function after injury and whether the stimulation increases BDNF expression in Onuf's nucleus after injury. Rats received 4 h of VD followed by bilateral PNC and 1 h of subthreshold electrical stimulation of the left PNMB and sham stimulation of the right PNMB. Rats underwent filling cystometry and anal pressure recording before, during, and after the stimulation. Bladder and anal contractile function were partially disrupted after injury. PNMB stimulation temporarily inhibited bladder contraction after injury. Two days and 1 wk after injury, BDNF expression in Onuf's nucleus of the stimulated side was significantly increased compared with the sham-stimulated side, whereas βII-tubulin expression in Onuf's nucleus of the stimulated side was significantly increased only 1 wk after injury. Acute electrical stimulation of the pudendal nerve proximal to the crush site upregulates BDNF and βII-tubulin in Onuf's nucleus after simulated childbirth injury, which could be a potential preventive option for SUI after childbirth injury. PMID:23152293

  12. Adenylyl cylases 1 and 8 mediate select striatal-dependent behaviors and sensitivity to ethanol stimulation in the adolescent period following acute neonatal ethanol exposure.

    PubMed

    Susick, Laura L; Lowing, Jennifer L; Bosse, Kelly E; Hildebrandt, Clara C; Chrumka, Alexandria C; Conti, Alana C

    2014-08-01

    Neonatal alcohol exposure in rodents causes dramatic neurodegenerative effects throughout the developing nervous system, particularly in the striatum, acutely after exposure. These acute neurodegenerative effects are augmented in mice lacking adenylyl cyclases 1 and 8 (AC1/8) as neonatal mice with a genetic deletion of both AC isoforms (DKO) have increased vulnerability to ethanol-induced striatal neurotoxicity compared to wild type (WT) controls. While neonatal ethanol exposure is known to negatively impact cognitive behaviors, such as executive functioning and working memory in adolescent and adult animals, the threshold of ethanol exposure required to impinge upon developmental behaviors in mice has not been extensively examined. Therefore, the purpose of this study was to determine the behavioral effects of neonatal ethanol exposure using various striatal-dependent developmental benchmarks and to assess the impact of AC1/8 deletion on this developmental progression. WT and DKO mice were treated with 2.5 g/kg ethanol or saline on postnatal day (P)6 and later subjected to the wire suspension, negative geotaxis, postural reflex, grid hang, tail suspension and accelerating rotarod tests at various time points. At P30, mice were evaluated for their hypnotic responses to 4.0 g/kg ethanol by using the loss of righting reflex assay and ethanol-induced stimulation of locomotor activity after 2.0 g/kg ethanol. Ethanol exposure significantly impaired DKO performance in the negative geotaxis test while genetic deletion of AC1/8 alone increased grid hang time and decreased immobility time in the tail suspension test with a concomitant increase in hindlimb clasping behavior. Locomotor stimulation was significantly increased in animals that received ethanol as neonates, peaking significantly in ethanol-treated DKO mice compared to ethanol-treated WT controls, while sedation duration following high-dose ethanol challenge was unaffected. These data indicate that the

  13. Acute Response to Unilateral Unipolar Electrical Carotid Sinus Stimulation in Patients With Resistant Arterial Hypertension.

    PubMed

    Heusser, Karsten; Tank, Jens; Brinkmann, Julia; Menne, Jan; Kaufeld, Jessica; Linnenweber-Held, Silvia; Beige, Joachim; Wilhelmi, Mathias; Diedrich, André; Haller, Hermann; Jordan, Jens

    2016-03-01

    Bilateral bipolar electric carotid sinus stimulation acutely reduced muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in patients with resistant arterial hypertension but is no longer available. The second-generation device uses a smaller unilateral unipolar disk electrode to reduce invasiveness while saving battery life. We hypothesized that the second-generation device acutely lowers BP and MSNA in treatment-resistant hypertensive patients. Eighteen treatment-resistant hypertensive patients (9 women/9 men; 53±11 years; 33±5 kg/m(2)) on stable medications have been included in the study. We monitored finger and brachial BP, heart rate, and MSNA. Without stimulation, BP was 165±31/91±18 mm Hg, heart rate was 75±17 bpm, and MSNA was 48±14 bursts per minute. Acute stimulation with intensities producing side effects that were tolerable in the short term elicited interindividually variable changes in systolic BP (-16.9±15.0 mm Hg; range, 0.0 to -40.8 mm Hg; P=0.002), heart rate (-3.6±3.6 bpm; P=0.004), and MSNA (-2.0±5.8 bursts per minute; P=0.375). Stimulation intensities had to be lowered in 12 patients to avoid side effects at the expense of efficacy (systolic BP, -6.3±7.0 mm Hg; range, 2.8 to -14.5 mm Hg; P=0.028 and heart rate, -1.5±2.3 bpm; P=0.078; comparison against responses with side effects). Reductions in diastolic BP and MSNA (total activity) were correlated (r(2)=0.329; P=0.025). In our patient cohort, unilateral unipolar electric baroreflex stimulation acutely lowered BP. However, side effects may limit efficacy. The approach should be tested in a controlled comparative study. PMID:26831195

  14. Acute Auditory Stimulation with Different Styles of Music Influences Cardiac Autonomic Regulation in Men

    PubMed Central

    da Silva, Sheila Ap. F.; Guida, Heraldo L.; dos Santos Antonio, Ana Marcia; de Abreu, Luiz Carlos; Monteiro, Carlos B. M.; Ferreira, Celso; Ribeiro, Vivian F.; Barnabe, Viviani; Silva, Sidney B.; Fonseca, Fernando L. A.; Adami, Fernando; Petenusso, Marcio; Raimundo, Rodrigo D.; Valenti, Vitor E.

    2014-01-01

    Background: No clear evidence is available in the literature regarding the acute effect of different styles of music on cardiac autonomic control. Objectives: The present study aimed to evaluate the acute effects of classical baroque and heavy metal musical auditory stimulation on Heart Rate Variability (HRV) in healthy men. Patients and Methods: In this study, HRV was analyzed regarding time (SDNN, RMSSD, NN50, and pNN50) and frequency domain (LF, HF, and LF / HF) in 12 healthy men. HRV was recorded at seated rest for 10 minutes. Subsequently, the participants were exposed to classical baroque or heavy metal music for five minutes through an earphone at seated rest. After exposure to the first song, they remained at rest for five minutes and they were again exposed to classical baroque or heavy metal music. The music sequence was random for each individual. Standard statistical methods were used for calculation of means and standard deviations. Besides, ANOVA and Friedman test were used for parametric and non-parametric distributions, respectively. Results: While listening to heavy metal music, SDNN was reduced compared to the baseline (P = 0.023). In addition, the LF index (ms2 and nu) was reduced during exposure to both heavy metal and classical baroque musical auditory stimulation compared to the control condition (P = 0.010 and P = 0.048, respectively). However, the HF index (ms2) was reduced only during auditory stimulation with music heavy metal (P = 0.01). The LF/HF ratio on the other hand decreased during auditory stimulation with classical baroque music (P = 0.019). Conclusions: Acute auditory stimulation with the selected heavy metal musical auditory stimulation decreased the sympathetic and parasympathetic modulation on the heart, while exposure to a selected classical baroque music reduced sympathetic regulation on the heart. PMID:25177673

  15. Acute inflammation stimulates a regenerative response in the neonatal mouse heart

    PubMed Central

    Han, Chunyong; Nie, Yu; Lian, Hong; Liu, Rui; He, Feng; Huang, Huihui; Hu, Shengshou

    2015-01-01

    Cardiac injury in neonatal 1-day-old mice stimulates a regenerative response characterized by reactive cardiomyocyte proliferation, which is distinguished from the fibrotic repair process in adults. Acute inflammation occurs immediately after heart injury and has generally been believed to exert a negative effect on heart regeneration by promoting scar formation in adults; however, little is known about the role of acute inflammation in the cardiac regenerative response in neonatal mice. Here, we show that acute inflammation induced cardiomyocyte proliferation after apical intramyocardial microinjection of immunogenic zymosan A particles into the neonatal mouse heart. We also found that cardiac injury-induced regenerative response was suspended after immunosuppression in neonatal mice, and that cardiomyocytes could not be reactivated to proliferate after neonatal heart injury in the absence of interleukin-6 (IL-6). Furthermore, cardiomyocyte-specific deletion of signal transducer and activator of transcription 3 (STAT3), the major downstream effector of IL-6 signaling, decreased reactive cardiomyocyte proliferation after apical resection. Our results indicate that acute inflammation stimulates the regenerative response in neonatal mouse heart, and suggest that modulation of inflammatory signals might have important implications in cardiac regenerative medicine. PMID:26358185

  16. Aldosterone acutely stimulates NCC activity via a SPAK-mediated pathway

    PubMed Central

    Mistry, Abinash C.; Hanson, Lauren; Mallick, Rickta; Wynne, Brandi M.; Thai, Tiffany L.; Bailey, James L.; Klein, Janet D.; Hoover, Robert S.

    2013-01-01

    Hypertension is a leading cause of morbidity and mortality worldwide, and disordered sodium balance has long been implicated in its pathogenesis. Aldosterone is perhaps the key regulator of sodium balance and thus blood pressure. The sodium chloride cotransporter (NCC) in the distal convoluted tubule of the kidney is a major site of sodium reabsorption and plays a key role in blood pressure regulation. Chronic exposure to aldosterone increases NCC protein expression and function. However, more acute effects of aldosterone on NCC are unknown. In our salt-abundant modern society where chronic salt deprivation is rare, understanding the acute effects of aldosterone is critical. Here, we examined the acute effects (12–36 h) of aldosterone on NCC in the rodent kidney and in a mouse distal convoluted tubule cell line. Studies demonstrated that aldosterone acutely stimulated NCC activity and phosphorylation without affecting total NCC abundance or surface expression. This effect was dependent upon the presence of the mineralocorticoid receptor and serum- and glucocorticoid-regulated kinase 1 (SGK1). Furthermore, STE20/SPS-1-related proline/alanine-rich kinase (SPAK) phosphorylation also increased, and gene silencing of SPAK eliminated the effect of aldosterone on NCC activity. Aldosterone administration via a minipump in adrenalectomized rodents confirmed an increase in NCC phosphorylation without a change in NCC total protein. These data indicate that acute aldosterone-induced SPAK-dependent phosphorylation of NCC increases individual transporter activity. PMID:23739593

  17. Acute ethanol induces apoptosis by stimulating TRPC6 via elevation of superoxide in oxygenated podocytes.

    PubMed

    Lu, Xiao-Yu; Liu, Bing-Chen; Wang, Li-Hua; Yang, Li-Li; Bao, Qing; Zhai, Yu-Jia; Alli, Abdel A; Thai, Tiffany L; Eaton, Douglas C; Wang, Wei-Zhi; Ma, He-Ping

    2015-05-01

    Our recent studies indicate that hydrogen peroxide (H2O2) only at high concentrations can cause oxidative stress in renal epithelial cells and induce apoptosis of podocytes. Consistently, the present study shows that H2O2, even at 1 mM, failed to induce intracellular oxidative stress and apoptosis of the podocytes due to efficient activity of catalase, an enzyme which degrades H2O2 to produce water and oxygen (O2). However, H2O2 acted as a source of O2 to allow acute ethanol to induce superoxide production and cause apoptosis of the podocytes. In contrast, acute ethanol alone did not elevate intracellular superoxide, even though it stimulates expression and translocation of p47phox to the plasma membrane. Inhibition of catalase abolished not only O2 production from H2O2 degradation, but also NOX2-dependent superoxide production in the podocytes challenged by both H2O2 and acute ethanol. In parallel, acute ethanol in the presence of H2O2, but neither ethanol nor H2O2 alone, stimulated transient receptor potential canonical 6 (TRPC6) channels and caused TRPC6-dependent elevation of intracellular Ca2+. These data suggest that exogenous H2O2 does not induce oxidative stress due to rapid degradation to produce O2 in the podocytes, but the oxygenated podocytes become sensitive to acute ethanol challenge and undergo apoptosis via a TRPC6-dependent elevation of intracellular Ca2+. Since cultured podocytes are considered in hypoxic conditions, H2O2 may be used as a source of O2 to establish an ischemia-reperfusion model in some type of cultured cells in which H2O2 does not directly induce intracellular oxidative stress. PMID:25601712

  18. Abdominal Functional Electrical Stimulation to Assist Ventilator Weaning in Acute Tetraplegia: A Cohort Study

    PubMed Central

    McCaughey, Euan J.; Berry, Helen R.; McLean, Alan N.; Allan, David B.; Gollee, Henrik

    2015-01-01

    Background Severe impairment of the major respiratory muscles resulting from tetraplegia reduces respiratory function, causing many people with tetraplegia to require mechanical ventilation during the acute stage of injury. Abdominal Functional Electrical Stimulation (AFES) can improve respiratory function in non-ventilated patients with sub-acute and chronic tetraplegia. The aim of this study was to investigate the clinical feasibility of using an AFES training program to improve respiratory function and assist ventilator weaning in acute tetraplegia. Methods AFES was applied for between 20 and 40 minutes per day, five times per week on four alternate weeks, with 10 acute ventilator dependent tetraplegic participants. Each participant was matched retrospectively with a ventilator dependent tetraplegic control, based on injury level, age and sex. Tidal Volume (VT) and Vital Capacity (VC) were measured weekly, with weaning progress compared to the controls. Results Compliance to training sessions was 96.7%. Stimulated VT was significantly greater than unstimulated VT. VT and VC increased throughout the study, with mean VC increasing significantly (VT: 6.2 mL/kg to 7.8 mL/kg VC: 12.6 mL/kg to 18.7 mL/kg). Intervention participants weaned from mechanical ventilation on average 11 (sd: ± 23) days faster than their matched controls. Conclusion The results of this study indicate that AFES is a clinically feasible technique for acute ventilator dependent tetraplegic patients and that this intervention may improve respiratory function and enable faster weaning from mechanical ventilation. Trial Registration ClinicalTrials.gov NCT02200393 PMID:26047468

  19. Attenuated acute salivary α-amylase responses to gustatory stimulation with citric acid in thin children.

    PubMed

    Chen, Long Hui; Yang, Ze Min; Chen, Wei Wen; Lin, Jing; Zhang, Min; Yang, Xiao Rong; Zhao, Ling Bo

    2015-04-14

    Salivary α-amylase (sAA) is responsible for the 'pre-digestion' of starch in the oral cavity and accounts for up to 50 % of salivary protein in human saliva. An accumulating body of literature suggests that sAA is of nutritional importance; however, it is still not clear how sAA is related to individual's nutritional status. Although copy number variations (CNV) of the salivary amylase gene (AMY1) are associated with variation in sAA levels, a significant amount of sAA variation is not explained by AMY1 CNV. To measure sAA responses to gustatory stimulation with citric acid, we used sAA ratio (the ratio of stimulated sAA levels to those of resting sAA) and investigated acute sAA responses to citric acid in children with normal (Normal-BMI, n 22) and low (Low-BMI, n 21) BMI. The AMY1 gene copy number was determined by quantitative PCR. We, for the first time, demonstrated attenuated acute sAA responses (decreased sAA ratio) to gustatory stimulation in Low-BMI (thinness grade 3) children compared with the Normal-BMI children, which suggest that sAA responses to gustatory stimulation may be of nutritional importance. However, child's nutritional status was not directly related to their resting or stimulated sAA levels, and it was not associated with AMY1 gene copy number. Finally, AMY1 CNV might influence, but did not eventually determine, sAA levels in children. PMID:25784372

  20. Acute inhalation of ozone stimulates bronchial C-fibers and rapidly adapting receptors in dogs

    SciTech Connect

    Coleridge, J.C.G.; Coleridge, H.M.; Schelegle, E.S.; Green, J.F. Univ. of California, San Francisco )

    1993-05-01

    To identify the afferents responsible for initiating the vagally mediated respiratory changes evoked by acute exposure to ozone, the authors recorded vagal impulses in anesthetized, open-chest, artificially ventilated dogs and examined the pulmonary afferent response to ozone (2--3 ppM in air) delivered to the lower trachea for 20--60 min. Bronchial C-fibers (BrCs) were the lung afferents most susceptible to ozone, the activity of 10 of 11 BrCs increasing from 0.2 [+-] 0.2 to 4.6 [+-] 1.3 impulses/s within 1--7 min of ozone exposure. Ten of 15 rapidly adapting receptors (RARs) were stimulated by ozone, their activity increasing from 1.5 [+-] 0.4 to 4.7 [+-] 0.7 impulses/s. Stimulation of RARs (but not of BrCs) appeared secondary to the ozone-induced reduction of lung compliance because it was abolished by hyperinflation of the lungs. Ozone had little effect on pulmonary C-fibers or slowly adapting pulmonary stretch receptors. The authors' results suggest that both BrCs and RARs contribute to the tachypnea and bronchoconstriction evoked by acute exposure to ozone when vagal conduction is intact and that BrCs alone are responsible for the vagally mediated tachypnea that survives vagal cooling to 7[degrees]C. 23 refs., 5 figs.

  1. Transient Muscarinic and Glutamatergic Stimulation of Neural Stem Cells Trigger Acute and Persistent Changes in Differentiation

    PubMed Central

    Samarasinghe, Ranmal A.; Kanuparthi, Prasad S.; Greenamyre, J. Timothy; DeFranco, Donald B.; Di Maio, Roberto

    2014-01-01

    While aberrant cell proliferation and differentiation may contribute to epileptogenesis, the mechanisms linking an initial epileptic insult to subsequent changes in cell fate remain elusive. Using both mouse and human iPSC-derived neural progenitor/stem cells (NPSCs), we found that a combined transient muscarinic and mGluR1 stimulation inhibited overall neurogenesis but enhanced NPSC differentiation into immature GABAergic cells. If treated NPSCs were further passaged, they retained a nearly identical phenotype upon differentiation. A similar profusion of immature GABAergic cells was seen in rats with pilocarpine-induced chronic epilepsy. Furthermore, live cell imaging revealed abnormal de-synchrony of Ca++ transients and altered gap junction intercellular communication following combined muscarinic/glutamatergic stimulation, which was associated with either acute site-specific dephosphorylation of connexin 43 or a long-term enhancement of its degradation. Therefore, epileptogenic stimuli can trigger acute and persistent changes in cell fate by altering distinct mechanisms that function to maintain appropriate intercellular communication between coupled NPSCs. PMID:25003306

  2. Transient muscarinic and glutamatergic stimulation of neural stem cells triggers acute and persistent changes in differentiation.

    PubMed

    Samarasinghe, Ranmal A; Kanuparthi, Prasad S; Timothy Greenamyre, J; DeFranco, Donald B; Di Maio, Roberto

    2014-10-01

    While aberrant cell proliferation and differentiation may contribute to epileptogenesis, the mechanisms linking an initial epileptic insult to subsequent changes in cell fate remain elusive. Using both mouse and human iPSC-derived neural progenitor/stem cells (NPSCs), we found that a combined transient muscarinic and mGluR1 stimulation inhibited overall neurogenesis but enhanced NPSC differentiation into immature GABAergic cells. If treated NPSCs were further passaged, they retained a nearly identical phenotype upon differentiation. A similar profusion of immature GABAergic cells was seen in rats with pilocarpine-induced chronic epilepsy. Furthermore, live cell imaging revealed abnormal de-synchrony of Ca(++) transients and altered gap junction intercellular communication following combined muscarinic/glutamatergic stimulation, which was associated with either acute site-specific dephosphorylation of connexin 43 or a long-term enhancement of its degradation. Therefore, epileptogenic stimuli can trigger acute and persistent changes in cell fate by altering distinct mechanisms that function to maintain appropriate intercellular communication between coupled NPSCs. PMID:25003306

  3. Feeding acutely stimulates fibrinogen synthesis in healthy young and elderly adults.

    PubMed

    Caso, Giuseppe; Mileva, Izolda; Kelly, Patricia; Ahn, Hongshik; Gelato, Marie C; McNurlan, Margaret A

    2009-11-01

    Fibrinogen is a positive acute-phase protein and its hepatic synthesis is enhanced following inflammation and injury. However, it is not clear whether fibrinogen synthesis is also responsive to oral nutrients and whether the response to a meal may be affected by age. Our aim in this study was to investigate the acute effect of oral feeding on fibrinogen synthesis in both young and elderly men and women. Fibrinogen synthesis was determined in 3 separate occasions from the incorporation of l[(2)H(5)]phenylalanine (43 mg/kg body weight) in 8 young (21-35 y) and 8 elderly (>60 y) participants following the ingestion of water (control), a complete liquid meal (15% protein, 30% fat, and 55% carbohydrate), or only the protein component of the meal. The ingestion of the complete meal enhanced fibrinogen fractional synthesis rates (FSR) by 17 +/- 6% in the young and by 38 +/- 10% in the elderly participants compared with the water meal (P < 0.02). A comparable stimulation of FSR occurred with only the protein component of the meal in both young (29 +/- 7%) and elderly participants (41 +/- 9%) compared with the water meal (P < 0.005). Similar results were obtained when fibrinogen synthesis was expressed as absolute synthesis rates (i.e. mg.kg(-1).d(-1)). The results demonstrate that fibrinogen synthesis is acutely stimulated after ingestion of a meal and that this effect can be reproduced by the protein component of the meal alone, both in young and elderly adults. PMID:19759246

  4. Feeding Acutely Stimulates Fibrinogen Synthesis in Healthy Young and Elderly Adults12

    PubMed Central

    Caso, Giuseppe; Mileva, Izolda; Kelly, Patricia; Ahn, Hongshik; Gelato, Marie C.; McNurlan, Margaret A.

    2009-01-01

    Fibrinogen is a positive acute-phase protein and its hepatic synthesis is enhanced following inflammation and injury. However, it is not clear whether fibrinogen synthesis is also responsive to oral nutrients and whether the response to a meal may be affected by age. Our aim in this study was to investigate the acute effect of oral feeding on fibrinogen synthesis in both young and elderly men and women. Fibrinogen synthesis was determined in 3 separate occasions from the incorporation of l[2H5]phenylalanine (43 mg/kg body weight) in 8 young (21–35 y) and 8 elderly (>60 y) participants following the ingestion of water (control), a complete liquid meal (15% protein, 30% fat, and 55% carbohydrate), or only the protein component of the meal. The ingestion of the complete meal enhanced fibrinogen fractional synthesis rates (FSR) by 17 ± 6% in the young and by 38 ± 10% in the elderly participants compared with the water meal (P < 0.02). A comparable stimulation of FSR occurred with only the protein component of the meal in both young (29 ± 7%) and elderly participants (41 ± 9%) compared with the water meal (P < 0.005). Similar results were obtained when fibrinogen synthesis was expressed as absolute synthesis rates (i.e. mg·kg−1·d−1). The results demonstrate that fibrinogen synthesis is acutely stimulated after ingestion of a meal and that this effect can be reproduced by the protein component of the meal alone, both in young and elderly adults. PMID:19759246

  5. Effects of Sodium Butyrate on Methamphetamine-Sensitized Locomotor Activity

    PubMed Central

    Harkness, John H.; Hitzemann, Robert J.; Edmunds, Stephanie; Phillips, Tamara J.

    2012-01-01

    Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge in mice treated repeatedly with MA (10 days of 2 mg/kg MA) or saline (10 days), and then locomotor response to MA challenge was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30 min prior to each MA exposure (10 days of 1 or 2 mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, appeared to increase striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior. PMID:23137698

  6. Acute increase of α-synuclein inhibits synaptic vesicle recycling evoked during intense stimulation

    PubMed Central

    Busch, David J.; Oliphint, Paul A.; Walsh, Rylie B.; Banks, Susan M. L.; Woods, Wendy S.; George, Julia M.; Morgan, Jennifer R.

    2014-01-01

    Parkinson's disease is associated with multiplication of the α-synuclein gene and abnormal accumulation of the protein. In animal models, α-synuclein overexpression broadly impairs synaptic vesicle trafficking. However, the exact steps of the vesicle trafficking pathway affected by excess α-synuclein and the underlying molecular mechanisms remain unknown. Therefore we acutely increased synuclein levels at a vertebrate synapse and performed a detailed ultrastructural analysis of the effects on presynaptic membranes. At stimulated synapses (20 Hz), excess synuclein caused a loss of synaptic vesicles and an expansion of the plasma membrane, indicating an impairment of vesicle recycling. The N-terminal domain (NTD) of synuclein, which folds into an α-helix, was sufficient to reproduce these effects. In contrast, α-synuclein mutants with a disrupted N-terminal α-helix (T6K and A30P) had little effect under identical conditions. Further supporting this model, another α-synuclein mutant (A53T) with a properly folded NTD phenocopied the synaptic vesicle recycling defects observed with wild type. Interestingly, the vesicle recycling defects were not observed when the stimulation frequency was reduced (5 Hz). Thus excess α-synuclein impairs synaptic vesicle recycling evoked during intense stimulation via a mechanism that requires a properly folded N-terminal α-helix. PMID:25273557

  7. Programmed acute electrical stimulation of ventral tegmental area alleviates depressive-like behavior.

    PubMed

    Friedman, Alexander; Frankel, Michael; Flaumenhaft, Yakov; Merenlender, Avia; Pinhasov, Albert; Feder, Yuval; Taler, Michal; Gil-Ad, Irit; Abeles, Moshe; Yadid, Gal

    2009-03-01

    Depressive disorders affect approximately 5% of the population in any given year. Antidepressants may require several weeks to produce their clinical effects. Despite progress being made in this area there is still room and a need to explore additional therapeutic modes to increase treatment effectiveness and responsiveness. Herein, we examined a new method for intervention in depressive states based on deep brain stimulation of the ventral tegmental area (VTA) as a source of incentive motivation and hedonia, in comparison to chemical antidepressants. The pattern of stimulation was fashioned to mimic the firing pattern of VTA neurons in the normal rat. Behavioral manifestations of depression were then monitored weekly using a battery of behavioral tests. The results suggest that treatment with programmed acute electrical stimulation of the VTA substantially alleviates depressive behavior, as compared to chemical antidepressants or electroconvulsive therapy, both in onset time and longitudinal effect. These results were also highly correlated with increases in brain-derived neurotrophic factor mRNA levels in the prefrontal cortex. PMID:18843267

  8. Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study

    PubMed Central

    Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

    2015-01-01

    Objective The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Methods Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Results Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Conclusions Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. Classification of Evidence This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Trial Registration Clinical Trials.gov NCT01815281 PMID:26469868

  9. Muscarinic contribution to the acute cortical effects of vagus nerve stimulation

    NASA Astrophysics Data System (ADS)

    Nichols, Justin A.

    2011-12-01

    Electrical stimulation of the vagus nerve (VNS) has been used to treat more than 60,000 patients with drug-resistant epilepsy and is under investigation as a treatment for several other neurological disorders and conditions. Among these, VNS increases memory performance and enhances recovery of motor and cognitive function in animal models of traumatic brain injury. Recent research indicates that pairing brief VNS with tones multiple-times a day for several weeks induces long-term, input specific cortical plasticity, which can be used to re-normalize the pathological cortical reorganization and eliminate a behavioral correlate of chronic tinnitus in noise exposed rats. Despite the therapeutic potential, the mechanisms of action of VNS remain speculative. In chapter 2 of this dissertation, the acute effects of VNS on cortical synchrony, excitability, and temporal processing are examined. In anesthetized rats implanted with multi-electrode arrays, VNS increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6 to 8 Hz, but not after systemic administration of the muscarinic antagonist scopolamine. Chapter 3 focuses on VNS-tone pairing induced cortical plasticity. Pairing VNS with a tone one hundred times in anesthetized rats resulted in frequency specific plasticity in 31% of the auditory cortex sites. Half of these sites exhibited a frequency specific increase in firing rate and half exhibited a frequency specific decrease. Muscarinic receptor blockade with scopolamine almost entirely prevented the frequency specific increases, but not decreases. Collectively, these experiments demonstrate the capacity for VNS to not only acutely influence cortical synchrony, and excitability, but to also influence temporal and spectral tuning via muscarinic receptor activation. These results strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in the mechanisms of action of VNS and

  10. Blockade of the locomotor stimulant effects of amphetamine by group I, group II, and group III metabotropic glutamate receptor ligands in the rat nucleus accumbens: possible interactions with dopamine receptors.

    PubMed

    David, H N; Abraini, J H

    2003-05-01

    Previous investigations have shown that mGlu receptors would be involved in the amphetamine-induced motor response. However, data are somewhat controversial across studies where methodological protocols vary. The aim of the present study was to determine the involvement of mGlu receptors in the NAcc in the locomotor-activating properties of amphetamine in rats well habituated to their experimental environment, a condition known to modulate the motor response to amphetamine. Focal infusion of the group I mGlu receptor antagonist S-4-CPG, which has no effect on basal motor activity, virtually suppressed the locomotor response to amphetamine, while infusion of the group II mGlu receptor antagonist LY 341495 or the group III mGlu receptor agonist AP4, at the minimal dose that produces locomotor activation, reduced it by approximately a half. These effects were blocked by the group I mGlu receptor agonist DHPG, the group II mGlu receptor agonist APDC, and the group III mGlu receptor antagonist MPPG, respectively. These data confirm that mGlu receptors in the NAcc contribute to the psychostimulant motor effect of amphetamine. Results are discussed from the view of recent neuropharmacological studies that have defined the effects of these mGlu receptor ligands on basal motor activity and DA receptor agonists-induced locomotor responses in rats exposed to similar experimental procedures (Eur J Neuroscience 13 (2001) 2157; Neuropharmacology 41 (2001) 454; Eur J Neuroscience 13 (2001) 869). It is suggested that the contribution of mGlu receptors to the amphetamine-induced motor response may result mainly from their functional, either direct or indirect, interactions with D1-like receptors in the NAcc. PMID:12681370

  11. Carotid baroreceptor stimulation prevents arrhythmias induced by acute myocardial infarction through autonomic modulation.

    PubMed

    Liao, Kai; Yu, Lilei; He, Bo; Huang, Bing; Yang, Kang; Saren, Gaowa; Wang, Songyun; Zhou, Xiaoya; Jiang, Hong

    2014-11-01

    : Electrical carotid baroreceptor stimulation (CBS) has shown therapeutic potential for resistant hypertension and heart failure by resetting autonomic nervous system, but the impacts on arrhythmias remains unclear. This study evaluated the effects of CBS on ventricular electrophysiological properties in normal dog heart and arrhythmias after acute myocardial infarction (AMI). In the acute protocol, anesthetized open chest dogs were exposed to 1 hour left anterior descending coronary occlusion as AMI model. Dogs were received either sham treatment (Control group, n = 8) or CBS (CBS group, n = 8), started 1 hour before AMI. CBS resulted in pronounced prolongation of ventricular effective refractory period and reduction of the maximum action potential duration restitution slope (from 0.85 ± 0.15 in the baseline state to 0.67 ± 0.09 at the end of 1 hour, P < 0.05) before AMI. Number of premature ventricular contractions (277 ± 168 in the Control group vs. 103 ± 84 in the CBS group, P < 0.05) and episodes of ventricular tachycardia/ventricular fibrillation (7 ± 3 in the Control group vs. 3 ± 2 in the CBS group, P < 0.05) was decreased compared with the control group during AMI. CBS buffered low-frequency/high-frequency ratio raise during AMI. Ischemic size was not affected by CBS. CBS may have a beneficial impact on ventricular arrhythmias induced by AMI through modulation of autonomic tone. PMID:24979392

  12. Sex differences in locomotor effects of morphine in the rat

    PubMed Central

    Craft, Rebecca M.; Clark, James L.; Hart, Stephen P.; Pinckney, Megan K.

    2007-01-01

    Sex differences in reinforcing, analgesic and other effects of opioids have been demonstrated; however, the extent to which sex differences in motoric effects of opioids contribute to apparent sex differences in their primary effects is not known. The goal of this study was to compare the effects of the prototypic mu opioid agonist morphine on locomotor activity in male vs. female rats. Saline or morphine (1-10 mg/kg) was administered s.c. to adult Sprague-Dawley rats, which were placed into a photobeam apparatus for 3-5 hr to measure activity. Modulation of morphine's effects by gonadal hormones and by handling (either during the test session or for 4 days before the test session) were examined. Morphine initially suppressed and later increased locomotor activity in both sexes relative to their saline-injected controls, but males were more sensitive than females to the initial locomotor suppressant effect of morphine. Intermittent, brief handling during the 3-hr test session blunted morphine-induced locomotor activation in both sexes. Females in proestrus were the most sensitive to morphine's locomotor-stimulant effect, with females in estrus showing the least response to morphine. Gonadectomized (GDX) males with or without testosterone were equally sensitive to morphine's effects, whereas GDX females treated with estradiol showed a blunted response to morphine's effects, similar to intact females in estrus. Brief handling on each of 4 consecutive days pre-test attenuated morphine's locomotor suppressant effect in males but had no effect in females, thereby eliminating the sex difference. These data suggest that sex differences in morphine's effects on locomotor activity can be attributed to gonadal hormones in females, and to differential stress-induced modulation of morphine's effects in males vs. females. PMID:17217999

  13. The Quantitative Measurement of Reversible Acute Depression after Subthalamic Deep Brain Stimulation in a Patient with Parkinson Disease

    PubMed Central

    Simmons, Daniel B.; Dashtipour, Khashayar

    2015-01-01

    Background. Depression is the most commonly reported mood symptom affecting 2–8% of patients after deep brain stimulation (DBS). Usually, symptoms develop gradually; however there have been cases of reproducible events that the mood symptoms were elicited within seconds to minutes after stimulation and were immediately reversible upon cessation of the stimulus. In the current study, we applied a self-reported questionnaire to assess the patient's mood state. Objective. To objectively measure the reversible acute depression induced by DBS in a patient with Parkinson disease (PD). Methods. A statistically validated Spanish version of the Beck Depression Inventory Short Form (BDI-SF) was used. The questionnaire was administered three times. Results. The patient became acutely depressed within ninety seconds of monopolar stimulation on the right side. His symptoms resolved immediately after changing the setting to bipolar stimulation. The BDI-SF scores during stimulation off, on, and off again were 15, 19, and 6, respectively. Conclusions. The BDI-SF scores increased during stimulation and decreased after cessation. This is consistent with a reversible depressive state. The poststimulation BDI-SF score decreased to less than half of the baseline score. This may suggest that the depression was more severe than the patient was able to express during the stimulation. PMID:26090244

  14. Pituitary and ovarian response to acute stimulation with LH-RH in normal and anovulatory women.

    PubMed

    Aparicio, N J; Casas, P R; Galimberti, D M; de Laborde, N P; Badano, A; García, E P; Meichi, H R; Mirkin, A; Szejner, M; Jaitt, A; Margulies, M; Rosner, J M

    1977-01-01

    The LH FSH estradiol and progesterone responses to acute stimulation with LH-RH were studied in 12 normal women with ovulatory cycles (4 in the initial follicular phase, 4 in the mid-follicular phase and 4 in the late follicular phase) and in two castrated women, two under hormonal contraception, two with ovarian amenorrhea, twelve with central amenorrhea of no detectable origin (6 with normal and 6 with low basal gonadotrophins), eleven anovulatory patients with pseudomenstruation, two with anorexia nervosa, and two with pituitary amenorrhea. Each woman received a rapid i.v. injection of 100 microgram synthetic LH-RH at 9:00 a.m. Serum levels of LH, FSH, estradiol and progesterone were determined by radioimmunoassay in samples collected before and 60, 120, 240 and 480 minutes after injection. The findings were : 1) A significant rise in estradiol and progesterone levels, in addition to LH and FSH elevation, in normal women; 2) A lack of ovarian steroid response in the castrated women and in ovarian amenorrheas, which suggests that the source of steroid response to stimulation is not extragonadal; 3) Significant differences in the responses of the four hormones to LH-RH in the women with central amenorrhea in comparison with the normal group with great variability of results; the steroid response in the presence of a positive LH response might correlate with the severity and/or prognosis of the disorder, a point deserving further study; 4) In anovulatory women with pseudomenstruation, LH responses for the most part normal, and particularly, progesterone responses. PMID:18416

  15. Acute lethal graft-versus-host disease stimulates cellular proliferation in the adult rat liver.

    PubMed

    Klein, R M; Clancy, J; Stuart, S

    1982-11-01

    The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate. PMID:7172201

  16. Combined neuromodulatory interventions in acute experimental pain: assessment of melatonin and non-invasive brain stimulation

    PubMed Central

    da Silva, Nádia Regina Jardim; Laste, Gabriela; Deitos, Alícia; Stefani, Luciana Cadore; Cambraia-Canto, Gustavo; Torres, Iraci L. S.; Brunoni, Andre R.; Fregni, Felipe; Caumo, Wolnei

    2015-01-01

    Transcranial direct current stimulation (tDCS) and melatonin can effectively treat pain. Given their potentially complementary mechanisms of action, their combination could have a synergistic effect. Thus, we tested the hypothesis that compared to the control condition and melatonin alone, tDCS combined with melatonin would have a greater effect on pain modulatory effect, as assessed by quantitative sensory testing (QST) and by the pain level during the Conditioned Pain Modulation (CPM)-task. Furthermore, the combined treatment would have a greater cortical excitability effect as indicated by the transcranial magnetic stimulation (TMS) and on the serum BDNF level. Healthy males (n = 20), (aged 18–40 years), in a blinded, placebo-controlled, crossover, clinical trial, were randomized into three groups: sublingual melatonin (0.25 mg/kg) + a-tDCS, melatonin (0.25 mg/kg) + sham-(s)-tDCS, or sublingual placebo+sham-(s)-tDCS. Anodal stimulation (2 mA, 20 min) was applied over the primary motor cortex. There was a significant difference in the heat pain threshold (°C) for melatonin+a-tDCS vs. placebo+s-tDCS (mean difference: 4.86, 95% confidence interval [CI]: 0.9 to 8.63) and melatonin+s-tDCS vs. placebo+s-tDCS (mean: 5.16, 95% CI: 0.84 to 8.36). There was no difference between melatonin+s-tDCS and melatonin+a-tDCS (mean difference: 0.29, 95% CI: −3.72 to 4.23). The mean change from the baseline on amplitude of motor evocate potential (MEP) was significantly higher in the melatonin+a-tDCS (−19.96% ± 5.2) compared with melatonin+s-tDCS group (−1.36% ± 5.35) and with placebo+s-tDCS group (3.61% ± 10.48), respectively (p < 0.05 for both comparisons). While melatonin alone or combined with a-tDCS did not significantly affect CPM task result, and serum BDNF level. The melatonin effectively reduced pain; however, its association with a-tDCS did not present an additional modulatory effect on acute induced pain. PMID:25873871

  17. Patterned, but not tonic, optogenetic stimulation in motor thalamus improves reaching in acute drug-induced Parkinsonian rats.

    PubMed

    Seeger-Armbruster, Sonja; Bosch-Bouju, Clémentine; Little, Shane T C; Smither, Roseanna A; Hughes, Stephanie M; Hyland, Brian I; Parr-Brownlie, Louise C

    2015-01-21

    High-frequency deep brain stimulation (DBS) in motor thalamus (Mthal) ameliorates tremor but not akinesia in Parkinson's disease. The aim of this study was to investigate whether there are effective methods of Mthal stimulation to treat akinesia. Glutamatergic Mthal neurons, transduced with channelrhodopsin-2 by injection of lentiviral vector (Lenti.CaMKII.hChR2(H134R).mCherry), were selectively stimulated with blue light (473 nm) via a chronically implanted fiber-optic probe. Rats performed a reach-to-grasp task in either acute drug-induced parkinsonian akinesia (0.03-0.07 mg/kg haloperidol, s.c.) or control (vehicle injection) conditions, and the number of reaches was recorded for 5 min before, during, and after stimulation. We compared the effect of DBS using complex physiological patterns previously recorded in the Mthal of a control rat during reaching or exploring behavior, with tonic DBS delivering the same number of stimuli per second (rate-control 6.2 or 1.8 Hz, respectively) and with stimulation patterns commonly used in other brain regions to treat neurological conditions (tonic 130 Hz, theta burst (TBS), and tonic 15 Hz rate-control for TBS). Control rats typically executed >150 reaches per 5 min, which was unaffected by any of the stimulation patterns. Acute parkinsonian rats executed <20 reaches, displaying marked akinesia, which was significantly improved by stimulating with the physiological reaching pattern or TBS (both p < 0.05), whereas the exploring and all tonic patterns failed to improve reaching. Data indicate that the Mthal may be an effective site to treat akinesia, but the pattern of stimulation is critical for improving reaching in parkinsonian rats. PMID:25609635

  18. Childhood Acute Lymphoblastic Leukemia and Indicators of Early Immune Stimulation: A Childhood Leukemia International Consortium Study

    PubMed Central

    Rudant, Jérémie; Lightfoot, Tracy; Urayama, Kevin Y.; Petridou, Eleni; Dockerty, John D.; Magnani, Corrado; Milne, Elizabeth; Spector, Logan G.; Ashton, Lesley J.; Dessypris, Nikolaos; Kang, Alice Y.; Miller, Margaret; Rondelli, Roberto; Simpson, Jill; Stiakaki, Eftichia; Orsi, Laurent; Roman, Eve; Metayer, Catherine; Infante-Rivard, Claire; Clavel, Jacqueline

    2015-01-01

    The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980–2010). The sample included 7,399 ALL cases and 11,181 controls aged 2–14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL. PMID:25731888

  19. Childhood acute lymphoblastic leukaemia and indicators of early immune stimulation: the Estelle study (SFCE)

    PubMed Central

    Ajrouche, R; Rudant, J; Orsi, L; Petit, A; Baruchel, A; Lambilliotte, A; Gambart, M; Michel, G; Bertrand, Y; Ducassou, S; Gandemer, V; Paillard, C; Saumet, L; Blin, N; Hémon, D; Clavel, J

    2015-01-01

    Background: Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL). Methods: The national registry-based case–control study, ESTELLE, was carried out in France in 2010–2011. Population controls were frequency matched with cases on age and gender. The participation rates were 93% for cases and 86% for controls. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (OR) were estimated using unconditional regression models adjusted for age, gender, and potential confounders. Results: In all, 617 ALL and 1225 controls aged ⩾1 year were included. Inverse associations between ALL and early common infections (OR=0.8, 95% confidence interval (CI): 0.6, 1.0), non-first born (⩾3 vs 1; OR=0.7, 95% CI: 0.5, 1.0), attendance of a day-care centre before age 1 year (OR=0.7, 95% CI: 0.5, 1.0), breastfeeding (OR=0.8, 95% CI: 0.7, 1.0), and regular contact with pets (OR=0.8, 95% CI: 0.7, 1.0) in infancy were observed. Conclusions: The results support the hypothesis that conditions promoting the maturation of the immune system in infancy have a protective role with respect to ALL. PMID:25675150

  20. Assessing structural and functional responses of murine hearts to acute and sustained β-adrenergic stimulation in vivo

    PubMed Central

    Puhl, Sarah-Lena; Weeks, Kate L.; Ranieri, Antonella; Avkiran, Metin

    2016-01-01

    Introduction Given the importance of β-adrenoceptor signalling in regulating cardiac structure and function, robust protocols are required to assess potential alterations in such regulation in murine models in vivo. Methods Echocardiography was performed in naïve and stressed (isoprenaline; 30 μg/g/day s.c. for up to 14 days) mice, in the absence or presence of acute β-adrenergic stimulation (dobutamine 0.75 μg/g, i.p.). Controls received saline infusion and/or injection. Hearts were additionally analysed gravimetrically, histologically and biochemically. Results In naïve mice, acute β-adrenoceptor stimulation with dobutamine increased heart rate, left ventricular (LV) fractional shortening (LVFS), ejection fraction (LVEF) and wall thickness and decreased LV diameter (p < 0.05). In stressed mice, dobutamine failed to induce further inotropic and chronotropic responses. Furthermore, following dobutamine injection, these mice exhibited lower LVEF and LVFS at identical heart rates, relative to corresponding controls. Sustained isoprenaline infusion induced LV hypertrophy (increased heart weight, heart weight/body weight ratio, heart weight/tibia length ratio and LV wall thickness (p < 0.05)) by 3 days, with little further change at 14 days. In contrast, increases in LVEF and LVFS were seen only at 14 days (p < 0.05). Discussion We describe protocols for and illustrative data from the assessment of murine cardiac responses to acute and sustained β-adrenergic stimulation in vivo, which would be of value in determining the impact of genetic or pharmacological interventions on such responses. Additionally, our data indicate that acute dobutamine stimulation unmasks early signs of LV dysfunction in the remodelled heart, even at a stage when basal function is enhanced. PMID:26836145

  1. Modulation of locomotor activation by the rostromedial tegmental nucleus.

    PubMed

    Lavezzi, Heather N; Parsley, Kenneth P; Zahm, Daniel S

    2015-02-01

    The rostromedial tegmental nucleus (RMTg) is a strong inhibitor of dopamine neurons in the ventral tegmental area (VTA) reported to influence neurobiological and behavioral responses to reward omission, aversive and fear-eliciting stimuli, and certain drugs of abuse. Insofar as previous studies implicate ventral mesencephalic dopamine neurons as an essential component of locomotor activation, we hypothesized that the RMTg also should modulate locomotion activation. We observed that bilateral infusions into the RMTg of the gamma-aminobutyric acid A (GABAA) agonist, muscimol, indeed activate locomotion. Alternatively, bilateral RMTg infusions of the GABAA receptor antagonist, bicuculline, suppress robust activations of locomotion elicited in two distinct ways: (1) by disinhibitory stimulation of neurons in the lateral preoptic area and (2) by return of rats to an environment previously paired with amphetamine administration. The possibility that suppressive locomotor effects of RMTg bicuculline infusions were due to unintended spread of drug to the nearby VTA was falsified by a control experiment showing that bilateral infusions of bicuculline into the VTA produce activation rather than suppression of locomotion. These results objectively implicate the RMTg in the regulation of locomotor activation. The effect is important because much evidence reported in the literature suggests that locomotor activation can be an involuntary behavioral expression of expectation and/or want without which the willingness to execute adaptive behaviors is impaired. PMID:25164249

  2. Effects of chronic and acute stimulants on brain functional connectivity hubs.

    PubMed

    Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Goldstein, Rita Z

    2015-12-01

    The spatial distribution and strength of information processing 'hubs' are essential features of the brain׳s network topology, and may thus be particularly susceptible to neuropsychiatric disease. Despite growing evidence that drug addiction alters functioning and connectivity of discrete brain regions, little is known about whether chronic drug use is associated with abnormalities in this network-level organization, and if such abnormalities could be targeted for intervention. We used functional connectivity density (FCD) mapping to evaluate how chronic and acute stimulants affect brain hubs (i.e., regions with many short-range or long-range functional connections). Nineteen individuals with cocaine use disorders (CUD) and 15 healthy controls completed resting-state fMRI scans following a randomly assigned dose of methylphenidate (MPH; 20mg) or placebo. Short-range and long-range FCD maps were computed for each participant and medication condition. CUD participants had increased short-range and long-range FCD in the ventromedial prefrontal cortex, posterior cingulate/precuneus, and putamen/amygdala, which in areas of the default mode network correlated with years of use. Across participants, MPH decreased short-range FCD in the thalamus/putamen, and decreased long-range FCD in the supplementary motor area and postcentral gyrus. Increased density of short-range and long-range functional connections to default mode hubs in CUD suggests an overrepresentation of these resource-expensive hubs. While the effects of MPH on FCD were only partly overlapping with those of CUD, MPH-induced reduction in the density of short-range connections to the putamen/thalamus, a network of core relevance to habit formation and addiction, suggests that some FCD abnormalities could be targeted for intervention. PMID:25721787

  3. Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation

    NASA Astrophysics Data System (ADS)

    Nguyen, T. A. K.; DiGiovanna, J.; Cavuscens, S.; Ranieri, M.; Guinand, N.; van de Berg, R.; Carpaneto, J.; Kingma, H.; Guyot, J.-P.; Micera, S.; Perez Fornos, A.

    2016-08-01

    Objective. The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. Approach. Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. Main results. PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. Significance. Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.

  4. Effects of nicotinic acetylcholine receptor agonists in assays of acute pain-stimulated and pain-depressed behaviors in rats.

    PubMed

    Freitas, Kelen C; Carroll, F Ivy; Negus, S Stevens

    2015-11-01

    Agonists at nicotinic acetylcholine receptors (nAChRs) constitute one drug class being evaluated as candidate analgesics. Previous preclinical studies have implicated α4β2 and α7 nAChRs as potential mediators of the antinociceptive effects of (–)-nicotine hydrogen tartrate (nicotine) and other nAChR agonists; however, these studies have relied exclusively on measures of pain-stimulated behavior, which can be defined as behaviors that increase in frequency, rate, or intensity after presentation of a noxious stimulus. Pain is also associated with depression of many behaviors, and drug effects can differ in assays of pain-stimulated versus pain-depressed behavior. Accordingly, this study compared the effects of nicotine, the selective α4/6β2 agonist 5-(123I)iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), and the selective α7 agonist N-(3R)-1-azabicyclo(2.2.2)oct-3-yl-4-chlorobenzamide in assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats. Intraperitoneal injection of dilute lactic acid served as an acute noxious stimulus to either stimulate a stretching response or depress the operant responding, which is maintained by electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. Nicotine produced a dose-dependent, time-dependent, and mecamylamine-reversible blockade of both acid-stimulated stretching and acid-induced depression of ICSS. 5-I-A-85380 also blocked both acid-stimulated stretching and acid-induced depression of ICSS, whereas N-(3R)-1-azabicyclo(2.2.2)oct-3-yl-4-chlorobenzamide produced no effect in either procedure. Both nicotine and 5-I-A-85380 were ≥10-fold more potent in blocking the acid-induced depression of ICSS than in blocking the acid-induced stimulation of stretching. These results suggest that stimulation of α4β2 and/or α6β2 nAChRs may be especially effective to alleviate the signs of pain-related behavioral depression in rats; however, nonselective behavioral effects

  5. Src kinases play a novel dual role in acute pancreatitis affecting severity but no role in stimulated enzyme secretion.

    PubMed

    Nuche-Berenguer, Bernardo; Ramos-Álvarez, Irene; Jensen, R T

    2016-06-01

    In pancreatic acinar cells, the Src family of kinases (SFK) is involved in the activation of several signaling cascades that are implicated in mediating cellular processes (growth, cytoskeletal changes, apoptosis). However, the role of SFKs in various physiological responses such as enzyme secretion or in pathophysiological processes such as acute pancreatitis is either controversial, unknown, or incompletely understood. To address this, in this study, we investigated the role/mechanisms of SFKs in acute pancreatitis and enzyme release. Enzyme secretion was studied in rat dispersed pancreatic acini, in vitro acute-pancreatitis-like changes induced by supramaximal COOH-terminal octapeptide of cholecystokinin (CCK). SFK involvement assessed using the chemical SFK inhibitor (PP2) with its inactive control, 4-amino-7-phenylpyrazol[3,4-d]pyrimidine (PP3), under experimental conditions, markedly inhibiting SFK activation. In CCK-stimulated pancreatic acinar cells, activation occurred of trypsinogen, various MAP kinases (p42/44, JNK), transcription factors (signal transducer and activator of transcription-3, nuclear factor-κB, activator protein-1), caspases (3, 8, and 9) inducing apoptosis, LDH release reflective of necrosis, and various chemokines secreted (monocyte chemotactic protein-1, macrophage inflammatory protein-1α, regulated on activation, normal T cell expressed and secreted). All were inhibited by PP2, not by PP3, except caspase activation leading to apoptosis, which was increased, and trypsin activation, which was unaffected, as was CCK-induced amylase release. These results demonstrate SFK activation is playing a dual role in acute pancreatitis, inhibiting apoptosis and promoting necrosis as well as chemokine/cytokine release inducing inflammation, leading to more severe disease, as well as not affecting secretion. Thus, our studies indicate that SFK is a key mediator of inflammation and pancreatic acinar cell death in acute pancreatitis, suggesting it

  6. Inhibition of Cdk5 in the nucleus accumbens enhances the locomotor-activating and incentive-motivational effects of cocaine.

    PubMed

    Taylor, Jane R; Lynch, Wendy J; Sanchez, Hayde; Olausson, Peter; Nestler, Eric J; Bibb, James A

    2007-03-01

    Neuronal adaptations in striatal dopamine signaling have been implicated in enhanced responses to addictive drugs. Cyclin-dependent kinase 5 (Cdk5) regulates striatal dopamine signaling and is a downstream target gene of the transcription factor DeltaFosB, which accumulates in striatal neurons after chronic cocaine exposure. Here we investigated the role of Cdk5 activity in the nucleus accumbens (NAc) on cocaine-induced locomotor sensitization, responding for reward-associated stimuli (conditioned reinforcement), and cocaine self-administration under a progressive ratio schedule. Repeated infusions of the Cdk5 inhibitor roscovitine into the NAc before cocaine injections augmented both the development and expression of cocaine sensitization without having any intrinsic stimulant actions of its own. Additionally, repeated intra-NAc infusions of roscovitine to saline-injected rats enhanced locomotor responses to a subsequent cocaine challenge. Similar effects were found after infusions of another Cdk5 inhibitor, olomoucine, but not its inactive congener, iso-olomoucine. Repeated inhibition of Cdk5 within the NAc also robustly enhanced the incentive-motivational effects of cocaine, similar to the effect of prior repeated cocaine exposure. The enhanced responding with conditioned reinforcement induced by cocaine persisted at least 2 weeks after the final roscovitine infusion. NAc infusions of olomoucine also produced acute and enduring increases in "breakpoints" achieved on a progressive ratio schedule for cocaine reinforcement. These results demonstrate profound and persistent effects of NAc Cdk5 inhibition on locomotor sensitization and incentive-motivational processes and provide direct evidence for a role for striatal Cdk5-induced alterations in the brain's long-term adaptations to cocaine. PMID:17360491

  7. Acute deep brain stimulation in the thalamic reticular nucleus protects against acute stress and modulates initial events of adult hippocampal neurogenesis.

    PubMed

    Magdaleno-Madrigal, Víctor Manuel; Pantoja-Jiménez, Christopher Rodrigo; Bazaldúa, Adrián; Fernández-Mas, Rodrigo; Almazán-Alvarado, Salvador; Bolaños-Alejos, Fernanda; Ortíz-López, Leonardo; Ramírez-Rodriguez, Gerardo Bernabé

    2016-11-01

    Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression. PMID:27435420

  8. Resting-state fMRI study of acute migraine treatment with kinetic oscillation stimulation in nasal cavity.

    PubMed

    Li, Tie-Qiang; Wang, Yanlu; Hallin, Rolf; Juto, Jan-Erik

    2016-01-01

    Kinetic oscillatory stimulation (KOS) in the nasal cavity is a non-invasive cranial nerve stimulation method with promising efficacy for acute migraine and other inflammatory disorders. For a better understanding of the underlying neurophysiological mechanisms of KOS treatment, we conducted a resting-state functional magnetic resonance imaging (fMRI) study of 10 acute migraine patients and 10 normal control subjects during KOS treatment in a 3 T clinical MRI scanner. The fMRI data were first processed using a group independent component analysis (ICA) method and then further analyzed with a voxel-wise 3-way ANOVA modeling and region of interest (ROI) of functional connectivity metrics. All migraine participants were relieved from their acute migraine symptoms after 10-20 min KOS treatment and remained migraine free for 3-6 months. The resting-state fMRI result indicates that migraine patients have altered intrinsic functional activity in the anterior cingulate, inferior frontal gyrus and middle/superior temporal gyrus. KOS treatment gave rise to up-regulated intrinsic functional activity for migraine patients in a number of brain regions involving the limbic and primary sensory systems, while down regulating temporally the activity for normal controls in a few brain areas, such as the right dorsal posterior insula and inferior frontal gyrus. The result of this study confirms the efficacy of KOS treatment for relieving acute migraine symptoms and reducing attack frequency. Resting-state fMRI measurements demonstrate that migraine is associated with aberrant intrinsic functional activity in the limbic and primary sensory systems. KOS in the nasal cavity gives rise to the adjustment of the intrinsic functional activity in the limbic and primary sensory networks and restores the physiological homeostasis in the autonomic nervous system. PMID:27622142

  9. Creating an acute energy deficit without stimulating compensatory increases in appetite: is there an optimal exercise protocol?

    PubMed

    Deighton, Kevin; Stensel, David J

    2014-05-01

    Recent years have witnessed significant interest from both the scientific community and the media regarding the influence of exercise on subsequent appetite and energy intake responses. This review demonstrates a consensus among the majority of scientific investigations that an acute bout of land-based endurance exercise does not stimulate any compensatory increases in appetite and energy intake on the day of exercise. Alternatively, preliminary evidence suggests that low volume, supramaximal exercise may stimulate an increase in appetite perceptions during the subsequent hours. In accordance with the apparent insensitivity of energy intake to exercise in the short term, the daily energy balance response to exercise appears to be primarily determined by the energy cost of exercise. This finding supports the conclusions of recent training studies that the energy expenditure of exercise is the strongest predictor of fat loss during an exercise programme. PMID:24717417

  10. Electrical stimulation as a treatment intervention to improve function, edema or pain following acute lateral ankle sprains: A systematic review.

    PubMed

    Feger, Mark A; Goetschius, John; Love, Hailey; Saliba, Sue A; Hertel, Jay

    2015-11-01

    The purpose of this systematic review was to assess whether electrical stimulation (ES), when used in conjunction with a standard treatment, can reduce levels of functional impairment, edema, and pain compared to a standard treatment alone, in patients following a lateral ankle sprain. We searched PubMed, CINAHL, SportDiscus, and Medline (OVID) databases through June 2014 using the terms "ankle sprain or ankle sprains or ligament injury or ligamentous injury," and "electric stimulation or electric stimulation or electrotherapy." Our search identified four randomized control trials, of which, neuromuscular ES and high-voltage pulsed stimulation were the only two ES modalities utilized. Effect sizes and 95% confidence intervals (CI) were estimated using Cohen's d for comparison between treatment groups. Three of four effect sizes for function had 95% CI that crossed zero. Twenty-four of the thirty-two effect sizes for edema had 95% CI that crossed zero. All effect sizes for pain had 95% CI that crossed zero. Therefore, the use of ES is not recommended as a means to improve function, reduce edema, or decrease pain in the treatment of acute lateral ankle sprains. PMID:25791198

  11. Protein ingestion acutely inhibits insulin-stimulated muscle carnitine uptake in healthy young men1

    PubMed Central

    Shannon, Chris E; Nixon, Aline V; Greenhaff, Paul L; Stephens, Francis B

    2016-01-01

    Background: Increasing skeletal muscle carnitine content represents an appealing intervention in conditions of perturbed lipid metabolism such as obesity and type 2 diabetes but requires chronic l-carnitine feeding on a daily basis in a high-carbohydrate beverage. Objective: We investigated whether whey protein ingestion could reduce the carbohydrate load required to stimulate insulin-mediated muscle carnitine accretion. Design: Seven healthy men [mean ± SD age: 24 ± 5 y; body mass index (in kg/m2): 23 ± 3] ingested 80 g carbohydrate, 40 g carbohydrate + 40 g protein, or control (flavored water) beverages 60 min after the ingestion of 4.5 g l-carnitine tartrate (3 g l-carnitine; 0.1% 2[H]3-l-carnitine). Serum insulin concentration, net forearm carnitine balance (NCB; arterialized-venous and venous plasma carnitine difference × brachial artery flow), and carnitine disappearance (Rd) and appearance (Ra) rates were determined at 20-min intervals for 180 min. Results: Serum insulin and plasma flow areas under the curve (AUCs) were similarly elevated by carbohydrate [4.5 ± 0.8 U/L · min (P < 0.01) and 0.5 ± 0.6 L (P < 0.05), respectively] and carbohydrate+protein [3.8 ± 0.6 U/L · min (P < 0.01) and 0.4 ± 0.6 L (P = 0.05), respectively] consumption, respectively, compared with the control visit (0.04 ± 0.1 U/L · min and −0.5 ± 0.2 L). Plasma carnitine AUC was greater after carbohydrate+protein consumption (3.5 ± 0.5 mmol/L · min) than after control and carbohydrate visits [2.1 ± 0.2 mmol/L · min (P < 0.05) and 1.9 ± 0.3 mmol/L · min (P < 0.01), respectively]. NCB AUC with carbohydrate (4.1 ± 3.1 μmol) was greater than during control and carbohydrate-protein visits (−8.6 ± 3.0 and −14.6 ± 6.4 μmol, respectively; P < 0.05), as was Rd AUC after carbohydrate (35.7 ± 25.2 μmol) compared with control and carbohydrate consumption [19.7 ± 15.5 μmol (P = 0.07) and 14.8 ± 9.6 μmol (P < 0.05), respectively]. Conclusions: The insulin

  12. [Acute effects of ventricular and bicameral stimulation on plasma levels of natriuretic hormone].

    PubMed

    Lo Bianco, F; Altamura, G; Bianconi, L; Toscano, S; Pandozi, C; Castro, A; Magliocca, V; Gentilucci, G; Magris, B; Santini, M

    1997-10-01

    Atrial natriuretic factor (ANF) is a peptide produced by the atrium in response to increases in atrial pressure. It is a potent vasodilator and recent studies suggest that ANF may modulate vasomotor changes in patients (pts) with pacemaker (PM) syndrome. To evaluate the incidence of pacing mode on peptide secretion, plasma concentrations of ANF were determined in 32 pts (18 men and 14 women, mean age 71 +/- 4 years) with a DDD PM implant. Blood samples were collected one hour after a randomly assigned PM programming either in VVI or DDD mode at 70 ppm. Mean plasma ANF levels were 84.12 +/- 51 pg/ml in DDD mode and 156.0 +/- 15 pg/ml in VVI mode (p < 0.05). In 12 pts presenting ventriculoatrial retroconduction, the ANF levels were 77.16 +/- 50 pg/ml during DDD stimulation and 219.0 +/- 16 pg/ml during VVI stimulation (p < 0.05). ANF level was 88.50 +/- 46 pg/ml in DDD mode and 114.25 +/- 65 pg/ml in VVI mode in the 20 pts without AV retroconduction (p < 0.05). During DDD mode, 18 patients showed a DVI stimulation whereas 14 showed a VDD stimulation: the mean ANF level was 67.40 +/- 15 pg/ml during DVI and 100.40 +/- 28 pg/ml during VDD stimulation; the difference between these data was not significant. The increase in ANF levels during VVI pacing confirms the lower haemodynamic performance of this stimulation mode. The increase of ANF levels during VVI stimulation, which was in the subgroup without AV retroconduction, confirms the benefits of DDD stimulation also in this group of patients as well. Atrial pacing at physiological rates does not trigger the release of ANF. PMID:9410771

  13. Locomotor Expertise Predicts Infants' Perseverative Errors

    ERIC Educational Resources Information Center

    Berger, Sarah E.

    2010-01-01

    This research examined the development of inhibition in a locomotor context. In a within-subjects design, infants received high- and low-demand locomotor A-not-B tasks. In Experiment 1, walking 13-month-old infants followed an indirect path to a goal. In a control condition, infants took a direct route. In Experiment 2, crawling and walking…

  14. A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

    PubMed Central

    Kong, Eric C.; Woo, Katherine; Li, Haiyan; Lebestky, Tim; Mayer, Nasima; Sniffen, Melissa R.; Heberlein, Ulrike; Bainton, Roland J.; Hirsh, Jay; Wolf, Fred W.

    2010-01-01

    Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol. PMID:20376353

  15. Nonreplicating, Cyst-Defective Type II Toxoplasma gondii Vaccine Strains Stimulate Protective Immunity against Acute and Chronic Infection

    PubMed Central

    2015-01-01

    Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II Δku80 Δompdc mutants stimulated a fully protective CD8+ T cell-dependent immunity that prevented acute infection by type I and type II strains of T. gondii, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst-forming Δompdc mutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine. PMID:25776745

  16. Nonreplicating, cyst-defective type II Toxoplasma gondii vaccine strains stimulate protective immunity against acute and chronic infection.

    PubMed

    Fox, Barbara A; Bzik, David J

    2015-05-01

    Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5'-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II Δku80 Δompdc mutants stimulated a fully protective CD8(+) T cell-dependent immunity that prevented acute infection by type I and type II strains of T. gondii, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst-forming Δompdc mutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine. PMID:25776745

  17. Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns

    PubMed Central

    Cruchet, Steeve; Gustafson, Kyle; Benton, Richard; Floreano, Dario

    2015-01-01

    The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs—locomotor bouts—matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior. PMID:26600381

  18. Sigma ligand S14905 and locomotor activity in mice.

    PubMed

    Hascoet, M; Bourin, M; Payeur, R; Lombet, A; Peglion, J L

    1995-12-01

    The binding and locomotor profile of a new sigma ligand, S14905, (isobutyl-N-(1-indan-2yl-piperid-4-yl)N-methyl carbamate, furamate) was studied. The binding data revealed that S14905 has a high affinity for sigma receptors and very low affinity for both dopamine D1 and D2 receptors. We have demonstrated that this sigma ligand prevents the locomotor stimulation induced by morphine (32 and 64 mg/kg), cocaine (16 mg/kg), amphetamine (4 mg/kg) and adrafinil (32 mg/kg) at doses lower than those required to depress spontaneous locomotor activity. The antagonism observed in the present study seems to be more specific of morphine induced hyperlocomotion. The high affinity of this compound for sigma receptors makes it a good choice to study the role of this receptor in the CNS. In addition, S14905 does not directly block dopamine receptors but may modulate them in some manner, and would thus warrant further study as a potential atypical antipsychotic agent, and an antagonist for the hyperactivity induced by opiate drug. PMID:8998401

  19. Acute {beta}-adrenergic stimulation does not alter mitochondrial protein synthesis or markers of mitochondrial biogenesis in adult men.

    PubMed

    Robinson, Matthew M; Richards, Jennifer C; Hickey, Matthew S; Moore, Daniel R; Phillips, Stuart M; Bell, Christopher; Miller, Benjamin F

    2010-01-01

    Exercise-induced expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is dramatically inhibited in mice pretreated with a beta-adrenergic receptor (beta-AR) antagonist, suggesting that beta-ARs play an important role in the regulation of skeletal muscle PGC-1alpha expression, and potentially, mitochondrial biogenesis. Accordingly, we hypothesized that acute beta-AR stimulation would induce transcriptional pathways involved in skeletal muscle mitochondrial biogenesis in humans. Whole body protein turnover (WBPT), myofibrillar protein synthesis (MyPS), skeletal muscle mitochondrial protein synthesis (MiPS), and mitochondrial biogenic signaling were determined in samples of vastus lateralis obtained on two separate occasions in 10 young adult males following 1 h of continuous intravenous administration of saline (CON) or a nonspecific beta-AR agonist [isoproterenol (ISO): 12 ng.kg fat free mass(-1).min(-1)], combined with coinfusion of [1,2](13)C-leucine. beta-AR stimulation induced appreciable increases in heart rate and systolic blood pressure (both P < 0.001) but did not affect mitochondrial biogenic signaling (no change in PGC-1alpha, TFAM, NRF-1, NRF-2, COX, or NADHox expression via RT-PCR; P > 0.05). Additionally, MiPS [CON: 0.099 +/- 0.028, ISO: 0.074 +/- 0.046 (mean +/- SD); P > 0.05] and MyPS (CON: 0.059 +/- 0.008, ISO: 0.055 +/- 0.009; P > 0.05), as well as measures of WBPT were unaffected. On the basis of this investigation, we conclude that acute intravenous beta-AR stimulation does not increase mitochondrial protein synthesis or biogenesis signals in skeletal muscle. PMID:19907002

  20. Hepatic fatty acid biosynthesis is more responsive to protein than carbohydrate in rainbow trout during acute stimulations.

    PubMed

    Dai, Weiwei; Panserat, Stéphane; Kaushik, Sadasivam; Terrier, Frédéric; Plagnes-Juan, Elisabeth; Seiliez, Iban; Skiba-Cassy, Sandrine

    2016-01-01

    The link between dietary carbohydrate/protein and de novo lipogenesis (DNL) remains debatable in carnivorous fish. We aimed to evaluate and compare the response of hepatic lipogenic gene expression to dietary carbohydrate intake/glucose and dietary protein intake/amino acids (AAs) during acute stimulations using both in vivo and in vitro approaches. For the in vivo trial, three different diets and a controlled-feeding method were employed to supply fixed amount of dietary protein or carbohydrate in a single meal; for the in vitro trial, primary hepatocytes were stimulated with a low or high level of glucose (3 mM or 20 mM) and a low or high level of AAs (one-fold or four-fold concentrated AAs). In vitro data showed that a high level of AAs upregulated the expression of enzymes involved in DNL [fatty acid synthase (FAS) and ATP citrate lyase (ACLY)], lipid bioconversion [elongation of very long chain fatty acids like-5 (Elovl5), Elovl2, Δ6 fatty acyl desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD1)], NADPH production [glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme (ME)], and transcriptional factor sterol regulatory element binding protein 1-like, while a high level of glucose only elevated the expression of ME. Data in trout liver also showed that high dietary protein intake induced higher lipogenic gene expression (FAS, ACLY, and Elovl2) regardless of dietary carbohydrate intake, while high carbohydrate intake markedly suppressed the expression of acetyl-CoA carboxylase (ACC) and Elovl5. Overall, we conclude that, unlike rodents or humans, hepatic fatty acid biosynthetic gene expression in rainbow trout is more responsive to dietary protein intake/AAs than dietary carbohydrate intake/glucose during acute stimulations. This discrepancy probably represents one important physiological and metabolic difference between carnivores and omnivores. PMID:26491101

  1. Hindlimb Movement in the Cat Induced by Amplitude-Modulated Stimulation Using Extra-Spinal Electrodes

    PubMed Central

    Tai, Changfeng; Wang, Jicheng; Shen, Bing; Wang, Xianchun; Roppolo, James R.; de Groat, William C.

    2010-01-01

    Hindlimb movement in the cat induced by electrical stimulation with an amplitude-modulated waveform of the dorsal surface of L5-S1 spinal cord or the L5-S1 dorsal/ventral roots was investigated before and after acute spinal cord transection at the T13-L1 level. Stimulation of the spinal cord or dorsal/ventral root at the same spinal segment induced similar movements including coordinated multi-joint flexion or extension. The induced movements changed from flexion to extension when the stimulation was moved from rostral (L5) to caudal (S1) spinal segments. Stimulation of a dorsal or ventral root on one side induced only ipsilateral hindlimb movement. However, stimulation on the dorsal surface of the spinal cord along the midline or across the spinal cord induced bilateral movements. The extension induced by stimulation of L7 dorsal root produced the largest ground reaction force that was strong enough to support body weight. Dorsal root stimulation induced a larger ground reaction force than ventral root stimulation and produced a more graded recruitment curve. Stepping at different speeds could be generated by combined stimulation of the rostral (L5) and the caudal (L6/L7) spinal segments with an appropriate timing between the different stimulation channels. Acute transection of the spinal cord did not change the responses indicating that the induced movements did not require the involvement of the supraspinal locomotor centers. The methods and the stimulation strategy developed in this study might be utilized to restore locomotor function after spinal cord injury. PMID:18369283

  2. Hindlimb movement in the cat induced by amplitude-modulated stimulation using extra-spinal electrodes

    NASA Astrophysics Data System (ADS)

    Tai, Changfeng; Wang, Jicheng; Shen, Bing; Wang, Xianchun; Roppolo, James R.; de Groat, William C.

    2008-06-01

    Hindlimb movement in the cat induced by electrical stimulation with an amplitude-modulated waveform of the dorsal surface of the L5-S1 spinal cord or the L5-S1 dorsal/ventral roots was investigated before and after acute spinal cord transection at the T13-L1 level. Stimulation of the spinal cord or dorsal/ventral root at the same spinal segment induced similar movements including coordinated multi-joint flexion or extension. The induced movements changed from flexion to extension when the stimulation was moved from rostral (L5) to caudal (S1) spinal segments. Stimulation of a dorsal or ventral root on one side induced only ipsilateral hindlimb movement. However, stimulation on the dorsal surface of the spinal cord along the midline or across the spinal cord induced bilateral movements. The extension induced by stimulation of L7 dorsal root produced the largest ground reaction force that was strong enough to support body weight. Dorsal root stimulation induced a larger ground reaction force than ventral root stimulation and produced a more graded recruitment curve. Stepping at different speeds could be generated by combined stimulation of the rostral (L5) and the caudal (L6/L7) spinal segments with an appropriate timing between the different stimulation channels. Acute transection of the spinal cord did not change the responses indicating that the induced movements did not require the involvement of the supraspinal locomotor centers. The methods and the stimulation strategy developed in this study might be utilized to restore locomotor function after spinal cord injury.

  3. Disparate effects of pramipexole on locomotor activity and sensorimotor gating in Sprague-Dawley rats.

    PubMed

    Chang, Wei-li; Breier, Michelle R; Yang, Alex; Swerdlow, Neal R

    2011-10-01

    Prepulse inhibition (PPI) of acoustic startle and locomotor activity are both widely studied in the preclinical development of dopaminergic agents, including those acting at D3 dopamine receptors. In mice, the dopamine D3 receptor-preferential agonist pramipexole (PPX) alters locomotor activity in a biphasic manner at doses that have no effect on PPI. The present study examined the time-course of PPX effects on locomotion and PPI in rats. In adult male Sprague-Dawley rats, PPX (0, 0.1, 0.3, 1.0mg/kg) was injected prior to measurement of locomotor activity for 90 min in photobeam chambers. Based on disparate early vs. late effects of PPX on locomotion, the effects of PPX (0 vs. 0.3mg/kg) on PPI were tested 20 and 80 min after injection. All doses of PPX decreased locomotor activity for 30 min compared to vehicle, and the higher doses stimulated hyperlocomotion later in the session; the late hyperlocomotion, but not the early hypolocomotion, was blocked by the D2-selective antagonist, L741626 (1.0mg/kg sc). In contrast to its locomotor effects, PPX caused a similar reduction in PPI at 20 and 80 min after administration. These findings suggest both a temporal and pharmacological dissociation between PPX effects on locomotor activity and PPI; these two behavioral measures contribute non-redundant information to the investigation of D3-related behavioral pharmacology. PMID:21683731

  4. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    SciTech Connect

    Aburto, Andrés; Barría, Agustín; Cárdenas, Areli; Carpio, Daniel; Figueroa, Carlos D.; Burgos, Maria E.; Ardiles, Leopoldo

    2014-10-15

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity.

  5. Drugs that Target Dopamine Receptors: Changes in Locomotor Activity in Larval Zebrafish

    EPA Science Inventory

    As part of an effort at the US Environmental Protection Agency to develop a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae. This includes assessing the acute effects of drugs known...

  6. TRPA1 receptor stimulation by hydrogen peroxide is critical to trigger hyperalgesia and inflammation in a model of acute gout.

    PubMed

    Trevisan, Gabriela; Hoffmeister, Carin; Rossato, Mateus Fortes; Oliveira, Sara Marchesan; Silva, Mariane Arnoldi; Silva, Cássia Regina; Fusi, Camilla; Tonello, Raquel; Minocci, Daiana; Guerra, Gustavo Petri; Materazzi, Serena; Nassini, Romina; Geppetti, Pierangelo; Ferreira, Juliano

    2014-07-01

    Acute gout attacks produce severe joint pain and inflammation associated with monosodium urate (MSU) crystals leading to oxidative stress production. The transient potential receptor ankyrin 1 (TRPA1) is expressed by a subpopulation of peptidergic nociceptors and, via its activation by endogenous reactive oxygen species, including hydrogen peroxide (H2O2), contributes to pain and neurogenic inflammation. The aim of this study was to investigate the role of TRPA1 in hyperalgesia and inflammation in a model of acute gout attack in rodents. Inflammatory parameters and mechanical hyperalgesia were measured in male Wistar rats and in wild-type (Trpa1(+/+)) or TRPA1-deficient (Trpa1(-/-)) male mice. Animals received intra-articular (ia, ankle) injection of MSU. The role of TRPA1 was assessed by receptor antagonism, gene deletion or expression, sensory fiber defunctionalization, and calcitonin gene-related peptide (CGRP) release. We found that nociceptor defunctionalization, TRPA1 antagonist treatment (via ia or oral administration), and Trpa1 gene ablation abated hyperalgesia and inflammatory responses (edema, H2O2 generation, interleukin-1β release, and neutrophil infiltration) induced by ia MSU injection. In addition, we showed that MSU evoked generation of H2O2 in synovial tissue, which stimulated TRPA1 producing CGRP release and plasma protein extravasation. The MSU-elicited responses were also reduced by the H2O2-detoxifying enzyme catalase and the reducing agent dithiothreitol. TRPA1 activation by MSU challenge-generated H2O2 mediates the entire inflammatory response in an acute gout attack rodent model, thus strengthening the role of the TRPA1 receptor and H2O2 production as potential targets for treatment of acute gout attacks. PMID:24780252

  7. Glutamatergic Mechanisms of Comorbidity Between Acute Stress and Cocaine Self-administration

    PubMed Central

    Garcia-Keller, Constanza; Kupchik, Yonatan; Gipson, Cassandra D; Brown, Robyn M; Spencer, Sade; Bollati, Flavia; Esparza, Maria A; Roberts-Wolfe, Doug; Heinsbroek, Jasper; Bobadilla, Ana-Clara; Cancela, Liliana M; Kalivas, Peter W

    2015-01-01

    There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining if the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate mediated synaptic currents, and dendritic spine morphology. We also determined if acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport, and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders. PMID:26821978

  8. Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration.

    PubMed

    Garcia-Keller, C; Kupchik, Y M; Gipson, C D; Brown, R M; Spencer, S; Bollati, F; Esparza, M A; Roberts-Wolfe, D J; Heinsbroek, J A; Bobadilla, A-C; Cancela, L M; Kalivas, P W

    2016-08-01

    There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders. PMID:26821978

  9. Transcutaneous electrical nerve stimulation (TENS) as compared to placebo TENS for the relief of acute oro-facial pain.

    PubMed

    Hansson, P; Ekblom, A

    1983-02-01

    The present paper describes the effect of high frequency, low frequency and placebo TENS on acute oro-facial pain in 62 patients, attending to an emergency clinic for dental surgery; they had all suffered pain for 1-4 days. The patients were randomly assigned to one of three groups receiving either high frequency (100 Hz), low frequency (2 Hz) or placebo TENS. In the two groups receiving TENS (42 patients) 16 patients reported a reduction in pain intensity exceeding 50%; out of these 16 patients, 4 patients reported complete relief of pain. In the placebo group (20 patients) 2 patients reported a pain reduction of more than 50%; out of these 2 patients, none reported a complete pain relief. Mechanical vibratory stimulation augmented the pain reduction obtained by TENS in 5 out of 10 patients. PMID:6601789

  10. Effect of physical exercise prelabyrinthectomy on locomotor balance compensation in the squirrel monkey

    NASA Technical Reports Server (NTRS)

    Igarashi, M.; Ohashi, K.; Yoshihara, T.; MacDonald, S.

    1989-01-01

    This study examines the effectiveness of physical exercise, during a prepathology state, on locomotor balance compensation after subsequent unilateral labyrinthectomy in squirrel monkeys. An experimental group underwent 3 hr. of daily running exercise on a treadmill for 3 mo. prior to the surgery, whereas a control group was not exercised. Postoperatively, the locomotor balance function of both groups was tested for 3 mo. There was no significant difference in gait deviation counts in the acute phase of compensation. However, in the chronic compensation maintenance phase, the number of gait deviation counts was fewer in the exercise group, which showed significantly better performance stability.

  11. Central noradrenergic mechanisms and the acute stress response during painful stimulation.

    PubMed

    Chapman, C Richard; Bradshaw, David H; Donaldson, Gary W; Jacobson, Robert C; Nakamura, Yoshio

    2014-12-01

    Events that threaten tissue integrity including noxious stimulation activate central noradrenergic circuits, particularly locus coeruleus and its projections. Recent advances in theory hold that an adaptive, defensive shift in brain activity takes place in response to threat. In principle, this shift may accentuate the autonomic and central biomarkers of the perception of painful events and the experience of pain itself. We have examined the effects of an alpha-2 agonist on pupil dilation responses, skin conductance responses, near field somatosensory evoked potentials and pain reports in normal volunteers undergoing repeated trials of painful fingertip stimulation delivered at low, medium and high intensities. In a double-blinded study, 114 healthy male and female volunteers underwent repeated noxious stimulation under baseline, placebo and active drug conditions where the active drug was the alpha-2 agonist tizanidine 4 mg. In contrast to baseline and placebo conditions, tizanidine 4 mg significantly reduced the magnitudes of the mean pupil dilation response, the mean skin conductance response, the mean near field somatosensory evoked potential peak-to-peak amplitude and the mean pain intensity rating. Stimulus intensity significantly altered all three biomarkers and the pain report in a graded fashion. There were no sex differences. These findings support the hypotheses that painful events activate central noradrenergic circuits, and that these circuits play a role in the autonomic and central arousal associated with pain. PMID:25122041

  12. Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats.

    PubMed

    Wiebelhaus, Jason M; Walentiny, D Matthew; Beardsley, Patrick M

    2016-01-01

    Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone's abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose- and time-dependent effects of acute and repeated oxycodone administration in a frequency-rate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and rate-decreasing effects maintained by ICSS similar to μ-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose- and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects. PMID:26491062

  13. Behavioral, neurochemical and molecular changes after acute deep brain stimulation of the infralimbic prefrontal cortex.

    PubMed

    Jiménez-Sánchez, Laura; Linge, Raquel; Campa, Leticia; Valdizán, Elsa M; Pazos, Ángel; Díaz, Álvaro; Adell, Albert

    2016-09-01

    Deep brain stimulation (DBS) is a treatment that has shown some efficacy in treatment-resistant depression. In particular, DBS of the subcallosal cingulate gyrus (Brodmann's area 25, Cg25) has been successfully applied to treat refractory depression. In the rat, we have demonstrated that DBS applied to infralimbic (IL) cortex elevates the levels of glutamate and monoamines in the prefrontal cortex, and requires the stimulation of cortical α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors for its antidepressant-like effects. However, the molecular targets of IL DBS are not fully known. To gain insight into these pathways, we have investigated whether IL DBS is able to reverse the behavioral, biochemical and molecular changes exhibited by the olfactory bulbectomized (OBX) rat. Our results revealed that 1 h IL DBS diminished hyperlocomotion, hyperemotionality and anhedonia, and increased social interaction shown by the OBX rats. Further, IL DBS increased prefrontal efflux of glutamate and serotonin in both sham-operated and OBX rats. With regard to molecular targets, IL DBS increases the synthesis of brain-derived neurotrophic factor (BDNF) and the GluA1 AMPA receptor subunit, and stimulates the Akt/mammalian target of rapamycin (mTOR) as well as the AMPA receptor/c-AMP response element binding (CREB) pathways. Temsirolimus, a known in vivo mTOR blocker, suppressed the antidepressant-like effect of IL DBS in naïve rats in the forced swim test, thus demonstrating for the first time that mTOR signaling is required for the antidepressant-like effects of IL DBS, which is in line with the antidepressant response of other rapid-acting antidepressant drugs. PMID:27108934

  14. Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep.

    PubMed

    Carey, Luke C; Su, Yixin; Valego, Nancy K; Rose, James C

    2006-08-01

    The late-gestation plasma cortisol surge in the sheep fetus is critical for stimulating organ development and parturition. Increased adrenal responsiveness is one of the key reasons for the surge; however, the underlying mechanisms are not fully understood. Our recent studies suggest that ACTH-mediated increased expression of ACTH receptor (ACTH-R) and steroid acute regulatory protein (StAR) may play a role in enhancing responsiveness. Hence, we examined effects of ACTH infusion in fetal sheep on mRNA expression of these two mediators of adrenal responsiveness and assessed the functional consequences of this treatment in vitro. Fetuses of approximately 118 and 138 days of gestational age (dGA) were infused with ACTH-(1-24) for 24 h. Controls received saline infusion. Arterial blood was sampled throughout the infusion. Adrenals were isolated and analyzed for ACTH-R and StAR mRNA, or cells were cultured for 48 h. Cells were stimulated with ACTH, and medium was collected for cortisol measurement. Fetal plasma ACTH and cortisol concentrations increased over the infusion period in both groups. ACTH-R mRNA levels were significantly higher in ACTH-infused fetuses in both the 118 and 138 dGA groups. StAR mRNA increased significantly in both the 118 and 138 dGA groups. Adrenal cells from ACTH-infused fetuses were significantly more responsive to ACTH stimulation in terms of cortisol secretion than those from saline-infused controls. These findings demonstrate that increases in circulating ACTH levels promote increased expression of ACTH-R and StAR mRNA and are coupled to heightened adrenal responsiveness. PMID:16478774

  15. Acute Neuropsychological Effects of Methylphenidate in Stimulant Drug-Naive Boys with ADHD II--Broader Executive and Non-Executive Domains

    ERIC Educational Resources Information Center

    Rhodes, Sinead M.; Coghill, David R.; Matthews, Keith

    2006-01-01

    Background: Accumulating evidence supports methylphenidate-induced enhancement of neuropsychological functioning in attention deficit hyperactivity disorder (ADHD). The present study was designed to investigate the acute effects of the psychostimulant drug, methylphenidate (MPH), on neuropsychological performance in stimulant naive boys with ADHD.…

  16. Acute exercise stimulates macrophage function: possible role of NF-kappaB pathways.

    PubMed

    Silveira, Elza M S; Rodrigues, Mariana F; Krause, Maurício S; Vianna, Damiana R; Almeida, Bibiana S; Rossato, Juliane S; Oliveira, Lino P; Curi, Rui; de Bittencourt, Paulo I Homem

    2007-01-01

    Moderate physical activity when performed on a regular basis presents a number of benefits to the whole organism, especially regarding immune system function, such as augmenting resistance to infections and to cancer growth. Although glutamine production by active muscle cells as well as neuroendocrine alterations mediated by the chronic adaptation to exercise may play a role, the entire mechanism by which exercise makes the immune system aware of challenges remains mostly uncovered. This is particularly true for the effects of an acute exercise session on immune function. In this work, circulating monocytes/macrophages from sedentary rats submitted to an acute (1 h) swimming session were tested for the ability of phagocytosing zymosan particles, phorbol myristate acetate (PMA)-induced hydrogen peroxide production, nitric oxide (NO) release (assessed by nitrate and nitrite production) and the expression of NO synthases (NOS-1, NOS-2 and NOS-3). The results showed that an exercise bout induced a 2.4-fold rise in macrophage phagocytic capacity (p = 0.0041), a 9.6-fold elevation in PMA-induced hydrogen peroxide release into the incubation media (1-h, p = 0.0022) and a 95.5%-augmentation in nitrite basal production (1-h incubation; p = 0.0220), which was associated with a marked expression of NOS-2 (the inducible NOS isoform; p = 0.0319), but not in other NOS gene products. Although NOS-2 expression is nuclear factor-kappaB (NF-kappaB)-dependent, no systemic oxidative stress was found, as inferred from the data of plasma TBARS and glutathione disulphide (GSSG) to glutathione (GSH) ratio in circulating blood erythrocytes which remained constant after the acute exercise. Also, no stressful situation seemed to be faced by monocytes/macrophages, since the expression of the 70-kDa heat shock protein (HSP70) remained unchanged. We conclude that NF-kappaB-dependent induction of NOS-2 and macrophage activation must be related to local factor(s) produced in the surroundings of

  17. Glycyrrhizae Radix Methanol Extract Attenuates Methamphetamine-Induced Locomotor Sensitization and Conditioned Place Preference

    PubMed Central

    Zhao, ZhengLin; Zhang, Jie; Jung, Ji Yun; Chang, Suchan; Zhou, FuBo; Zhao, JunChang; Lee, Bong Hyeo; Yang, Chae Ha; Zhao, RongJie

    2014-01-01

    Glycyrrhizae Radix modulates the neurochemical and locomotor alterations induced by acute psychostimulants in rodents via GABAb receptors. This study investigated the influence of methanol extract from Glycyrrhizae Radix (MEGR) on repeated methamphetamine- (METH-) induced locomotor sensitization and conditioned place preference (CPP). A cohort of rats was treated with METH (1 mg/kg/day) for 6 consecutive days, subjected to 6 days of withdrawal, and then challenged with the same dose of METH to induce locomotor sensitization; during the withdrawal period, the rats were administered MEGR (60 or 180 mg/kg/day). A separate cohort of rats was treated with either METH or saline every other day for 6 days in METH-paired or saline-paired chambers, respectively, to induce CPP. These rats were also administered MEGR (180 mg/kg) prior to every METH or CPP expression test. Pretreatment with MEGR (60 and 180 mg/kg/day) attenuated the expression of METH-induced locomotor sensitization dose-dependently, and 180 mg/kg MEGR significantly inhibited the development and expression of METH-induced CPP. Furthermore, administration of a selective GABAb receptor antagonist (SCH50911) prior to MEGR treatment effectively blocked the inhibitory effects of MEGR on locomotor sensitization, but not CPP. These results suggest that Glycyrrhizae Radix blocked repeated METH-induced behavioral changes via GABAb receptors. PMID:25386216

  18. NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K+

    PubMed Central

    Ruminot, Iván; Gutiérrez, Robin; Peña-Münzenmayer, Gaspar; Añazco, Carolina; Sotelo-Hitschfeld, Tamara; Lerchundi, Rodrigo; Niemeyer, María Isabel; Shull, Gary E.; Barros, L. Felipe

    2011-01-01

    Excitatory synaptic transmission stimulates brain tissue glycolysis. This phenomenon is the signal detected in FDG-PET imaging and, through enhanced lactate production, is also thought to contribute to the fMRI signal. Using a method based on Förster resonance energy transfer in mouse astrocytes, we have recently observed that a small rise in extracellular K+ can stimulate glycolysis by over 300% within seconds. The K+ response was blocked by ouabain, but intracellular engagement of the Na+/K+ ATPase pump with Na+ was ineffective, suggesting that the canonical feedback regulatory pathway involving the Na+ pump and ATP depletion is only permissive and that a second mechanism is involved. Because of their predominant K+ permeability and high expression of the electrogenic Na+/HCO3− cotransporter NBCe1, astrocytes respond to a rise in extracellular K+ with plasma membrane depolarization and intracellular alkalinization. In the present article we show that a fast glycolytic response can be elicited independently of K+ by plasma membrane depolarization or by intracellular alkalinization. The glycolytic response to K+ was absent in astrocytes from NBCe1 null mice (Slc4a4) and was blocked by functional or pharmacological inhibition of the NBCe1. Hippocampal neurons acquired K+-sensitive glycolysis upon heterologous NBCe1 expression. The phenomenon could also be reconstituted in HEK293 cells by co-expression of the NBCe1 and a constitutively-open K+ channel. We conclude that the NBCe1 is a key element in a feedforward mechanism linking excitatory synaptic transmission to fast modulation of glycolysis in astrocytes. PMID:21976511

  19. Levamisole enhances the rewarding and locomotor-activating effects of cocaine in rats

    PubMed Central

    Tallarida, Christopher S.; Tallarida, Ronald J.; Rawls, Scott M.

    2015-01-01

    Background The Drug Enforcement Agency estimates that 80% of cocaine seized in the United States contains the veterinary pharmaceutical levamisole (LVM). One problem with LVM is that it is producing life-threatening neutropenia in an alarming number of cocaine abusers. The neuropharmacological profile of LVM is also suggestive of an agent with modest reinforcing and stimulant effects that could enhance cocaine’s addictive effects. Methods We tested the hypothesis that LVM (ip) enhances the rewarding and locomotor stimulant effects of cocaine (ip) using rat conditioned place preference (CPP) and locomotor assays. Effects of LVM by itself were also tested. Results LVM (0–10 mg/kg) produced CPP at 1 mg/kg (P < 0.05) and locomotor activation at 5 mg/kg (P < 0.05). For CPP combination experiments, a statistically inactive dose of LVM (0.1 mg/kg) was administered with a low dose of cocaine (2.5 mg/kg). Neither agent produced CPP compared to saline (P > 0.05); however, the combination of LVM and cocaine produced enhanced CPP compared to saline or either drug by itself (P < 0.01). For locomotor experiments, the same inactive dose of LVM (0.1 mg/kg, ip) was administered with low (10 mg/kg) and high doses (30 mg/kg) of cocaine. LVM (0.1 mg/kg) enhanced locomotor activation produced by 10 mg/kg of cocaine (P < 0.05) but not by 30 mg/kg (P > 0.05). Conclusions LVM can enhance rewarding and locomotor-activating effects of low doses of cocaine in rats while possessing modest activity of its own. PMID:25683823

  20. Acute stress reduces intraparenchymal lung natural killer cells via beta-adrenergic stimulation

    PubMed Central

    Kanemi, O; Zhang, X; Sakamoto, Y; Ebina, M; Nagatomi, R

    2005-01-01

    There are lines of evidence that natural killer (NK) cells are sensitive to physical and psychological stress. Alterations in the immune system including NK cells are known to differ among tissues and organs. The effect of stress on the lung immune system, however, has not been well documented in spite of the fact that the lungs always confront viral or bacterial attacks as well as tumour cell metastasis. In this study, we intended to investigate the effect of restraint stress on lung lymphocytes including NK cells. C57BL/6 mice were exposed to 2 h restraint stress. The concentration of plasma epinephrine significantly rose immediately after the release from restraint as compared to home-cage control mice. Flow cytometric analysis revealed that the numbers of most lymphocyte subsets including NK cells were decreased in the lungs and blood but not in the spleen, immediately after restraint stress. Immunohistochemical examination revealed that the number of NK cells was decreased in the intraparenchymal region of the lungs, while the number of alveolar macrophages did not change. The decrease in the number of NK cells in the lungs and blood was reversed by the administration of propranolol, a nonselective beta adrenergic antagonist. Taken together, our findings suggest that acute stress reduces the number of intraparenchymal lung NK cells via activation of beta adrenergic receptors. PMID:15606610

  1. Discriminative and locomotor effects of five synthetic cathinones in rats and mice

    PubMed Central

    Gatch, Michael B.; Rutledge, Margaret; Forster, Michael J.

    2014-01-01

    Rationale Synthetic cathinones continue to be sold as “legal” alternatives to methamphetamine or cocaine. As these marginally legal compounds become controlled, suppliers move to other, unregulated compounds. Objectives The purpose of these experiments was to determine whether several temporarily controlled cathinone compounds, which are currently abused on the street, stimulate motor activity and have discriminative stimulus effects similar to cocaine and/or methamphetamine. Methods Methcathinone, pentedrone, pentylone, 3-fluoromethcathinone (3-FMC), and 4-methylethcathinone (4-MEC) were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, i.p.) or methamphetamine (1 mg/kg, i.p.) from saline. Results Methcathinone, pentedrone, and pentylone produced locomotor stimulant effects which lasted up to 6 hours. In addition, pentylone produced convulsions and lethality at 100 mg/kg. 4-MEC produced locomotor stimulant effects which lasted up to 2 hours. Methcathinone, pentedrone, pentylone, 3-FMC, and 4-MEC each produced discriminative stimulus effects similar to those of cocaine and methamphetamine. Conclusions All of the tested compounds produce discriminative stimulus effects similar to either those of cocaine, methamphetamine or both, which suggests that these compounds are likely to have similar abuse liability to cocaine and/or methamphetamine. Pentylone may be more dangerous on the street, as it produced adverse effects at doses that produced maximal stimulant-like effects. PMID:25281225

  2. Deletion of dopamine D1 and D3 receptors differentially affects spontaneous behaviour and cocaine-induced locomotor activity, reward and CREB phosphorylation.

    PubMed

    Karasinska, Joanna M; George, Susan R; Cheng, Regina; O'Dowd, Brian F

    2005-10-01

    Co-localization of dopamine D1 and D3 receptors in striatal neurons suggests that these two receptors interact at a cellular level in mediating dopaminergic function including psychostimulant-induced behaviour. To study D1 and D3 receptor interactions in cocaine-mediated effects, cocaine-induced locomotion and reward in mice lacking either D1, D3 or both receptors were analysed. Spontaneous locomotor activity was increased in D1-/- and D1-/-D3-/- mice and D1-/-D3-/- mice did not exhibit habituation of spontaneous rearing activity. Cocaine (20 mg/kg) increased locomotor activity in wild-type and D3-/- mice, failed to stimulate activity in D1-/- mice and reduced activity in D1-/-D3-/- mice. In the conditioned place preference, all groups exhibited reward at 5, 10 and 20 mg/kg of cocaine. D1-/-D3-/- mice did not demonstrate preference at 2.5 mg/kg of cocaine although preference was observed in wild-type, D1-/- and D3-/- mice. The transcription factor cAMP-responsive element binding protein (CREB) is activated by phosphorylation in striatal regions following dopamine receptor activation. Striatal pCREB levels following acute cocaine were increased in wild-type and D3-/- mice and decreased in D1-/- and D1-/-D3-/- mice. After repeated administration of 2.5 mg/kg of cocaine, D1-/- mice had lower pCREB levels in caudate-putamen and nucleus accumbens. Our findings suggest that, although spontaneous and cocaine-induced horizontal activity depended mainly on the presence of the D1 receptor, there may be crosstalk between D1 and D3 receptors in rearing habituation and the perception of cocaine reward at low doses of the drug. Furthermore, alterations in pCREB levels were associated with changes in cocaine-induced locomotor activity but not reward. PMID:16197514

  3. Effect of granulocyte colony-stimulating factor administration on renal regeneration after experimentally induced acute kidney injury in dogs.

    PubMed

    Lim, Chae-Young; Han, Jae-Ik; Kim, Seung-Gon; Lee, Chang-Min; Park, Hee-Myung

    2016-02-01

    OBJECTIVE To evaluate the effects of granulocyte colony-stimulating factor (GCSF) administration in dogs with experimentally induced acute kidney injury. ANIMALS 6 healthy dogs. PROCEDURES After induction of kidney injury (day 0) with cisplatin (5 mg/kg, IV), the dogs were randomly assigned into 2 groups (n = 3 dogs/group). Then dogs immediately received GCSF (10 μg/kg) or 1 mL of saline (0.9% NaCl) solution (control group) SC; this treatment was repeated once daily for 4 additional days (days 1 through 4). A once-daily CBC (day 0 to 4), serum biochemical analysis (day 0 to 3), and urinalysis (day 0 to 3) were performed for each dog; samples were collected before administration of cisplatin (day 0) and before treatment with GCSF or saline solution (days 1 through 4). After sample collection and treatment on day 4, all dogs were euthanized; kidney tissue samples underwent histologic evaluation, immunohistochemical analyses, and cytokine profiling via reverse transcriptase PCR assay. RESULTS In the GCSF-treated group, the histologic evaluation and immunohistochemical analyses of kidney tissue revealed less fibrotic change and greater proliferation of renal tubular epithelial cells, compared with findings in the control group. The mRNA profiles of kidney tissue from the GCSF-treated group indicated lower expression of tumor necrosis factor-α and tumor growth factor-β, compared with findings in the control group; however, concentrations of factors related to renal regeneration were not greater in the GCSF-treated group. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that GCSF treatment can impede renal fibrosis and increase proliferation of renal tubules after experimentally induced acute kidney injury in dogs. (Am J Vet Res 2016;77:199-207). PMID:27027715

  4. Effects of a 12-hour neuromuscular electrical stimulation treatment program on the recovery of upper extremity function in sub-acute stroke patients: a randomized controlled pilot trial.

    PubMed

    Cui, Bao-Juan; Wang, Dao-Qing; Qiu, Jian-Qing; Huang, Lai-Gang; Zeng, Fan-Shuo; Zhang, Qi; Sun, Min; Liu, Ben-Ling; Sun, Qiang-San

    2015-07-01

    [Purpose] This study investigated the effects of a 12-hour neuromuscular electrical stimulation program in the evening hours on upper extremity function in sub-acute stroke patients. [Subjects and Methods] Forty-five subjects were randomized to one of three groups: 12-hour neuromuscular electrical stimulation group (n=15), which received 12 hours of neuromuscular electrical stimulation and conventional rehabilitation for the affected upper extremity; neuromuscular electrical stimulation group (n=15), which received 30 min of neuromuscular electrical stimulation and conventional rehabilitation; and control group (n=15), which received conventional rehabilitation only. The Fugl-Meyer assessment, Action Research Arm Test, and modified Ashworth scale were used to evaluate the effects before and after intervention, and 4 weeks later. [Results] The improvement in the distal (wrist-hand) components of the Fugl-Meyer assessment and Action Research Arm Test in the 12-hour neuromuscular electrical stimulation group was more significant than that in the neuromuscular electrical stimulation group. No significant difference was found between the two groups in the proximal component (shoulder-elbow) of the Fugl-Meyer assessment. [Conclusion] The 12-hour neuromuscular electrical stimulation group achieved better improvement in upper extremity motor function, especially in the wrist-hand function. This alternative therapeutic approach is easily applicable and can be used in stroke patients during rest or sleep. PMID:26311975

  5. Effect of acute noxious stimulation to the leg or back on muscle synergies during walking.

    PubMed

    van den Hoorn, Wolbert; Hodges, Paul W; van Dieën, Jaap H; Hug, François

    2015-01-01

    This study aimed to examine how acute muscle pain affects muscle coordination during gait with consideration of muscle synergies (i.e., group of muscles activated in synchrony), amplitude of muscle activity and kinematics. A secondary aim was to determine whether any adaptation was specific to pain location. Sixteen participants walked on a treadmill during 5 conditions [control, low back pain (LBP), washout LBP, calf pain (CalfP), and washout CalfP]. Five muscle synergies were identified for all of the conditions. Cross-validation analysis showed that muscle synergy vectors extracted for the control condition accounted for >81% of variance accounted for from the other conditions. Muscle synergies were altered very little in some participants (n = 7 for LBP; n = 10 for CalfP), but were more affected in the others (n = 9 for LBP; n = 6 for CalfP). No systematic differences between pain locations were observed. Considering all participants, synergies related to propulsion and weight acceptance were largely unaffected by pain, whereas synergies related to other functions (trunk control and leg deceleration) were more affected. Gastrocnemii activity was less during both CalfP and LBP than control. Soleus activity was further reduced during CalfP, and this was associated with reduced plantar flexion. Some lower leg muscles exhibited adaptations depending on pain location (e.g., greater vastus lateralis and rectus femoris activity during CalfP than LBP). Overall, these changes in muscle coordination involve a participant-specific strategy that is important to further explore, as it may explain why some people are more likely to develop persistence of a painful condition. PMID:25298391

  6. Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains.

    PubMed

    Wiltshire, T; Ervin, R B; Duan, H; Bogue, M A; Zamboni, W C; Cook, S; Chung, W; Zou, F; Tarantino, L M

    2015-03-01

    Initial sensitivity to psychostimulants can predict subsequent use and abuse in humans. Acute locomotor activation in response to psychostimulants is commonly used as an animal model of initial drug sensitivity and has been shown to have a substantial genetic component. Identifying the specific genetic differences that lead to phenotypic differences in initial drug sensitivity can advance our understanding of the processes that lead to addiction. Phenotyping inbred mouse strain panels are frequently used as a first step for studying the genetic architecture of complex traits. We assessed locomotor activation following a single, acute 20 mg/kg dose of cocaine (COC) in males from 45 inbred mouse strains and observed significant phenotypic variation across strains indicating a substantial genetic component. We also measured levels of COC, the active metabolite, norcocaine and the major inactive metabolite, benzoylecgonine, in plasma and brain in the same set of inbred strains. Pharmacokinetic (PK) and behavioral data were significantly correlated, but at a level that indicates that PK alone does not account for the behavioral differences observed across strains. Phenotypic data from this reference population of inbred strains can be utilized in studies aimed at examining the role of psychostimulant-induced locomotor activation on drug reward and reinforcement and to test theories about addiction processes. Moreover, these data serve as a starting point for identifying genes that alter sensitivity to the locomotor stimulatory effects of COC. PMID:25727211

  7. Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains

    PubMed Central

    Wiltshire, T.; Ervin, R. B.; Duan, H.; Bogue, M. A.; Zamboni, W. C.; Cook, S.; Chung, W.; Zou, F.; Tarantino, L. M.

    2015-01-01

    Initial sensitivity to psychostimulants can predict subsequent use and abuse in humans. Acute locomotor activation in response to psychostimulants is commonly used as an animal model of initial drug sensitivity and has been shown to have a substantial genetic component. Identifying the specific genetic differences that lead to phenotypic differences in initial drug sensitivity can advance our understanding of the processes that lead to addiction. Phenotyping inbred mouse strain panels are frequently used as a first step for studying the genetic architecture of complex traits. We assessed locomotor activation following a single, acute 20 mg/kg dose of cocaine (COC) in males from 45 inbred mouse strains and observed significant phenotypic variation across strains indicating a substantial genetic component. We also measured levels of COC, the active metabolite, norcocaine and the major inactive metabolite, benzoylecgonine, in plasma and brain in the same set of inbred strains. Pharmacokinetic (PK) and behavioral data were significantly correlated, but at a level that indicates that PK alone does not account for the behavioral differences observed across strains. Phenotypic data from this reference population of inbred strains can be utilized in studies aimed at examining the role of psychostimulant-induced locomotor activation on drug reward and reinforcement and to test theories about addiction processes. Moreover, these data serve as a starting point for identifying genes that alter sensitivity to the locomotor stimulatory effects of COC. PMID:25727211

  8. Sound Stabilizes Locomotor-Respiratory Coupling and Reduces Energy Cost

    PubMed Central

    Hoffmann, Charles P.; Torregrosa, Gérald; Bardy, Benoît G.

    2012-01-01

    A natural synchronization between locomotor and respiratory systems is known to exist for various species and various forms of locomotion. This Locomotor-Respiratory Coupling (LRC) is fundamental for the energy transfer between the two subsystems during long duration exercise and originates from mechanical and neurological interactions. Different methodologies have been used to compute LRC, giving rise to various and often diverging results in terms of synchronization, (de-)stabilization via information, and associated energy cost. In this article, the theory of nonlinear-coupled oscillators was adopted to characterize LRC, through the model of the sine circle map, and tested it in the context of cycling. Our specific focus was the sound-induced stabilization of LRC and its associated change in energy consumption. In our experimental study, participants were instructed during a cycling exercise to synchronize either their respiration or their pedaling rate with an external auditory stimulus whose rhythm corresponded to their individual preferential breathing or cycling frequencies. Results showed a significant reduction in energy expenditure with auditory stimulation, accompanied by a stabilization of LRC. The sound-induced effect was asymmetrical, with a better stabilizing influence of the metronome on the locomotor system than on the respiratory system. A modification of the respiratory frequency was indeed observed when participants cycled in synchrony with the tone, leading to a transition toward more stable frequency ratios as predicted by the sine circle map. In addition to the classical mechanical and neurological origins of LRC, here we demonstrated using the sine circle map model that information plays an important modulatory role of the synchronization, and has global energetic consequences. PMID:23028849

  9. The acute effects of flotation restricted environmental stimulation technique on recovery from maximal eccentric exercise.

    PubMed

    Morgan, Paul M; Salacinski, Amanda J; Stults-Kolehmainen, Matthew A

    2013-12-01

    Flotation restricted environmental stimulation technique (REST) involves compromising senses of sound, sight, and touch by creating a quiet dark environment. The individual lies supine in a tank of Epsom salt and water heated to roughly skin temperature (34-35° C). This study was performed to determine if a 1-hour flotation REST session would aid in the recovery process after maximal eccentric knee extensions and flexions. Twenty-four untrained male students (23.29 ± 2.1 years, 184.17 ± 6.85 cm, 85.16 ± 11.54 kg) participated in a randomized, repeated measures crossover study. The participants completed 2 exercise and recovery protocols: a 1-hour flotation REST session and a 1-hour seated control (passive recovery). After isometric muscle strength testing, participants were fatigued with eccentric isokinetic muscle contractions (50 repetitions at 60°·s) of the nondominant knee extensors and flexors. Blood lactate, blood glucose, heart rate, OMNI-rating of perceived exertion for resistance exercise (OMNI-RPE), perceived pain, muscle soreness, and isometric strength were collected before exercise, after treatment, and 24 and 48 hours later. A multivariate analysis of covariance found that treatment had a significant main effect on blood lactate, whereas subsequent univariate analyses of variance found statistical significance with the immediate posttreatment blood lactate measures. The results indicate that flotation REST appears to have a significant impact on blood lactate and perceived pain compared with a 1-hour passive recovery session in untrained healthy men. No difference was found between conditions for muscle strength, blood glucose, muscle soreness, heart rate, or OMNI-RPE. Flotation REST may be used for recreational and professional athletes to help reduce blood lactate levels after eccentric exercise. PMID:23478477

  10. Effects of Functional Electric Stimulation Cycle Ergometry Training on Lower Limb Musculature in Acute Sci Individuals

    PubMed Central

    Demchak, Timothy J.; Linderman, Jon K.; Mysiw, W. Jerry; Jackson, Rebecca; Suun, Jihong; Devor, Steven T.

    2005-01-01

    The purpose of this study was to compare three different intervals for a between sets rest period during a common isokinetic knee extension strength-testing protocol of twenty older Brazilian men (66.30 ± 3.92 yrs). The volunteers underwent unilateral knee extension (Biodex System 3) testing to determine their individual isokinetic peak torque at 60, 90, and 120° ·s-1. The contraction speeds and the rest periods between sets (30, 60 and 90 s) were randomly performed in three different days with a minimum rest period of 48 hours. Significant differences between and within sets were analyzed using a One Way Analysis of Variance (ANOVA) with repeated measures. Although, at angular velocity of 60°·s-1 produced a higher peak torque, there were no significant differences in peak torque among any of the rest periods. Likewise, there were no significant differences between mean peak torque among all resting periods (30, 60 and 90s) at angular velocities of 90 and 120°·s-1. The results showed that during a common isokinetic strength testing protocol a between set rest period of at least 30 s is sufficient for recovery before the next test set in older men. Key Points Muscle fiber cross sectional area (CSAf ) decreased 38% following spinal cord injury (SCI). Early intervention with functional electric stimulation cycle ergometry (FES-CE) prevented further loss of CSAf in SCI patients and increased power output. Muscle myosin heavy chain (MHC) and myonuclear density were unaffected by SCI or FES-CE PMID:24453530

  11. Effects of functional electric stimulation cycle ergometry training on lower limb musculature in acute sci individuals.

    PubMed

    Demchak, Timothy J; Linderman, Jon K; Mysiw, W Jerry; Jackson, Rebecca; Suun, Jihong; Devor, Steven T

    2005-09-01

    The purpose of this study was to compare three different intervals for a between sets rest period during a common isokinetic knee extension strength-testing protocol of twenty older Brazilian men (66.30 ± 3.92 yrs). The volunteers underwent unilateral knee extension (Biodex System 3) testing to determine their individual isokinetic peak torque at 60, 90, and 120° ·s-1. The contraction speeds and the rest periods between sets (30, 60 and 90 s) were randomly performed in three different days with a minimum rest period of 48 hours. Significant differences between and within sets were analyzed using a One Way Analysis of Variance (ANOVA) with repeated measures. Although, at angular velocity of 60°·s-1 produced a higher peak torque, there were no significant differences in peak torque among any of the rest periods. Likewise, there were no significant differences between mean peak torque among all resting periods (30, 60 and 90s) at angular velocities of 90 and 120°·s-1. The results showed that during a common isokinetic strength testing protocol a between set rest period of at least 30 s is sufficient for recovery before the next test set in older men. Key PointsMuscle fiber cross sectional area (CSAf ) decreased 38% following spinal cord injury (SCI).Early intervention with functional electric stimulation cycle ergometry (FES-CE) prevented further loss of CSAf in SCI patients and increased power output.Muscle myosin heavy chain (MHC) and myonuclear density were unaffected by SCI or FES-CE. PMID:24453530

  12. Angiogenesis Is Induced and Wound Size Is Reduced by Electrical Stimulation in an Acute Wound Healing Model in Human Skin

    PubMed Central

    Ud-Din, Sara; Sebastian, Anil; Giddings, Pamela; Colthurst, James; Whiteside, Sigrid; Morris, Julie; Nuccitelli, Richard; Pullar, Christine; Baguneid, Mo; Bayat, Ardeshir

    2015-01-01

    Angiogenesis is critical for wound healing. Insufficient angiogenesis can result in impaired wound healing and chronic wound formation. Electrical stimulation (ES) has been shown to enhance angiogenesis. We previously showed that ES enhanced angiogenesis in acute wounds at one time point (day 14). The aim of this study was to further evaluate the role of ES in affecting angiogenesis during the acute phase of cutaneous wound healing over multiple time points. We compared the angiogenic response to wounding in 40 healthy volunteers (divided into two groups and randomised), treated with ES (post-ES) and compared them to secondary intention wound healing (control). Biopsy time points monitored were days 0, 3, 7, 10, 14. Objective non-invasive measures and H&E analysis were performed in addition to immunohistochemistry (IHC) and Western blotting (WB). Wound volume was significantly reduced on D7, 10 and 14 post-ES (p = 0.003, p = 0.002, p<0.001 respectively), surface area was reduced on days 10 (p = 0.001) and 14 (p<0.001) and wound diameter reduced on days 10 (p = 0.009) and 14 (p = 0.002). Blood flow increased significantly post-ES on D10 (p = 0.002) and 14 (p = 0.001). Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase (p<0.05) in VEGF-A expression by ES treatment on days 7, 10 and 14 (39%, 27% and 35% respectively) and PLGF expression on days 3 and 7 (40% on both days), compared to normal healing. Similarly, WB demonstrated an increase (p<0.05) in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% (p>0.05) on day 14 in VEGF-A expression post-ES compared to controls. Furthermore, organisation of granulation tissue was improved on day 14 post-ES. This randomised controlled trial has shown that ES enhanced wound healing by reduced wound dimensions and increased VEGF-A and PLGF expression in acute cutaneous wounds, which further substantiates the role of ES in up

  13. The effects of inhaled isoparaffins on locomotor activity and operant performance in mice.

    PubMed

    Bowen, S E; Balster, R L

    1998-11-01

    Very little is known qualitatively or quantitatively about the acute central nervous system effects of isoparaffin solvents that are widely used in household and commercial applications. Four isoparaffinic hydrocarbon solvent products differing in predominant carbon number and volatility (ISOPAR-C, -E -G, -H) were tested for their acute effects on locomotor activity and operant performance after inhalation exposure in mice. For both measures, concentration-effect curves were obtained for 30-min exposures using a within-subject design. The more volatile products, ISOPAR-C and -E, were as easily vaporized under our conditions as vapors such as toluene and TCE, which have acute effects on human behavior and are abused. ISOPAR-G was slowly volatilized and ISOPAR-H could not be completely volatilized within our 30-min exposures, suggesting that acute human exposures may be less likely and that it may be more difficult to abuse them. ISOPAR-C, -E, and -G produced reversible increases in locomotor activity of mice at 4000 and 6000 ppm while ISOPAR-C and -E produced reversible concentration-dependent decreases in rates of schedule-controlled operant behavior in approximately the same concentration range as they affected locomotor activity. The fact that only locomotor activity increases were observed with these isoparaffins provides evidence that they produce a different pattern of effects than those reported for abused solvents such as toluene and TCE. Further research will be needed to determine if this different pattern of effects on animal behavior between isoparaffins and abused solvents is correlated with a different pattern of acute intoxication and abuse potential in humans. PMID:9768561

  14. Na+ transport across rumen epithelium of hay-fed sheep is acutely stimulated by the peptide IGF-1 in vitro.

    PubMed

    Shen, Zanming; Martens, Holger; Schweigel-Röntgen, Monika

    2012-04-01

    An energy-rich diet leads to enhanced ruminal Na(+) absorption, which is associated with elevated plasma insulin-like growth factor 1 (IGF-1) levels and an increased number of IGF-1 receptors in rumen papillae. This study examined the in vitro effect of IGF-1 on Na(+) transport across the rumen epithelium of hay-fed sheep, in which the IGF-1 concentration in plasma is lower than in concentrate-fed animals. At concentrations ranging from 20 to 100 μg l(-1), serosal LR3-IGF-1, a recombinant analogue of IGF-1, rapidly (within 30 min) stimulated the mucosal-to-serosal Na(+) flux (J(ms)Na) and consequently the net Na(+) flux (J(net)Na). Compared with controls, J(net)Na increased by about 60% (P < 0.05) following the serosal application of LR3-IGF-1 (20 μg l(-1)). The IGF-1-induced increment of J(ms)Na and J(net)Na was inhibited by mucosal amiloride (1 mmol l(-1)). Neither IGF-1 nor amiloride altered tissue conductance or the short-circuit current of the isolated rumen epithelium. These data support the assumption that the stimulating effect of serosally applied IGF-1 on Na(+) transport across the rumen epithelium is mediated by Na(+)-H(+) exchange (NHE). A further study was performed with cultured rumen epithelial cells and a fluorescent probe (BCECF) to estimate the rate of pH(i) recovery after acid loading. The pH(i) of isolated rumen epithelial cells was 6.43 ± 0.15 after butyrate loading and recovered by 0.26 ± 0.02 pH units (15 min)(-1). Application of LR3-IGF-1 (20 μg l(-1)) significantly increased the rate of pH(i) recovery to 0.33 ± 0.02 pH units (15 min)(-1). Amiloride administration reduced the recovery rate in both control and IGF-1-stimulated cells. These results show, for the first time, that an acute effect of IGF-1 on Na(+) absorption across rumen epithelium results from increased NHE activity. Insulin-like growth factor 1 is thus important for the fast functional adaptation of ruminal Na(+) transport via NHE. PMID:22227200

  15. Effects of cocaine on locomotor activity and schedule-controlled behaviors of inbred rat strains.

    PubMed

    Witkin, J M; Goldberg, S R

    1990-10-01

    Effects of cocaine on several behaviors considered to be reflective of psychomotor stimulation were compared in F344/CR1BR and NBR/NIH inbred rat strains. Effects of cocaine on locomotor activity were compared with effects on either bar-press or nose-poke responses maintained under a multiple fixed-interval 3-min, timeout 1-min schedule of food presentation. In locomotor activity experiments, NBR rats were twice as active as F344 rats under baseline conditions and displayed dose-dependent increases in locomotion (5-20 mg/kg). Maximal increases in locomotor activity of F344 rats were only 200% compared to 1000% in NBR rats. In contrast to locomotor activity, no strain differences in the effects of cocaine were observed under the schedules of food delivery. Bar-pressing under the fixed-interval schedule was increased to a maximum of 150% of control in both rat strains. Nose-poke responding under the fixed-interval schedule was not significantly increased, but timeout rates were increased in both strains. These results suggest that NBR and F344 rats do not differ in general sensitivity to stimulant effects of cocaine but exhibit marked differences in responsivity to cocaine that are dependent upon the behavior studied. Further delineation of the behavioral specificity of strain differences in sensitivity to cocaine should help to identify neurobiological substrates underlying unique biologically determined responses to cocaine. PMID:2080195

  16. Utility of ethological analysis to overcome locomotor confounds in elevated maze models of anxiety.

    PubMed

    Weiss, S M; Wadsworth, G; Fletcher, A; Dourish, C T

    1998-01-01

    The elevated plus-maze is a commonly used model to identify putative anxiolytic and anxiogenic drugs. However, the validity of elevated plus-maze and other recently developed variants such as the elevated zero-maze has recently been questioned on the grounds that both the reference anxiolytic drug chlordiazepoxide and the psychostimulant d-amphetamine increase open arm exploration and stimulate locomotor activity. These findings suggest that measures of "anxiety" in the elevated maze cannot be adequately dissociated from simple changes in locomotor activity, which may confound the interpretation of results obtained using these models. A variety of approaches to assess drug effects on locomotor activity in the elevated maze have been suggested, including the use of total and closed arm entries, as well as supplementary tests such as exploration of the holeboard apparatus. However, all these approaches utilise the measurement of exploration in a novel environment, and as such, could potentially be influenced by either changes in anxiety or locomotor activity. Recently, it has been shown that ethological measures of "risk assessment", such as stretched-attend postures and head-dipping, are sensitive indicators of drug-effects in the elevated maze. The present study assessed the utility of ethological analysis in dissociating locomotor activity from "anxiety" by comparing the effects of d-amphetamine to those of chlordiazepoxide in the rat elevated zero-maze. The results showed that both chlordiazepoxide and d-amphetamine increase the amount of time spent in the open arms and reduce "risk assessment" without increasing line crossing or rearing. These results confirm that under certain test conditions, psychostimulants are capable of producing "false-positives" in elevated maze models, and that both traditional methods and the ethological measures used in this study fail to unequivocally dissociate drug effects on anxiety from effects on locomotor activity. Further

  17. Mephedrone interactions with cocaine: prior exposure to ‘bath salt’ constituent enhances cocaine-induced locomotor activation in rats

    PubMed Central

    Gregg, Ryan A.; Tallarida, Christopher S.; Reitz, Allen B.; Rawls, Scott M.

    2014-01-01

    Concurrent use of mephedrone (4-methylmethcathinone) (MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity following pretreatment with cocaine or MEPH than following pretreatment with saline. METH challenge produced greater locomotor activity following METH pretreatment than following saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bi-directional and did not extend to METH, suggesting the phenomenon is sensitive to specific psychostimulants. PMID:24126218

  18. Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats.

    PubMed

    Gregg, Ryan A; Tallarida, Christopher S; Reitz, Allen B; Rawls, Scott M

    2013-12-01

    Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants. PMID:24126218

  19. High ethanol dose during early adolescence induces locomotor activation and increases subsequent ethanol intake during late adolescence.

    PubMed

    Acevedo, María Belén; Molina, Juan Carlos; Nizhnikov, Michael E; Spear, Norman E; Pautassi, Ricardo Marcos

    2010-07-01

    Adolescent initiation of ethanol consumption is associated with subsequent heightened probability of ethanol use disorders. The present study examined the relationship between motivational sensitivity to ethanol initiation in adolescent rats and later ethanol intake. Experiment 1 determined that ethanol induces locomotor activation shortly after administration but not if tested at a later post-administration interval. In Experiment 2, adolescent rats were assessed for ethanol-induced locomotor activation on postnatal Day 28. These animals were then evaluated for ethanol-mediated conditioned taste aversion and underwent a 16-day-long ethanol intake protocol. Ethanol-mediated aversive effects were unrelated to ethanol locomotor stimulation or subsequent ethanol consumption patterns. Ethanol intake during late adolescence was greatest in animals initiated to ethanol earliest at postnatal Day 28. Females that were more sensitive to ethanol's locomotor-activating effects showed a transient increase in ethanol self-administration. Blood ethanol concentrations during initiation were not related to ethanol-induced locomotor activation. Adolescent rats appeared sensitive to the locomotor-stimulatory effects of ethanol. Even brief ethanol exposure during adolescence may promote later ethanol intake. PMID:20373327

  20. Locomotor Experience Affects Self and Emotion

    ERIC Educational Resources Information Center

    Uchiyama, Ichiro; Anderson, David I.; Campos, Joseph J.; Witherington, David; Frankel, Carl B.; Lejeune, Laure; Barbu-Roth, Marianne

    2008-01-01

    Two studies investigated the role of locomotor experience on visual proprioception in 8-month-old infants. "Visual proprioception" refers to the sense of self-motion induced in a static person by patterns of optic flow. A moving room apparatus permitted displacement of an entire enclosure (except for the floor) or the side walls and ceiling. In…

  1. Neuronal control of locomotor handedness in Drosophila

    PubMed Central

    Buchanan, Sean M.; Kain, Jamey S.; de Bivort, Benjamin L.

    2015-01-01

    Genetically identical individuals display variability in their physiology, morphology, and behaviors, even when reared in essentially identical environments, but there is little mechanistic understanding of the basis of such variation. Here, we investigated whether Drosophila melanogaster displays individual-to-individual variation in locomotor behaviors. We developed a new high-throughout platform capable of measuring the exploratory behavior of hundreds of individual flies simultaneously. With this approach, we find that, during exploratory walking, individual flies exhibit significant bias in their left vs. right locomotor choices, with some flies being strongly left biased or right biased. This idiosyncrasy was present in all genotypes examined, including wild-derived populations and inbred isogenic laboratory strains. The biases of individual flies persist for their lifetime and are nonheritable: i.e., mating two left-biased individuals does not yield left-biased progeny. This locomotor handedness is uncorrelated with other asymmetries, such as the handedness of gut twisting, leg-length asymmetry, and wing-folding preference. Using transgenics and mutants, we find that the magnitude of locomotor handedness is under the control of columnar neurons within the central complex, a brain region implicated in motor planning and execution. When these neurons are silenced, exploratory laterality increases, with more extreme leftiness and rightiness. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality. PMID:25953337

  2. Neuronal control of locomotor handedness in Drosophila.

    PubMed

    Buchanan, Sean M; Kain, Jamey S; de Bivort, Benjamin L

    2015-05-26

    Genetically identical individuals display variability in their physiology, morphology, and behaviors, even when reared in essentially identical environments, but there is little mechanistic understanding of the basis of such variation. Here, we investigated whether Drosophila melanogaster displays individual-to-individual variation in locomotor behaviors. We developed a new high-throughout platform capable of measuring the exploratory behavior of hundreds of individual flies simultaneously. With this approach, we find that, during exploratory walking, individual flies exhibit significant bias in their left vs. right locomotor choices, with some flies being strongly left biased or right biased. This idiosyncrasy was present in all genotypes examined, including wild-derived populations and inbred isogenic laboratory strains. The biases of individual flies persist for their lifetime and are nonheritable: i.e., mating two left-biased individuals does not yield left-biased progeny. This locomotor handedness is uncorrelated with other asymmetries, such as the handedness of gut twisting, leg-length asymmetry, and wing-folding preference. Using transgenics and mutants, we find that the magnitude of locomotor handedness is under the control of columnar neurons within the central complex, a brain region implicated in motor planning and execution. When these neurons are silenced, exploratory laterality increases, with more extreme leftiness and rightiness. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality. PMID:25953337

  3. Extremes of Interferon-Stimulated Gene Expression Associate with Worse Outcomes in the Acute Respiratory Distress Syndrome.

    PubMed

    Nick, Jerry A; Caceres, Silvia M; Kret, Jennifer E; Poch, Katie R; Strand, Matthew; Faino, Anna V; Nichols, David P; Saavedra, Milene T; Taylor-Cousar, Jennifer L; Geraci, Mark W; Burnham, Ellen L; Fessler, Michael B; Suratt, Benjamin T; Abraham, Edward; Moss, Marc; Malcolm, Kenneth C

    2016-01-01

    Acute Respiratory Distress Syndrome (ARDS) severity may be influenced by heterogeneity of neutrophil activation. Interferon-stimulated genes (ISG) are a broad gene family induced by Type I interferons, often as a response to viral infections, which evokes extensive immunomodulation. We tested the hypothesis that over- or under-expression of immunomodulatory ISG by neutrophils is associated with worse clinical outcomes in patients with ARDS. Genome-wide transcriptional profiles of circulating neutrophils isolated from patients with sepsis-induced ARDS (n = 31) and healthy controls (n = 19) were used to characterize ISG expression. Hierarchical clustering of expression identified 3 distinct subject groups with Low, Mid and High ISG expression. ISG accounting for the greatest variability in expression were identified (MX1, IFIT1, and ISG15) and used to analyze a prospective cohort at the Colorado ARDS Network site. One hundred twenty ARDS patients from four urban hospitals were enrolled within 72 hours of initiation of mechanical ventilation. Circulating neutrophils were isolated from patients and expression of ISG determined by PCR. Samples were stratified by standard deviation from the mean into High (n = 21), Mid, (n = 82) or Low (n = 17) ISG expression. Clinical outcomes were compared between patients with High or Low ISG expression to those with Mid-range expression. At enrollment, there were no differences in age, gender, co-existing medical conditions, or type of physiologic injury between cohorts. After adjusting for age, race, gender and BMI, patients with either High or Low ISG expression had significantly worse clinical outcomes than those in the Mid for number of 28-day ventilator- and ICU-free days (P = 0.0006 and 0.0004), as well as 90-day mortality and 90-day home with unassisted breathing (P = 0.02 and 0.004). These findings suggest extremes of ISG expression by circulating neutrophils from ARDS patients recovered early in the syndrome are associated

  4. High Definition Transcranial Direct Current Stimulation Induces Both Acute and Persistent Changes in Broadband Cortical Synchronization: a Simultaneous tDCS-EEG Study

    PubMed Central

    Roy, Abhrajeet; Baxter, Bryan

    2014-01-01

    The goal of this study was to develop methods for simultaneously acquiring electrophysiological data during high definition transcranial direct current stimulation (tDCS) using high resolution electroencephalography (EEG). Previous studies have pointed to the after effects of tDCS on both motor and cognitive performance, and there appears to be potential for using tDCS in a variety of clinical applications. However, little is known about the real-time effects of tDCS on rhythmic cortical activity in humans due to the technical challenges of simultaneously obtaining electrophysiological data during ongoing stimulation. Furthermore, the mechanisms of action of tDCS in humans are not well understood. We have conducted a simultaneous tDCS-EEG study in a group of healthy human subjects. Significant acute and persistent changes in spontaneous neural activity and event related synchronization (ERS) were observed during and after the application of high definition tDCS over the left sensorimotor cortex. Both anodal and cathodal stimulation resulted in acute global changes in broadband cortical activity which were significantly different than the changes observed in response to sham stimulation. For the group of 8 subjects studied, broadband individual changes in spontaneous activity during stimulation were apparent both locally and globally. In addition, we found that high definition tDCS of the left sensorimotor cortex can induce significant ipsilateral and contralateral changes in event related desynchronization (ERD) and ERS during motor imagination following the end of the stimulation period. Overall, our results demonstrate the feasibility of acquiring high resolution EEG during high definition tDCS and provide evidence that tDCS in humans directly modulates rhythmic cortical synchronization during and after its administration. PMID:24956615

  5. Fostering Locomotor Behavior of Children with Developmental Disabilities: An Overview of Studies Using Treadmills and Walkers with Microswitches

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Didden, Robert; Manfredi, Francesco; Putignano, Pietro; Stasolla, Fabrizio; Basili, Gabriella

    2009-01-01

    This paper provides an overview of studies using programs with treadmills or walkers with microswitches and contingent stimulation to foster locomotor behavior of children with developmental disabilities. Twenty-six studies were identified in the period 2000-2008 (i.e., the period in which research in this area has actually taken shape).…

  6. An Epstein-Barr Virus Encoded Inhibitor of Colony Stimulating Factor-1 Signaling Is an Important Determinant for Acute and Persistent EBV Infection

    PubMed Central

    Ohashi, Makoto; Fogg, Mark H.; Orlova, Nina; Quink, Carol; Wang, Fred

    2012-01-01

    Acute Epstein-Barr virus (EBV) infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1) signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV), naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1). Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection. PMID:23300447

  7. Distinct inhibition of acute cocaine-stimulated motor activity following microinjection of a group III metabotropic glutamate receptor agonist into the dorsal striatum of rats.

    PubMed

    Mao, L; Wang, J Q

    2000-09-01

    Group III metabotropic glutamate receptors (mGluRs) are negatively coupled to adenylate cyclase through G-proteins. Activation of this group of mGluRs shows an inhibition of dopaminergic transmission in the forebrain. To define the role of striatal group III mGluRs in the regulation of basal and dopamine-stimulated motor behavior, the recently developed agonist and antagonist relatively selective for group III mGluRs were utilized to pharmacologically enhance and reduce group III mGluR glutamatergic tone in the dorsal striatum of chronically cannulated rats. Bilateral injections of a group III agonist, L-2-amino-4-phosphonobutyrate (L-AP4), did not alter basal levels of motor activity at three doses surveyed (1, 10, and 100 nmol). Neither did intracaudate injection of a group III antagonist, alpha-methyl-4-phosphonophenylglycine (MPPG), at 10, 30, and 100 nmol. However, pretreatment with L-AP4 (10 and 100 nmol) dose dependently blocked hyperlocomotion induced by acute injection of cocaine (20 mg/kg, i.p.), amphetamine (2.5 mg/kg, i.p.), or apomorphine (1 mg/kg, s.c.). The behavioral activity induced by cocaine was much more sensitive to L-AP4 than that induced by amphetamine and apomorphine. At 100 nmol, L-AP4 completely blocked cocaine effect whereas amphetamine- and apomorphine-stimulated behaviors were blocked only by 28% and 31%, respectively. The blocking effect of L-AP4 on cocaine action was reversed by pretreatment with MPPG. MPPG itself did not modify behavioral responses to cocaine, amphetamine, or apomorphine. These data indicate that the glutamatergic tone on the group III mGluRs is not active in the regulation of basal and acute dopamine-stimulated motor activity. However, enhanced group III mGluR glutamatergic transmission by an exogenous ligand is capable of suppressing behavioral responses to acute exposure of dopamine stimulants. PMID:11113488

  8. A Novel Substituted Piperazine, CM156, Attenuates the Stimulant and Toxic Effects of Cocaine in Mice

    PubMed Central

    Xu, Yan-Tong; Kaushal, Nidhi; Shaikh, Jamaluddin; Wilson, Lisa L.; Mésangeau, Christophe; McCurdy, Christopher R.

    2010-01-01

    Cocaine is a highly abused drug without effective pharmacotherapies to treat it. It interacts with sigma (σ) receptors, providing logical targets for the development of medications to counteract its actions. Cocaine causes toxic and stimulant effects that can be categorized as acute effects such as convulsions and locomotor hyperactivity and subchronic effects including sensitization and place conditioning. In the present study, 3-(4-(4-cyclohexylpiperazin-1-yl)butyl)benzo[d]thiazole-2(3H)-thione (CM156), a novel compound, was developed and tested for interactions with σ receptors using radioligand binding studies. It was also evaluated against cocaine-induced effects in behavioral studies. The results showed that CM156 has nanomolar affinities for each of the σ receptor subtypes in the brain and much weaker affinities for non-σ binding sites. Pretreatment of male Swiss-Webster mice with CM156, before administering either a convulsive or locomotor stimulant dose of cocaine, led to a significant attenuation of these acute effects. CM156 also significantly reduced the expression of behavioral sensitization and place conditioning evoked by subchronic exposure to cocaine. The protective effects of CM156 are consistent with σ receptor-mediated actions. Together with previously reported findings, the data from CM156 and related σ compounds indicate that σ receptors can be targeted to alleviate deleterious actions of cocaine. PMID:20100904

  9. The evolution of locomotor rhythmicity in tetrapods.

    PubMed

    Ross, Callum F; Blob, Richard W; Carrier, David R; Daley, Monica A; Deban, Stephen M; Demes, Brigitte; Gripper, Janaya L; Iriarte-Diaz, Jose; Kilbourne, Brandon M; Landberg, Tobias; Polk, John D; Schilling, Nadja; Vanhooydonck, Bieke

    2013-04-01

    Differences in rhythmicity (relative variance in cycle period) among mammal, fish, and lizard feeding systems have been hypothesized to be associated with differences in their sensorimotor control systems. We tested this hypothesis by examining whether the locomotion of tachymetabolic tetrapods (birds and mammals) is more rhythmic than that of bradymetabolic tetrapods (lizards, alligators, turtles, salamanders). Species averages of intraindividual coefficients of variation in cycle period were compared while controlling for gait and substrate. Variance in locomotor cycle periods is significantly lower in tachymetabolic than in bradymetabolic animals for datasets that include treadmill locomotion, non-treadmill locomotion, or both. When phylogenetic relationships are taken into account the pooled analyses remain significant, whereas the non-treadmill and the treadmill analyses become nonsignificant. The co-occurrence of relatively high rhythmicity in both feeding and locomotor systems of tachymetabolic tetrapods suggests that the anatomical substrate of rhythmicity is in the motor control system, not in the musculoskeletal components. PMID:23550769

  10. Locomotor training modifies soleus monosynaptic motoneuron responses in human spinal cord injury

    PubMed Central

    Smith, Andrew C.; Rymer, William Zev

    2015-01-01

    The objective of this study was to assess changes in monosynaptic motoneuron responses to stimulation of Ia afferents after locomotor training in individuals with chronic spinal cord injury (SCI). We hypothesized that locomotor training modifies the amplitude of the soleus monosynaptic motoneuron responses in a body position-dependent manner. Fifteen individuals with chronic clinical motor complete or incomplete SCI received an average of 45 locomotor training sessions. The soleus H-reflex and M-wave recruitment curves were assembled using data collected in both the right and left legs, with subjects seated and standing, before and after training. The soleus H-reflexes and M-waves, measured as peak-to-peak amplitudes, were normalized to the maximal M-wave (Mmax). Stimulation intensities were normalized to 50 % Mmax stimulus intensity. A sigmoid function was also fitted to the normalized soleus H-reflexes on the ascending limb of the recruitment curve. After training, soleus H-reflex excitability was increased in both legs in AIS C subjects, and remained unchanged in AIS A-B and AIS D subjects during standing. When subjects were seated, soleus H-reflex excitability was decreased after training in many AIS C and D subjects. Changes in reflex excitability coincided with changes in stimulation intensities at H-threshold, 50 % maximal H-reflex, and at maximal H-reflex, while an interaction between leg side and AIS scale for the H-reflex slope was also found. Adaptations of the intrinsic properties of soleus motoneurons and Ia afferents, the excitability profile of the soleus motoneuron pool, oligosynaptic inputs, and corticospinal inputs may all contribute to these changes. The findings of this study demonstrate that locomotor training impacts the amplitude of the monosynaptic motoneuron responses based on the demands of the motor task in people with chronic SCI. PMID:25205562

  11. 810nm near-infrared light offers neuroprotection and improves locomotor activity in MPTP-treated mice.

    PubMed

    Reinhart, Florian; Massri, Nabil El; Darlot, Fannie; Torres, Napoleon; Johnstone, Daniel M; Chabrol, Claude; Costecalde, Thomas; Stone, Jonathan; Mitrofanis, John; Benabid, Alim-Louis; Moro, Cécile

    2015-03-01

    We explored whether 810nm near-infrared light (NIr) offered neuroprotection and/or improvement in locomotor activity in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease. Mice received MPTP and 810nm NIr treatments, or not, and were tested for locomotive activity in an open-field test. Thereafter, brains were aldehyde-fixed and processed for tyrosine hydroxylase immunohistochemistry. Our results showed that MPTP-treated mice that were irradiated with 810nm NIr had both greater locomotor activity (∼40%) and number of dopaminergic cells (∼20%) than those that were not. In summary, 810nm (as with 670nm) NIr offered neuroprotection and improved locomotor activity in MPTP-treated mice. PMID:25462595

  12. Dose-dependent changes in the synaptic strength on dopamine neurons and locomotor activity after cocaine exposure

    PubMed Central

    Wanat, M.J.; Bonci, A.

    2016-01-01

    Changes in synaptic strength on ventral tegmental area (VTA) dopamine neurons are thought to play a critical role in the development of addiction-related behaviors. However, it is unknown how a single injection of cocaine at different doses affects locomotor activity, behavioral sensitization, and glutamatergic synaptic strength on VTA dopamine neurons in mice. We observed that behavioral sensitization to a challenge cocaine injection scaled with the dose of cocaine received one day prior. Interestingly, the locomotor activity after the initial exposure to different doses of cocaine corresponded to the changes in glutamatergic strength on VTA dopamine neurons. These results in mice suggest that a single exposure to cocaine dose-dependently affects excitatory synapses on VTA dopamine neurons, and that this acute synaptic alteration is directly associated with the locomotor responses to cocaine and not to behavioral sensitization. PMID:18655120

  13. Melanin-concentrating hormone is necessary for olanzapine-inhibited locomotor activity in male mice.

    PubMed

    Chee, Melissa J S; Douris, Nicholas; Forrow, Avery B; Monnard, Arnaud; Lu, Shuangyu; Flaherty, Stephen E; Adams, Andrew C; Maratos-Flier, Eleftheria

    2015-10-01

    Olanzapine (OLZ), an atypical antipsychotic, can be effective in treating patients with restricting type anorexia nervosa who exercise excessively. Clinical improvements include weight gain and reduced pathological hyperactivity. However the neuronal populations and mechanisms underlying OLZ actions are not known. We studied the effects of OLZ on hyperactivity using male mice lacking the hypothalamic neuropeptide melanin-concentrating hormone (MCHKO) that are lean and hyperactive. We compared the in vivo effects of systemic or intra-accumbens nucleus (Acb) OLZ administration on locomotor activity in WT and MCHKO littermates. Acute systemic OLZ treatment in WT mice significantly reduced locomotor activity, an effect that is substantially attenuated in MCHKO mice. Furthermore, OLZ infusion directly into the Acb of WT mice reduced locomotor activity, but not in MCHKO mice. To identify contributing neuronal mechanisms, we assessed the effect of OLZ treatment on Acb synaptic transmission ex vivo and in vitro. Intraperitoneal OLZ treatment reduced Acb GABAergic activity in WT but not MCHKO neurons. This effect was also seen in vitro by applying OLZ to acute brain slices. OLZ reduced the frequency and amplitude of GABAergic activity that was more robust in WT than MCHKO Acb. These findings indicate that OLZ reduced Acb GABAergic transmission and that MCH is necessary for the hypolocomotor effects of OLZ. PMID:26092201

  14. Separate and combined impact of acute naltrexone and alprazolam on subjective and physiological effects of oral d-amphetamine in stimulant users

    PubMed Central

    Marks, Katherine R.; Lile, Joshua A.; Stoops, William W.

    2014-01-01

    Rationale Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric-acidA (GABAA) receptors (e.g., alprazolam) modestly attenuate the abuse-related effects of stimulants like amphetamine. The use of higher doses to achieve greater efficacy is precluded by side effects. Combining naltrexone and alprazolam might safely maximize efficacy while avoiding the untoward effects of the constituent compounds. Objectives The present pilot study tested the hypothesis that acute pretreatment with the combination of naltrexone and alprazolam would not produce clinically problematic physiological effects or negative subjective effects and would reduce the positive subjective effects of d-amphetamine to a greater extent than the constituent drugs alone. Methods Eight nontreatment-seeking, stimulant-using individuals completed an outpatient experiment in which oral d-amphetamine (0, 15, and 30 mg) was administered following acute pretreatment with naltrexone (0 and 50 mg) and alprazolam (0 and 0.5 mg). Subjective effects, psychomotor task performance, and physiological measures were collected. Results Oral d-amphetamine produced prototypical physiological and stimulant-like positive subjective effects (e.g., VAS ratings of Active/Alert/Energetic, Good Effect, and High). Pretreatment with naltrexone, alprazolam, and their combination did not produce clinically problematic acute physiological effects or negative subjective effects. Naltrexone and alprazolam each significantly attenuated some of the subjective effects of d-amphetamine. The combination attenuated a greater number of subjective effects than the constituent drugs alone. Conclusions The present results support the continued evaluation of an opioid receptor antagonist combined with a GABAA-positive modulator using more clinically relevant experimental conditions like examining the effect of chronic dosing with these drugs on methamphetamine self-administration. PMID:24464531

  15. Effects of coal mine wastewater on locomotor and non-locomotor activities of empire gudgeons (Hypseleotris compressa).

    PubMed

    Lanctôt, C; Melvin, S D; Fabbro, L; Leusch, F D L; Wilson, S P

    2016-05-01

    Coal mining represents an important industry in many countries, but concerns exist about the possible adverse effects of minewater releases on aquatic animals and ecosystems. Coal mining generates large volumes of complex wastewater, which often contains high concentrations of dissolved solids, suspended solids, metals, hydrocarbons, salts and other compounds. Traditional toxicological testing has generally involved the assessment of acute toxicity or chronic toxicity with longer-term tests, and while such tests provide useful information, they are poorly suited to ongoing monitoring or rapid assessment following accidental discharge events. As such, there is considerable interest in developing rapid and sensitive approaches to environmental monitoring, and particularly involving the assessment of sub-lethal behavioural responses in locally relevant aquatic species. We therefore investigated behavioural responses of a native Australian fish to coal mine wastewater, to evaluate its potential use for evaluating sub-lethal effects associated with wastewater releases on freshwater ecosystems. Empire gudgeons (Hypseleotris compressa) were exposed to wastewater from two dams located at an open cut coal mine in Central Queensland, Australia and activity levels were monitored using the Multispecies Freshwater Biomonitor® (LimCo International GmbH). A general decrease in locomotor activity (i.e., low frequency movement) and increase in non-locomotor activity (i.e., high frequency movement including ventilation and small fin movement) was observed in exposed fish compared to those in control water. Altered activity levels were observable within the first hour of exposure and persisted throughout the 15-d experiment. Results demonstrate the potential for using behavioural endpoints as tools for monitoring wastewater discharges using native fish species, but more research is necessary to identify responsible compounds and response thresholds, and to understand the relevance

  16. Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study...

  17. Effects of 3-O-methyldopa, L-3,4-dihydroxyphenylalanine metabolite, on locomotor activity and dopamine turnover in rats.

    PubMed

    Onzawa, Yoritaka; Kimura, Yasuhiro; Uzuhashi, Kengo; Shirasuna, Megumi; Hirosawa, Tasuku; Taogoshi, Takanori; Kihira, Kenji

    2012-01-01

    It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson's disease (PD) patients receiving long term L-DOPA therapy. However, the physiological role of 3-OMD has not been well understood. Therefore, in order to clarify the effects of 3-OMD on physiological function, we examined the behavioral alteration in rats based on locomotor activity, and measured dopamine (DA) and its metabolites levels in rats at the same time after 3-OMD subchronic administration. The study results showed that repeated administrations of 3-OMD increased its blood and the striatum tissue levels in those rats, and decreased locomotor activity in a dose dependent manner. Although 3-OMD subchronic administration showed no significant change in DA level in the striatum, DA metabolite levels, such as 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were significantly decreased. After 3-OMD washout period (7 d), locomotor activity and DA turnover in those rats returned to normal levels. Furthermore, locomotor activity and DA turnover decreased by 3-OMD administration were recovered to normal level by acute L-DOPA administration. These results suggested that 3-OMD affect to locomotor activity via DA neuron system. In conclusion, 3-OMD itself may have a disadvantage in PD patients receiving L-DOPA therapy. PMID:22863920

  18. Evidence That GABA Mediates Dopaminergic and Serotonergic Pathways Associated with Locomotor Activity in Juvenile Chinook Salmon (Oncorhynchus tshawytscha)

    USGS Publications Warehouse

    Clements, S.; Schreck, C.B.

    2004-01-01

    The authors examined the control of locomotor activity in juvenile salmon (Oncorhynchus tshawytscha) by manipulating 3 neurotransmitter systems-gamma-amino-n-butyric acid (GABA), dopamine, and serotonin-as well as the neuropeptide corticotropin releasing hormone (CRH). Intracerebroventricular (ICV) injections of CRH and the GABAAagonist muscimol stimulated locomotor activity. The effect of muscimol was attenuated by administration of a dopamine receptor antagonist, haloperidol. Conversely, the administration of a dopamine uptake inhibitor (4???,4??? -difluoro-3-alpha-[diphenylmethoxy] tropane hydrochloride [DUI]) potentiated the effect of muscimol. They found no evidence that CRH-induced hyperactivity is mediated by dopaminergic systems following concurrent injections of haloperidol or DUI with CRH. Administration of muscimol either had no effect or attenuated the locomotor response to concurrent injections of CRH and fluoxetine, whereas the GABAA antagonist bicuculline methiodide potentiated the effect of CRH and fluoxetine.

  19. Dynamics of the locomotor-respiratory coupling at different frequencies.

    PubMed

    Hoffmann, Charles P; Bardy, Benoît G

    2015-05-01

    The locomotor-respiratory coupling (LRC) is a universal phenomenon reported for various forms of rhythmic exercise. In this study, we investigated the effect of movement and respiratory frequencies on LRC. Participants were instructed to cycle or breath in synchrony with a periodic auditory stimulation at preferred and non-preferred frequencies. LRC stability was assessed by frequency and phase coupling indexes using the theory of nonlinear coupled oscillators through the sine circle map model, and the Farey tree. Results showed a stabilizing effect of sound on LRC for all frequencies and for the two systems paced. The sound-induced effect was more prominent when the rhythm of the stimulation corresponded to the preferred frequencies. The adoption of cycling or respiratory frequencies far off preferential ones led to a loss of stability in LRC. Contrary to previous findings, our results suggest that LRC is not unidirectional-from locomotion onto respiration-but bidirectional between the two systems. They also suggest that auditory information plays an important role in the modulation of LRC. PMID:25796188

  20. Bimodal Respiratory-Locomotor Neurons in the Neonatal Rat Spinal Cord.

    PubMed

    Le Gal, Jean-Patrick; Juvin, Laurent; Cardoit, Laura; Morin, Didier

    2016-01-20

    Neural networks that can generate rhythmic motor output in the absence of sensory feedback, commonly called central pattern generators (CPGs), are involved in many vital functions such as locomotion or respiration. In certain circumstances, these neural networks must interact to produce coordinated motor behavior adapted to environmental constraints and to satisfy the basic needs of an organism. In this context, we recently reported the existence of an ascending excitatory influence from lumbar locomotor CPG circuitry to the medullary respiratory networks that is able to depolarize neurons of the parafacial respiratory group during fictive locomotion and to subsequently induce an increased respiratory rhythmicity (Le Gal et al., 2014b). Here, using an isolated in vitro brainstem-spinal cord preparation from neonatal rat in which the respiratory and the locomotor networks remain intact, we show that during fictive locomotion induced either pharmacologically or by sacrocaudal afferent stimulation, the activity of both thoracolumbar expiratory motoneurons and interneurons is rhythmically modulated with the locomotor activity. Completely absent in spinal inspiratory cells, this rhythmic pattern is highly correlated with the hindlimb ipsilateral flexor activities. Furthermore, silencing brainstem neural circuits by pharmacological manipulation revealed that this locomotor-related drive to expiratory motoneurons is solely dependent on propriospinal pathways. Together these data provide the first evidence in the newborn rat spinal cord for the existence of bimodal respiratory-locomotor motoneurons and interneurons onto which both central efferent expiratory and locomotor drives converge, presumably facilitating the coordination between the rhythmogenic networks responsible for two different motor functions. Significance statement: In freely moving animals, distant regions of the brain and spinal cord controlling distinct motor acts must interact to produce the best

  1. Changes in cell death of peripheral blood lymphocytes isolated from children with acute lymphoblastic leukemia upon stimulation with 7 Hz, 30 mT pulsed electromagnetic field.

    PubMed

    Kaszuba-Zwoińska, Jolanta; Ćwiklińska, Magdalena; Balwierz, Walentyna; Chorobik, Paulina; Nowak, Bernadeta; Wójcik-Piotrowicz, Karolina; Ziomber, Agata; Malina-Novak, Kinga; Zaraska, Wiesław; Thor, Piotr J

    2015-03-01

    Pulsed electromagnetic field (PEMF) influenced the viability of proliferating in vitro peripheral blood mononuclear cells (PBMCs) isolated from Crohn's disease patients as well as acute myeloblastic leukemia (AML) patients by induction of cell death, but did not cause any vital changes in cells from healthy donors. Experiments with lymphoid U937 and monocytic MonoMac6 cell lines have shown a protective effect of PEMF on the death process in cells treated with death inducers. The aim of the current study was to investigate the influence of PEMF on native proliferating leukocytes originating from newly diagnosed acute lymphoblastic leukemia (ALL) patients. The effects of exposure to PEMF were studied in PBMCs from 20 children with ALL. PBMCs were stimulated with three doses of PEMF (7 Hz, 30 mT) for 4 h each with 24 h intervals. After the last stimulation, the cells were double stained with annexin V and propidium iodide dye to estimate viability by flow cytometric analysis. The results indicated an increase of annexin V positive as well as double stained annexin V and propidium iodide positive cells after exposure to threefold PEMF stimulation. A low-frequency pulsed electromagnetic field induces cell death in native proliferating cells isolated from ALL patients. The increased vulnerability of proliferating PBMCs to PEMF-induced interactions may be potentially applied in the therapy of ALL. The analysis of expression of apoptosis-related genes revealed changes in mRNA of some genes engaged in the intrinsic apoptotic pathway belonging to the Bcl-2 family and the pathway with apoptosis-inducing factor (AIF) abundance upon PEMF stimulation of PBMCs. PMID:26204398

  2. Involvement of spinal α2 -adrenoceptors in prolonged modulation of hind limb withdrawal reflexes following acute noxious stimulation in the anaesthetized rabbit.

    PubMed

    Harris, John

    2016-03-01

    The role of spinal α2 -adrenoceptors in mediating long-lasting modulation of hind limb withdrawal reflexes following acute noxious chemical stimulation of distant heterotopic and local homotopic locations has been investigated in pentobarbitone-anaesthetized rabbits. Reflexes evoked in the ankle extensor muscle medial gastrocnemius (MG) by electrical stimulation of the ipsilateral heel, and reflexes elicited in the ankle flexor tibialis anterior and the knee flexor semitendinosus by stimulation at the base of the ipsilateral toes, could be inhibited for over 1 h after mustard oil (20%) was applied to either the snout or into the contralateral MG. The heel-MG response was also inhibited after applying mustard oil across the plantar metatarsophalangeal joints of the ipsilateral foot, whereas this homotopic stimulus facilitated both flexor responses. Mustard oil also caused a significant pressor effect when applied to any of the three test sites. The selective α2 -adrenoceptor antagonist, RX 821002 (100-300 μg, intrathecally), had no effect on reflexes per se, but did cause a decrease in mean arterial blood pressure. In the presence of the α2 -blocker, inhibitory and facilitatory effects of mustard oil on reflexes were completely abolished. These data imply that long-lasting inhibition of spinal reflexes following acute noxious stimulation of distant locations involves activation of supraspinal noradrenergic pathways, the effects of which are dependent on an intact α2 -adrenoceptor system at the spinal level. These pathways and receptors also appear to be involved in facilitation (sensitization) as well as inhibition of reflexes following a noxious stimulus applied to the same limb. PMID:26804327

  3. A parallel cholinergic brainstem pathway for enhancing locomotor drive

    PubMed Central

    Smetana, Roy; Juvin, Laurent; Dubuc, Réjean; Alford, Simon

    2010-01-01

    The brainstem locomotor system is believed to be organized serially from the mesencephalic locomotor region (MLR) to reticulospinal neurons, which in turn, project to locomotor neurons in the spinal cord. In contrast, we now identify in lampreys, brainstem muscarinoceptive neurons receiving parallel inputs from the MLR and projecting back to reticulospinal cells to amplify and extend durations of locomotor output. These cells respond to muscarine with extended periods of excitation, receive direct muscarinic excitation from the MLR, and project glutamatergic excitation to reticulospinal neurons. Targeted block of muscarine receptors over these neurons profoundly reduces MLR-induced excitation of reticulospinal neurons and markedly slows MLR-evoked locomotion. Their presence forces us to rethink the organization of supraspinal locomotor control, to include a sustained feedforward loop that boosts locomotor output. PMID:20473293

  4. Development of Testing Methodologies to Evaluate Postflight Locomotor Performance

    NASA Technical Reports Server (NTRS)

    Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Warren, L. E.; Bloomberg, J. J.

    2006-01-01

    Crewmembers experience locomotor and postural instabilities during ambulation on Earth following their return from space flight. Gait training programs designed to facilitate recovery of locomotor function following a transition to a gravitational environment need to be accompanied by relevant assessment methodologies to evaluate their efficacy. The goal of this paper is to demonstrate the operational validity of two tests of locomotor function that were used to evaluate performance after long duration space flight missions on the International Space Station (ISS).

  5. DeltaFosB induction in orbitofrontal cortex potentiates locomotor sensitization despite attenuating the cognitive dysfunction caused by cocaine.

    PubMed

    Winstanley, Catharine A; Green, Thomas A; Theobald, David E H; Renthal, William; LaPlant, Quincey; DiLeone, Ralph J; Chakravarty, Sumana; Nestler, Eric J

    2009-09-01

    The effects of addictive drugs change with repeated use: many individuals become tolerant of their pleasurable effects but also more sensitive to negative sequelae (e.g., anxiety, paranoia, and drug craving). Understanding the mechanisms underlying such tolerance and sensitization may provide valuable insight into the basis of drug dependency and addiction. We have recently shown that chronic cocaine administration reduces the ability of an acute injection of cocaine to affect impulsivity in rats. However, animals become more impulsive during withdrawal from cocaine self-administration. We have also shown that chronic administration of cocaine increases expression of the transcription factor DeltaFosB in the orbitofrontal cortex (OFC). Mimicking this drug-induced elevation in OFC DeltaFosB through viral-mediated gene transfer mimics these behavioural changes: DeltaFosB over-expression in OFC induces tolerance to the effects of an acute cocaine challenge but sensitizes rats to the cognitive sequelae of withdrawal. Here we report novel data demonstrating that increasing DeltaFosB in the OFC also sensitizes animals to the locomotor-stimulant properties of cocaine. Analysis of nucleus accumbens tissue taken from rats over-expressing DeltaFosB in the OFC and treated chronically with saline or cocaine does not provide support for the hypothesis that increasing OFC DeltaFosB potentiates sensitization via the nucleus accumbens. These data suggest that both tolerance and sensitization to cocaine's many effects, although seemingly opposing processes, can be induced in parallel via the same biological mechanism within the same brain region, and that drug-induced changes in gene expression within the OFC play an important role in multiple aspects of addiction. PMID:19135469

  6. Cross-sensitization between cocaine and acute restraint stress is associated with sensitized dopamine but not glutamate release in the nucleus accumbens.

    PubMed

    Garcia-Keller, C; Martinez, S A; Esparza, M A; Bollati, F; Kalivas, P W; Cancela, L M

    2013-03-01

    Repeated administration of psychostimulant drugs or stress can elicit a sensitized response to the stimulating and reinforcing properties of the drug. Here we explore the mechanisms in the nucleus accumbens (NAc) whereby an acute restraint stress augments the acute locomotor response to cocaine. This was accomplished by a combination of behavioral pharmacology, microdialysis measures of extracellular dopamine and glutamate, and Western blotting for GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor (AMPAR). A single exposure to restraint stress 3 weeks before testing revealed that enduring locomotor sensitization to cocaine was paralleled by an increase in extracellular dopamine in the core, but not the shell subcompartment, of the NAc. Wistar rats pre-exposed to acute stress showed increased basal levels of glutamate in the core, but the increase in glutamate by acute cocaine was blunted. The alterations in extracellular glutamate seem to be relevant, as blocking AMPAR by 6-cyano-7-nitroquinoxaline-2,3-dione microinjection into the core prevented both the behavioral cross-sensitization and the augmented increase in cocaine-induced extracellular dopamine. Further implicating glutamate, the locomotor response to AMPAR stimulation in the core was potentiated, but not in the shell of pre-stressed animals, and this was accompanied by an increase in NAc GluR1 surface expression. This study provides evidence that the long-term expression of restraint stress-induced behavioral cross-sensitization to cocaine recapitulates some mechanisms thought to underpin the sensitization induced by daily cocaine administration, and shows that long-term neurobiological changes induced in the NAc by acute stress are consequential in the expression of cross-sensitization to cocaine. PMID:23360446

  7. Modelling the locomotor energetics of extinct hominids.

    PubMed

    Kramer, P A

    1999-10-01

    Bipedality is the defining characteristic of Hominidae and, as such, an understanding of the adaptive significance and functional implications of bipedality is imperative to any study of human evolution. Hominid bipedality is, presumably, a solution to some problem for the early hominids, one that has much to do with energy expenditure. Until recently, however, little attention could be focused on the quantifiable energetic aspects of bipedality as a unique locomotor form within Primates because of the inability to measure empirically the energy expenditure of non-modern hominids. A recently published method provides a way of circumventing the empirical measurement dilemma by calculating energy expenditure directly from anatomical variables and movement profiles. Although the origins of bipedality remain clouded, two discernible forms of locomotor anatomy are present in the hominid fossil record: the australopithecine and modern configurations. The australopithecine form is best represented by AL 288-1, a partial skeleton of Australopithecus afarensis, and is characterized as having short legs and a wide pelvis. The modern form is represented by modern humans and has long legs and a narrow pelvis. Human walking is optimized to take advantage of the changing levels of potential and kinetic energy that occur as the body and limbs move through the stride cycle. Although this optimization minimizes energy expenditure, some energy is required to maintain motion. I quantify this energy by developing a dynamic model that uses kinematic equations to determine energy expenditure. By representing both configurations with such a model, I can compare their rates of energy expenditure. I find that the australopithecine configuration uses less energy than that of a modern human. Despite arguments presented in the anthropological literature, the shortness of the legs of AL 288-1 provides no evidence that she was burdened with a compromised or transitional locomotor anatomy

  8. Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate-mediated attenuation.

    PubMed

    Del Rio, Carlos L; Dawson, Tom A; Clymer, Bradley D; Paterson, David J; Billman, George E

    2008-08-01

    Parasympathetic activity during acute coronary artery occlusion (CAO) can protect against ischaemia-induced malignant arrhythmias; nonetheless, the mechanism mediating this protection remains unclear. During CAO, myocardial electrotonic uncoupling is associated with autonomically mediated immediate (i.e. type 1A) arrhythmias and can modulate pro-arrhythmic dispersion of repolarization. Therefore, the effects of acutely enhanced or decreased cardiac parasympathetic activity on early electrotonic coupling during CAO, as measured by myocardial electrical impedance (MEI), were investigated. Anaesthetized dogs were instrumented for MEI measurements, and left circumflex coronary arterial occlusions were performed in intact (CTRL) and vagotomized (VAG) animals. The CAO was followed by either vagotomy (CTRL) or vagal nerve stimulation (VNS, 10 Hz, 10 V) in the VAG dogs. Vagal nerve stimulation was studied in two additional sets of animals. In one set heart rate (HR) was maintained by pacing (220 beats min(-1)), while in the other set bilateral stellectomy preceded CAO. The MEI increased after CAO in all animals. A larger MEI increase was observed in vagotomized animals (+85 +/- 9 Omega, from 611 +/- 24 Omega, n = 16) when compared with intact control dogs (+43 +/- 5 Omega, from 620 +/- 20 Omega, n = 7). Acute vagotomy during ischaemia abruptly increased HR (from 155 +/- 11 to 193 +/- 15 beats min(-1)) and MEI (+12 +/- 1.1 Omega, from 663 +/- 18 Omega). In contrast, VNS during ischaemia (n = 11) abruptly reduced HR (from 206 +/- 6 to 73 +/- 9 beats min(-1)) and MEI (-16 +/- 2 Omega, from 700 +/- 44 Omega). These effects of VNS were eliminated by pacing but not by bilateral stellectomy. Vagal nerve stimulation during CAO also attenuated ECG-derived indices of ischaemia (e.g. ST segment, 0.22 +/- 0.03 versus 0.15 +/- 0.03 mV) and of rate-corrected repolarization dispersion [terminal portion of T wave (TPEc), 84.5 +/- 4.2 versus 65.8 +/- 5.9 ms; QTc, 340 +/- 8 versus 254

  9. Synthetic cathinone MDPV downregulates glutamate transporter subtype I (GLT-1) and produces rewarding and locomotor-activating effects that are reduced by a GLT-1 activator.

    PubMed

    Gregg, Ryan A; Hicks, Callum; Nayak, Sunil U; Tallarida, Christopher S; Nucero, Paul; Smith, Garry R; Reitz, Allen B; Rawls, Scott M

    2016-09-01

    Synthetic cathinones produce dysregulation of monoamine systems, but their effects on the glutamate system and the influence of glutamate on behavioral effects related to cathinone abuse are unknown. A principal regulator of glutamate homeostasis is glutamate transporter subtype 1 (GLT-1), an astrocytic protein that clears glutamate from the extracellular space and influences behavioral effects of established psychostimulants. We hypothesized that repeated administration of the synthetic cathinone, MDPV (3,4-methylenedioxypyrovalerone), would affect GLT-1 expression in the corticolimbic circuit, and that a GLT-1 activator (ceftriaxone, CTX) would reduce rewarding and locomotor-stimulant effects of MDPV in rats. GLT-1 protein expression in the nucleus accumbens (NAcc), but not prefrontal cortex (PFC), was decreased following withdrawal (2, 5 and 10 days) from repeated MDPV treatment, but not immediately after the last MDPV injection. CTX (200 mg/kg) pretreatment did not affect acute locomotor activation produced by MDPV (0.5, 1, 3 mg/kg). However, CTX (200 mg/kg) administered during a 7-day MDPV treatment paradigm attenuated the development of MDPV-induced sensitization of repetitive movements in rats challenged with MDPV following 11 days of drug abstinence. Pretreatment with CTX (200 mg/kg) during a 4-day MDPV (2 mg/kg) conditioned place preference (CPP) paradigm reduced the development of place preference produced by MDPV. The present data demonstrate dysregulation of corticolimbic glutamate transport systems during withdrawal from chronic MDPV exposure, and show that a GLT-1 transporter activator disrupts behavioral effects of MDPV that are related to synthetic cathinone abuse. PMID:27085607

  10. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

    PubMed Central

    Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2014-01-01

    Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies. PMID:24917788

  11. 131I-MIBG targeting of neuroblastoma cells is acutely enhanced by KCl stimulation through the calcium/calmodulin-dependent kinase pathway.

    PubMed

    Chung, Hyun Woo; Park, Jin Won; Lee, Eun Jeong; Jung, Kyung-Ho; Paik, Jin-Young; Lee, Kyung-Han

    2013-01-01

    The efficacy of (131)I-metaiodobenzylguanidine (MIBG) therapy relies on norepinephrine transporter (NET) function. The ionic make-up of the extracellular fluid critically controls neuronal cell activity and can also affect substrate transport. In this study, we explored the effect of treatment with elevated KCl concentration on MIBG uptake in SK-N-SH neuroblastoma cells. KCl stimulation caused a rapid increase of (131)I-MIBG uptake in a manner that was calcium-dependent and accompanied by activation of calcium/calmodulin-dependent protein kinase (CaMK)II. The effect was completely abolished by KN93, an inhibitor of CaMKI, II, and IV. STO609, a selective inhibitor of CaMK kinase required for activation of CaMKI and IV, but not CaMKII, only modestly attenuated the response. The KCl effect was also completely abrogated by ML7, a selective inhibitor of myosin light chain kinase (MLCK). This restricted form of CaMK activates myosin, which is required for vesicle trafficking. Saturation kinetic analysis revealed KCl stimulation to increase maximal transport velocity without affecting substrate affinity. In conclusion, KCl stimulation rapidly upregulates NET function through the CaMK pathway via activation of CaMKII and MLCK. These findings allow a better understanding of how NET function is acutely modulated by the ionic environment, which in turn may ultimately help improve the efficacy of (131)I-MIBG therapy. PMID:23763646

  12. Weak Power Frequency Magnetic Field Acting Similarly to EGF Stimulation, Induces Acute Activations of the EGFR Sensitive Actin Cytoskeleton Motility in Human Amniotic Cells

    PubMed Central

    Wu, Xia; Cao, Mei-Ping; Shen, Yun-Yun; Chu, Ke-Ping; Tao, Wu-Bin; Song, Wei-Tao; Liu, Li-Ping; Wang, Xiang-Hui; Zheng, Yu-Fang; Chen, Shu-De; Zeng, Qun-Li; Xia, Ruo-Hong

    2014-01-01

    In this article, we have examined the motility-related effects of weak power frequency magnetic fields (MFs) on the epidermal growth factor receptor (EGFR)-sensitive motility mechanism, including the F-actin cytoskeleton, growth of invasive protrusions and the levels of signal molecules in human amniotic epithelial (FL) cells. Without extracellular EGF stimulation, the field stimulated a large growth of new protrusions, especially filopodia and lamellipodia, an increased population of vinculin-associated focal adhesions. And, an obvious reduction of stress fiber content in cell centers was found, corresponding to larger cell surface areas and decreased efficiency of actin assembly of FL cells in vitro, which was associated with a decrease in overall F-actin content and special distributions. These effects were also associated with changes in protein content or distribution patterns of the EGFR downstream motility-related signaling molecules. All of these effects are similar to those following epidermal growth factor (EGF) stimulation of the cells and are time dependent. These results suggest that power frequency MF exposure acutely affects the migration/motility-related actin cytoskeleton reorganization that is regulated by the EGFR-cytoskeleton signaling pathway. Therefore, upon the MF exposure, cells are likely altered to be ready to transfer into a state of migration in response to the stimuli. PMID:24505297

  13. Dynamic Control of Posture Across Locomotor Tasks

    PubMed Central

    Earhart, Gammon M.

    2013-01-01

    Successful locomotion depends on postural control to establish and maintain appropriate postural orientation of body segments relative to one another and to the environment, and to ensure dynamic stability of the moving body. This paper provides a framework for considering dynamic postural control, highlighting the importance of coordination, consistency, and challenges to postural control posed by various locomotor tasks such as turning and backward walking. The impacts of aging and various movement disorders on postural control are discussed broadly in an effort to provide a general overview of the field and recommendations for assessment of dynamic postural control across different populations in both clinical and research settings. Suggestions for future research on dynamic postural control during locomotion are also provided and include discussion of opportunities afforded by new and developing technologies, the need for long-term monitoring of locomotor performance in everyday activities, gaps in our knowledge of how targeted intervention approaches modify dynamic postural control, and the relative paucity of literature regarding dynamic postural control in movement disorder populations other than Parkinson disease. PMID:24132838

  14. Development of a spinal locomotor rheostat.

    PubMed

    Zhang, Hong-Yan; Issberner, Jon; Sillar, Keith T

    2011-07-12

    Locomotion in immature animals is often inflexible, but gradually acquires versatility to enable animals to maneuver efficiently through their environment. Locomotor activity in adults is produced by complex spinal cord networks that develop from simpler precursors. How does complexity and plasticity emerge during development to bestow flexibility upon motor behavior? And how does this complexity map onto the peripheral innervation fields of motorneurons during development? We show in postembryonic Xenopus laevis frog tadpoles that swim motorneurons initially form a homogenous pool discharging single action potential per swim cycle and innervating most of the dorsoventral extent of the swimming muscles. However, during early larval life, in the prelude to a free-swimming existence, the innervation fields of motorneurons become restricted to a more limited sector of each muscle block, with individual motorneurons reaching predominantly ventral, medial, or dorsal regions. Larval motorneurons then can also discharge multiple action potentials in each cycle of swimming and differentiate in terms of their firing reliability during swimming into relatively high-, medium-, or low-probability members. Many motorneurons fall silent during swimming but can be recruited with increasing locomotor frequency and intensity. Each region of the myotome is served by motorneurons spanning the full range of firing probabilities. This unfolding developmental plan, which occurs in the absence of movement, probably equips the organism with the neuronal substrate to bend, pitch, roll, and accelerate during swimming in ways that will be important for survival during the period of free-swimming larval life that ensues. PMID:21709216

  15. The GALS locomotor screen and disability.

    PubMed Central

    Plant, M J; Linton, S; Dodd, E; Jones, P W; Dawes, P T

    1993-01-01

    OBJECTIVES--Examination of the locomotor system is frequently neglected. Therefore, the GALS locomotor screen (Gait, Arms, Legs, Spine) has been proposed by Doherty et al as a practical method of identifying functionally important problems. This study was designed to test whether this screen reflects functional impairment, as measured by accepted health status measures. METHODS--Two observers performed the GALS screen in a total of 83 patients with a variety of musculoskeletal conditions. The examination components of GALS were rated by a simple 0 to 3 scale. Physical ability was further assessed by Health Activity Questionnaire (HAQ), Barthel index and Steinbrocker's ARA classification. RESULTS--For the total patient group, Spearman correlations between GALS and the three functional indices were good (r = 0.62 to 0.71, p < 0.001). Correlations were equally good for rheumatoid arthritis patients alone (r = 0.65 to 0.70, p < 0.001), but less good although still significant for the other miscellaneous rheumatic conditions (r = 0.31 to 0.46, p < 0.05). Observed proportional agreement between the two observers for the individual scores was > 70%, with a kappa statistic k = 0.49 to 0.74. CONCLUSIONS--The GALS screen is a reliable and valid measure of functional ability, compared with standard accepted indices in a variety of musculoskeletal diseases. This supports the proposal for its use as a screening test by general practitioners and medical students. PMID:8311541

  16. Long-Term Potentiation by Theta-Burst Stimulation Using Extracellular Field Potential Recordings in Acute Hippocampal Slices.

    PubMed

    Abrahamsson, Therese; Lalanne, Txomin; Watt, Alanna J; Sjöström, P Jesper

    2016-01-01

    This protocol describes how to carry out theta-burst long-term potentiation (LTP) with extracellular field recordings in acute rodent hippocampal slices. This method is relatively simple and noninvasive and provides a way to sample many neurons simultaneously, making it suitable for applications requiring higher throughput than whole-cell recording. PMID:27250947

  17. Effects of recombinant granulocyte colony-stimulating factor (rG-CSF) and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on acute radiation hematopoietic injury in mice

    SciTech Connect

    Tanikawa, S.; Nakao, I.; Tsuneoka, K.; Nara, N. )

    1989-09-01

    We have attempted to evaluate in vivo effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on acute radiation hematopoietic injury in mice. BDF1 mice, irradiated with 7.5-Gy x-rays, were injected i.p. twice daily for 10 days with 10(5) U recombinant human G-CSF, 3.75 x 10(5) U recombinant murine GM-CSF, or a combination of both. G-CSF significantly enhanced the recovery of not only peripheral leukocytes but also platelets and hematocrit on days 14 and 21 after irradiation. GM-CSF significantly enhanced the recovery of platelets on day 14 and peripheral leukocytes on day 21. G-CSF markedly enhanced the recovery of spleen colony-forming units (CFU-S), colony-forming units in culture (CFU-C), erythroid burst-forming units (BFU-E), and megakaryocyte colony-forming units (CFU-Meg) both in bone marrow and in the spleen. GM-CSF significantly enhanced the recovery of CFU-Meg in bone marrow on day 14. We found synergistic effects between G-CSF and GM-CSF on CFU-S, CFU-C, and CFU-Meg in the spleen on day 14, although we found antagonistic effects between G-CSF and GM-CSF on CFU-S and CFU-C in bone marrow on day 7, and on platelet counts on day 7. These results indicate that the administration of recombinant G-CSF and GM-CSF may be useful in accelerating hematopoietic recovery in patients with acute radiation hematopoietic injuries.

  18. Evidence for a Role of Orexin/Hypocretin System in Vestibular Lesion-Induced Locomotor Abnormalities in Rats

    PubMed Central

    Pan, Leilei; Qi, Ruirui; Wang, Junqin; Zhou, Wei; Liu, Jiluo; Cai, Yiling

    2016-01-01

    Vestibular damage can induce locomotor abnormalities in both animals and humans. Rodents with bilateral vestibular loss showed vestibular deficits syndrome such as circling, opisthotonus as well as locomotor and exploratory hyperactivity. Previous studies have investigated the changes in the dopamine system after vestibular loss, but the results are inconsistent and inconclusive. Numerous evidences indicate that the orexin system is implicated in central motor control. We hypothesized that orexin may be potentially involved in vestibular loss-induced motor disorders. In this study, we examined the effects of arsanilate- or 3,3′-iminodipropionitrile (IDPN)-induced vestibular lesion (AVL or IVL) on the orexin-A (OXA) labeling in rat hypothalamus using immunohistochemistry. The vestibular lesion-induced locomotor abnormalities were recorded and verified using a histamine H4 receptor antagonist JNJ7777120 (20 mg/kg, i.p.). The effects of the orexin receptor type 1 antagonist SB334867 (16 μg, i.c.v.) on these behavior responses were also investigated. At 72 h post-AVL and IVL, animals exhibited vestibular deficit syndrome and locomotor hyperactivity in the home cages. These responses were significantly alleviated by JNJ7777120 which also eliminated AVL-induced increases in exploratory behavior in an open field. The numbers of OXA-labeled neurons in the hypothalamus were significantly increased in the AVL animals at 72 h post-AVL and in the IVL animals at 24, 48, and 72 h post-IVL. SB334867 significantly attenuated the vestibular deficit syndrome and locomotor hyperactivity at 72 h post-AVL and IVL. It also decreased exploratory behavior in the AVL animals. These results suggested that the alteration of OXA expression might contribute to locomotor abnormalities after acute vestibular lesion. The orexin receptors might be the potential therapeutic targets for vestibular disorders. PMID:27507932

  19. Evidence for a Role of Orexin/Hypocretin System in Vestibular Lesion-Induced Locomotor Abnormalities in Rats.

    PubMed

    Pan, Leilei; Qi, Ruirui; Wang, Junqin; Zhou, Wei; Liu, Jiluo; Cai, Yiling

    2016-01-01

    Vestibular damage can induce locomotor abnormalities in both animals and humans. Rodents with bilateral vestibular loss showed vestibular deficits syndrome such as circling, opisthotonus as well as locomotor and exploratory hyperactivity. Previous studies have investigated the changes in the dopamine system after vestibular loss, but the results are inconsistent and inconclusive. Numerous evidences indicate that the orexin system is implicated in central motor control. We hypothesized that orexin may be potentially involved in vestibular loss-induced motor disorders. In this study, we examined the effects of arsanilate- or 3,3'-iminodipropionitrile (IDPN)-induced vestibular lesion (AVL or IVL) on the orexin-A (OXA) labeling in rat hypothalamus using immunohistochemistry. The vestibular lesion-induced locomotor abnormalities were recorded and verified using a histamine H4 receptor antagonist JNJ7777120 (20 mg/kg, i.p.). The effects of the orexin receptor type 1 antagonist SB334867 (16 μg, i.c.v.) on these behavior responses were also investigated. At 72 h post-AVL and IVL, animals exhibited vestibular deficit syndrome and locomotor hyperactivity in the home cages. These responses were significantly alleviated by JNJ7777120 which also eliminated AVL-induced increases in exploratory behavior in an open field. The numbers of OXA-labeled neurons in the hypothalamus were significantly increased in the AVL animals at 72 h post-AVL and in the IVL animals at 24, 48, and 72 h post-IVL. SB334867 significantly attenuated the vestibular deficit syndrome and locomotor hyperactivity at 72 h post-AVL and IVL. It also decreased exploratory behavior in the AVL animals. These results suggested that the alteration of OXA expression might contribute to locomotor abnormalities after acute vestibular lesion. The orexin receptors might be the potential therapeutic targets for vestibular disorders. PMID:27507932

  20. Quantitative Trait Loci for Locomotor Behavior in Drosophila melanogaster

    PubMed Central

    Jordan, Katherine W.; Morgan, Theodore J.; Mackay, Trudy F. C.

    2006-01-01

    Locomotion is an integral component of most animal behaviors and many human diseases and disorders are associated with locomotor deficits, but little is known about the genetic basis of natural variation in locomotor behavior. Locomotion is a complex trait, with variation attributable to the joint segregation of multiple interacting quantitative trait loci (QTL), with effects that are sensitive to the environment. We assessed variation in a component of locomotor behavior (locomotor reactivity) in a population of 98 recombinant inbred lines of Drosophila melanogaster and mapped four QTL affecting locomotor reactivity by linkage to polymorphic roo transposable element insertion sites. We used complementation tests of deficiencies to fine map these QTL to 12 chromosomal regions and complementation tests of mutations to identify 13 positional candidate genes affecting locomotor reactivity, including Dopa decarboxylase (Ddc), which catalyzes the final step in the synthesis of serotonin and dopamine. Linkage disequilibrium mapping in a population of 164 second chromosome substitution lines derived from a single natural population showed that polymorphisms at Ddc were associated with naturally occurring genetic variation in locomotor behavior. These data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in locomotor reactivity. PMID:16783013

  1. Locomotor Behaviour of Blattella germanica Modified by DEET

    PubMed Central

    Sfara, Valeria; Mougabure-Cueto, Gastón A.; Zerba, Eduardo N.; Alzogaray, Raúl A.

    2013-01-01

    N,N-diethyl-3-methylbenzamide (DEET) is the active principle of most insect repellents used worldwide. However, its toxicity on insects has not been widely studied. The aim of this work is to study the effects of DEET on the locomotor activity of Blattella germanica. DEET has a dose-dependent repellent activity on B. germanica. Locomotor activity was significantly lower when insects were pre-exposed to 700 µg/cm2 of DEET for 20 or 30 minutes, but it did not change when pre-exposure was shorter. Locomotor activity of insects that were pre-exposed to 2.000 µg/cm2 of DEET for 10 minutes was significantly lower than the movement registered in controls. No differences were observed when insects were pre-exposed to lower concentrations of DEET. A 30-minute pre-exposure to 700 µg/cm2 of DEET caused a significant decrease in locomotor activity. Movement was totally recovered 24 h later. The locomotor activity measured during the exposure to different concentrations of DEET remained unchanged. Insects with decreased locomotor activity were repelled to the same extent than control insects by the same concentration of DEET. We demonstrated that the repellency and modification of locomotor activity elicited by DEET are non-associated phenomena. We also suggested that the reduction in locomotor activity indicates toxicity of DEET, probably to insect nervous system. PMID:24376701

  2. Locomotor behaviour of Blattella germanica modified by DEET.

    PubMed

    Sfara, Valeria; Mougabure-Cueto, Gastón A; Zerba, Eduardo N; Alzogaray, Raúl A

    2013-01-01

    N,N-diethyl-3-methylbenzamide (DEET) is the active principle of most insect repellents used worldwide. However, its toxicity on insects has not been widely studied. The aim of this work is to study the effects of DEET on the locomotor activity of Blattella germanica. DEET has a dose-dependent repellent activity on B. germanica. Locomotor activity was significantly lower when insects were pre-exposed to 700 µg/cm(2) of DEET for 20 or 30 minutes, but it did not change when pre-exposure was shorter. Locomotor activity of insects that were pre-exposed to 2.000 µg/cm(2) of DEET for 10 minutes was significantly lower than the movement registered in controls. No differences were observed when insects were pre-exposed to lower concentrations of DEET. A 30-minute pre-exposure to 700 µg/cm(2) of DEET caused a significant decrease in locomotor activity. Movement was totally recovered 24 h later. The locomotor activity measured during the exposure to different concentrations of DEET remained unchanged. Insects with decreased locomotor activity were repelled to the same extent than control insects by the same concentration of DEET. We demonstrated that the repellency and modification of locomotor activity elicited by DEET are non-associated phenomena. We also suggested that the reduction in locomotor activity indicates toxicity of DEET, probably to insect nervous system. PMID:24376701

  3. Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury

    PubMed Central

    Smith, Andrew C.; Mummidisetty, Chaithanya K.

    2015-01-01

    Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs. PMID:25609110

  4. The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

    SciTech Connect

    Moroni, Maria; Ngudiankama, Barbara F.; Christensen, Christine; Olsen, Cara H.; Owens, Rossitsa; Lombardini, Eric D.; Holt, Rebecca K.; Whitnall, Mark H.

    2013-08-01

    Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes.

  5. A Pilot Study of Stimulant Medication for Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) Who Are Parents of Adolescents with ADHD: The Acute Effects of Stimulant Medication on Observed Parent–Adolescent Interactions

    PubMed Central

    Waxmonsky, James G.; Waschbusch, Daniel A.; Humphrey, Hugh; Alfonso, Alexandra; Crum, Kathleen I.; Bernstein, Melissa; Slavec, Janine; Augustus, Junea N.; Pelham, William E.

    2014-01-01

    Abstract Objective: This study explores the use of stimulant medication for parents with attention-deficit/hyperactivity disorder (ADHD) who also have adolescents with ADHD. Methods: Five parents, diagnosed with ADHD, had their dose of lisdexamfetamine (LDX) titrated to optimal effect. Next, parents and their adolescents completed two interactions, once when parents were on placebo and once when parents were on optimal dose of LDX, to assess acute effects of parental medication on parenting during a neutral discussion (NeuDiss), a problem discussion (ProbDiss), and a homework task (HW). Results: Parents demonstrated a significant decrease in the ratio of commands to total verbalizations during the NeuDiss on LDX compared with placebo. Although no other statistically significant effects emerged at the p<0.05 level, moderate to large effects of medication on some aspects of parenting related to the amount and timing of speech (i.e., total verbalizations, total commands, ratio of commands to total verbalizations, and responsiveness) emerged and varied by task. Parental stimulant medication did not appear to impact the content of parents' speech (i.e., use of negative talk or praise). Conclusions: These results add to a growing literature suggesting that treatment for parental ADHD may impact parenting performance, and suggest that attention to parental ADHD in treatment for adolescents with ADHD may possibly enhance family functioning. PMID:25386742

  6. The mesencephalic locomotor region sends a bilateral glutamatergic drive to hindbrain reticulospinal neurons in a tetrapod.

    PubMed

    Ryczko, Dimitri; Auclair, Francois; Cabelguen, Jean-Marie; Dubuc, Réjean

    2016-05-01

    In vertebrates, stimulation of the mesencephalic locomotor region (MLR) on one side evokes symmetrical locomotor movements on both sides. How this occurs was previously examined in detail in a swimmer using body undulations (lamprey), but in tetrapods the downstream projections from the MLR to brainstem neurons are not fully understood. Here we examined the brainstem circuits from the MLR to identified reticulospinal neurons in the salamander Notophthalmus viridescens. Using neural tracing, we show that the MLR sends bilateral projections to the middle reticular nucleus (mRN, rostral hindbrain) and the inferior reticular nucleus (iRN, caudal hindbrain). Ca(2+) imaging coupled to electrophysiology in in vitro isolated brains revealed very similar responses in reticulospinal neurons on both sides to a unilateral MLR stimulation. As the strength of MLR stimulation was increased, the responses increased in size in reticulospinal neurons of the mRN and iRN, but the responses in the iRN were smaller. Bath-application or local microinjections of glutamatergic antagonists markedly reduced reticulospinal neuron responses, indicating that the MLR sends glutamatergic inputs to reticulospinal neurons. In addition, reticulospinal cells responded to glutamate microinjections and the size of the responses paralleled the amount of glutamate microinjected. Immunofluorescence coupled with anatomical tracing confirmed the presence of glutamatergic projections from the MLR to reticulospinal neurons. Overall, we show that the brainstem circuits activated by the MLR in the salamander are organized similarly to those previously described in lampreys, indicating that the anatomo-physiological features of the locomotor drive are well conserved in vertebrates. J. Comp. Neurol. 524:1361-1383, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26470600

  7. Antidepressant-like activity of EMD 386088, a 5-HT6 receptor partial agonist, following systemic acute and chronic administration to rats.

    PubMed

    Jastrzębska-Więsek, Magdalena; Siwek, Agata; Partyka, Anna; Szewczyk, Bernadeta; Sowa-Kućma, Magdalena; Wasik, Anna; Kołaczkowski, Marcin; Wesołowska, Anna

    2015-10-01

    The study was designed to examine the potency of EMD 386088, a 5-HT6 receptor partial agonist, to exert antidepressant-like properties in animal models following acute and chronic intraperitoneal administration to rats. The modified rat forced swim test (FST) was utilized to examine a potential antidepressant effect of EMD 386088 after acute treatment (30 min before the test) and three times in a 24-h administration scheme (24 h, 5 h, and 30 min prior to the FST). The olfactory bulbectomy (OB) model was used to assess its antidepressant-like properties after chronic treatment (the drug was administered once daily for 14 days). EMD 386088 showed an antidepressant-like effect in all conducted tests. Its activity in FST after its acute administration (5 mg/kg) was blocked by the selective 5-HT6 receptor antagonist SB 271046. The obtained results seem to be specific, as there was no observed locomotor stimulation by the drug given at a lower/antidepressant dose. In the three times in the 24-h treatment scheme, EMD 386088 (2.5 mg/kg) exerted antidepressant properties in FST as well as increased locomotor activity in the open field test. Chronic administration of EMD 386088 (2.5 mg/kg) significantly improved the learning deficit in OB rats without affecting performance in Sham-operated (SH) animals in the passive avoidance test, and reduced OB-related rats' locomotor hyperactivity, but did not change the number of rearing + peeping episodes. The obtained findings suggest that EMD 386088 produces antidepressant-like activity after systemic acute and chronic administration which may result from direct stimulation of 5-HT6 receptors. PMID:26077660

  8. Effects of Nicotine on Ethanol-Induced Locomotor Sensitization: A Model of Neuroadaptation

    PubMed Central

    Gubner, Noah R.; Phillips, Tamara J.

    2015-01-01

    Co-morbid use of nicotine-containing tobacco products and alcohol (ethanol) is prevalent in young adults initiating use and in alcohol dependent adults, suggesting that these drugs in combination may increase risk to develop dependence on one or both drugs. Neuroadaptations caused by repeated drug exposure are related to the development of drug dependence and vulnerability to relapse. Locomotor sensitization has been used as a behavioral measure used to detect changes in neural drug sensitivity that are thought to contribute to drug dependence and relapse. Locomotor sensitization was measured in the current studies to examine potential differences in the effects of nicotine and ethanol given alone and in combination. Baseline activity levels of DBA/2J mice were assessed on 2 days, then mice were treated for ten days with saline, nicotine (1 or 2 mg/kg of nicotine tartrate), ethanol (1 or 2 g/kg), or nicotine plus ethanol and locomotor activity was assessed every third day. On the following day, all mice were challenged with ethanol to measure the expression of sensitization. Mice treated with both nicotine and ethanol exhibited greater stimulation than predicted from the combined independent effects of these drugs, consistent with our previously published results. The combined effects of nicotine and ethanol on locomotor sensitization were dependent on the dose of ethanol and whether testing was performed after the drugs were given together, or after challenge with ethanol alone. These results suggest that nicotine and ethanol in combination can have neuroadaptive effects that differ from the independent effects of these drugs. PMID:25857831

  9. Plantar tactile perturbations enhance transfer of split-belt locomotor adaptation.

    PubMed

    Mukherjee, Mukul; Eikema, Diderik Jan A; Chien, Jung Hung; Myers, Sara A; Scott-Pandorf, Melissa; Bloomberg, Jacob J; Stergiou, Nicholas

    2015-10-01

    Patterns of human locomotion are highly adaptive and flexible and depend on the environmental context. Locomotor adaptation requires the use of multisensory information to perceive altered environmental dynamics and generate an appropriate movement pattern. In this study, we investigated the use of multisensory information during locomotor learning. Proprioceptive perturbations were induced by vibrating tactors, placed bilaterally over the plantar surfaces. Under these altered sensory conditions, participants were asked to perform a split-belt locomotor task representative of motor learning. Twenty healthy young participants were separated into two groups: no-tactors (NT) and tactors (TC). All participants performed an overground walking trial, followed by treadmill walking including 18 min of split-belt adaptation and an overground trial to determine transfer effects. Interlimb coordination was quantified by symmetry indices and analyzed using mixed repeated-measures ANOVAs. Both groups adapted to the locomotor task, indicated by significant reductions in gait symmetry during the split-belt task. No significant group differences in spatiotemporal and kinetic parameters were observed on the treadmill. However, significant group differences were observed overground. Step and swing time asymmetries learned on the split-belt treadmill were retained and decayed more slowly overground in the TC group whereas in NT, asymmetries were rapidly lost. These results suggest that tactile stimulation contributed to increased lower limb proprioceptive gain. High proprioceptive gain allows for more persistent overground after effects, at the cost of reduced adaptability. Such persistence may be utilized in populations displaying pathologic asymmetric gait by retraining a more symmetric pattern. PMID:26169104

  10. Effects of nicotine on ethanol-induced locomotor sensitization: A model of neuroadaptation.

    PubMed

    Gubner, Noah R; Phillips, Tamara J

    2015-07-15

    Co-morbid use of nicotine-containing tobacco products and alcohol (ethanol) is prevalent in young adults initiating use and in alcohol dependent adults, suggesting that these drugs in combination may increase risk to develop dependence on one or both drugs. Neuroadaptations caused by repeated drug exposure are related to the development of drug dependence and vulnerability to relapse. Locomotor sensitization has been used as a behavioral measure used to detect changes in neural drug sensitivity that are thought to contribute to drug dependence and relapse. Locomotor sensitization was measured in the current studies to examine potential differences in the effects of nicotine and ethanol given alone and in combination. Baseline activity levels of DBA/2J mice were assessed on 2 days, then mice were treated for 10 days with saline, nicotine (1 or 2mg/kg of nicotine tartrate), ethanol (1 or 2g/kg), or nicotine plus ethanol and locomotor activity was assessed every third day. On the following day, all mice were challenged with ethanol to measure the expression of sensitization. Mice treated with both nicotine and ethanol exhibited greater stimulation than predicted from the combined independent effects of these drugs, consistent with our previously published results. The combined effects of nicotine and ethanol on locomotor sensitization were dependent on the dose of ethanol and whether testing was performed after the drugs were given together, or after challenge with ethanol alone. These results suggest that nicotine and ethanol in combination can have neuroadaptive effects that differ from the independent effects of these drugs. PMID:25857831

  11. The effects of acute exposure to ethanol on neurotensin and guanine nucleotide-stimulation of phospholipase C activity in intact NIE-115 neuroblastoma cells

    SciTech Connect

    Smith, T.L. )

    1990-01-01

    Both ethanol and neurotensin produce sedation and hypothermia. When administered in combination the behavioral effects of these two substances are potentiated. In order to better understand the biochemical nature of this interaction, the direct effects of ethanol on neurotensin receptors and an associated signal transduction process were determined in NIE-115 neuroblastoma cells. Ethanol in physiologically relevant concentrations significantly reduced neurotensin stimulated ({sup 3}H)inositol phosphate production while having no effect on the specific binding of ({sup 3}H)neurotensin. In addition, ethanol up to 200 mM had no effect on GTPYS mediated ({sup 3}H)inositol phosphate production. The results indicate that acute exposure ethanol partially disrupts the normal coupling of activated neurotensin receptors to the guanine nucleotide binding protein associated with phospholipase C.

  12. Integrated Locomotor Function Tests for Countermeasure Evaluation

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Landsness, E. C.; Black, F. O.

    2005-01-01

    Following spaceflight crewmembers experience locomotor dysfunction due to inflight adaptive alterations in sensorimotor function. Countermeasures designed to mitigate these postflight gait alterations need to be assessed with a new generation of tests that evaluate the interaction of various sensorimotor sub-systems central to locomotor control. The goal of the present study was to develop new functional tests of locomotor control that could be used to test the efficacy of countermeasures. These tests were designed to simultaneously examine the function of multiple sensorimotor systems underlying the control of locomotion and be operationally relevant to the astronaut population. Traditionally, gaze stabilization has been studied almost exclusively in seated subjects performing target acquisition tasks requiring only the involvement of coordinated eye-head movements. However, activities like walking involve full-body movement and require coordination between lower limbs and the eye-head-trunk complex to achieve stabilized gaze during locomotion. Therefore the first goal of this study was to determine how the multiple, interdependent, full-body sensorimotor gaze stabilization subsystems are functionally coordinated during locomotion. In an earlier study we investigated how alteration in gaze tasking changes full-body locomotor control strategies. Subjects walked on a treadmill and either focused on a central point target or read numeral characters. We measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. In comparison to the point target fixation condition, the results of the number reading task showed that compensatory head pitch movements increased, peak head acceleration was reduced and knee flexion at heel-strike was increased. In a more recent study we investigated the

  13. Neurophysiological responses to unpleasant stimuli (acute electrical stimulations and emotional pictures) are increased in patients with schizophrenia.

    PubMed

    Duval, Céline Z; Goumon, Yannick; Kemmel, Véronique; Kornmeier, Jürgen; Dufour, André; Andlauer, Olivier; Vidailhet, Pierre; Poisbeau, Pierrick; Salvat, Eric; Muller, André; Mensah-Nyagan, Ayikoé G; Schmidt-Mutter, Catherine; Giersch, Anne

    2016-01-01

    Patients with schizophrenia have often been described as insensitive to nociceptive signals, but objective evidence is sparse. We address this question by combining subjective behavioral and objective neurochemical and neurophysiological measures. The present study involved 21 stabilized and mildly symptomatic patients with schizophrenia and 21 control subjects. We applied electrical stimulations below the pain threshold and assessed sensations of pain and unpleasantness with rating scales, and Somatosensory Evoked Potentials (SEPs/EEG). We also measured attention, two neurochemical stress indices (ACTH/cortisol), and subjective VEPs/EEG responses to visual emotional stimuli. Our results revealed that, subjectively, patients' evaluations do not differ from controls. However, the amplitude of EEG evoked potentials was greater in patients than controls as early as 50 ms after electrical stimulations and beyond one second after visual processing of emotional pictures. Such responses could not be linked to the stress induced by the stimulations, since stress hormone levels were stable. Nor was there a difference between patients and controls in respect of attention performance and tactile sensitivity. Taken together, all indices measured in patients in our study were either heightened or equivalent relative to healthy volunteers. PMID:26935652

  14. Neurophysiological responses to unpleasant stimuli (acute electrical stimulations and emotional pictures) are increased in patients with schizophrenia

    PubMed Central

    Duval, Céline Z.; Goumon, Yannick; Kemmel, Véronique; Kornmeier, Jürgen; Dufour, André; Andlauer, Olivier; Vidailhet, Pierre; Poisbeau, Pierrick; Salvat, Eric; Muller, André; Mensah-Nyagan, Ayikoé G.; Schmidt-Mutter, Catherine; Giersch, Anne

    2016-01-01

    Patients with schizophrenia have often been described as insensitive to nociceptive signals, but objective evidence is sparse. We address this question by combining subjective behavioral and objective neurochemical and neurophysiological measures. The present study involved 21 stabilized and mildly symptomatic patients with schizophrenia and 21 control subjects. We applied electrical stimulations below the pain threshold and assessed sensations of pain and unpleasantness with rating scales, and Somatosensory Evoked Potentials (SEPs/EEG). We also measured attention, two neurochemical stress indices (ACTH/cortisol), and subjective VEPs/EEG responses to visual emotional stimuli. Our results revealed that, subjectively, patients’ evaluations do not differ from controls. However, the amplitude of EEG evoked potentials was greater in patients than controls as early as 50 ms after electrical stimulations and beyond one second after visual processing of emotional pictures. Such responses could not be linked to the stress induced by the stimulations, since stress hormone levels were stable. Nor was there a difference between patients and controls in respect of attention performance and tactile sensitivity. Taken together, all indices measured in patients in our study were either heightened or equivalent relative to healthy volunteers. PMID:26935652

  15. Functional redundancy of ventral spinal locomotor pathways.

    PubMed

    Loy, David N; Magnuson, David S K; Zhang, Y Ping; Onifer, Stephen M; Mills, Michael D; Cao, Qi-lin; Darnall, Jessica B; Fajardo, Lily C; Burke, Darlene A; Whittemore, Scott R

    2002-01-01

    Identification of long tracts responsible for the initiation of spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. Pathways derived from the mesencephalic locomotor region and pontomedullary medial reticular formation responsible for fictive locomotion in decerebrate preparations project to the thoracolumbar levels of the spinal cord via reticulospinal axons in the ventrolateral funiculus (VLF). However, white matter regions critical for spontaneous over-ground locomotion remain unclear because cats, monkeys, and humans display varying degrees of locomotor recovery after ventral SCIs. We studied the contributions of myelinated tracts in the VLF and ventral columns (VC) to spontaneous over-ground locomotion in the adult rat using demyelinating lesions. Animals received ethidium bromide plus photon irradiation producing discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, VC, VLF-VC, or complete ventral white matter (CV). Behavior [open-field Basso, Beattie, and Bresnahan (BBB) scores and grid walking] and transcranial magnetic motor-evoked potentials (tcMMEP) were studied at 1, 2, and 4 weeks after lesion. VLF lesions resulted in complete loss or severe attenuation of tcMMEPs, with mean BBB scores of 18.0, and no grid walking deficits. VC lesions produced behavior similar to VLF-lesioned animals but did not significantly affect tcMMEPs. VC-VLF and CV lesions resulted in complete loss of tcMMEP signals with mean BBB scores of 12.7 and 6.5, respectively. Our data support a diffuse arrangement of axons within the ventral white matter that may comprise a system of multiple descending pathways subserving spontaneous over-ground locomotion in the intact animal. PMID:11756515

  16. The Anti-(+)-Methamphetamine Monoclonal Antibody mAb7F9 Attenuates Acute (+)-Methamphetamine Effects on Intracranial Self-Stimulation in Rats

    PubMed Central

    Harris, Andrew C.; LeSage, Mark G.; Shelley, David; Perry, Jennifer L.; Pentel, Paul R.; Owens, S. Michael

    2015-01-01

    Passive immunization with monoclonal antibodies (mAbs) against (+)-methamphetamine (METH) is being evaluated for the treatment of METH addiction. A human/mouse chimeric form of the murine anti-METH mAb7F9 has entered clinical trials. This study examined the effects of murine mAb7F9 on certain addiction-related behavioral effects of METH in rats as measured using intracranial self-stimulation (ICSS). Initial studies indicated that acute METH (0.1-0.56 mg/kg, s.c.) lowered the minimal (threshold) stimulation intensity that maintained ICSS. METH (0.3 mg/kg, s.c.) also blocked elevations in ICSS thresholds (anhedonia-like behavior) during spontaneous withdrawal from a chronic METH infusion (10 mg/kg/day x 7 days). In studies examining effects of i.v. pretreatment with mAb7F9 (at 30, 100, or 200 mg/kg), 200 mg/kg blocked the ability of an initial injection of METH (0.3 mg/kg, s.c.) to reduce baseline ICSS thresholds, but was less capable of attenuating the effect of subsequent daily injections of METH. MAb7F9 (200 mg/kg) also produced a small but significant reduction in the ability of METH (0.3 mg/kg, s.c.) to reverse METH withdrawal-induced elevations in ICSS thresholds. These studies demonstrate that mAb7F9 can partially attenuate some addiction-related effects of acute METH in an ICSS model, and provide some support for the therapeutic potential of mAb7F9 for the treatment of METH addiction. PMID:25742165

  17. Home tank water versus novel water differentially affect alcohol-induced locomotor activity and anxiety related behaviours in zebrafish.

    PubMed

    Tran, Steven; Facciol, Amanda; Gerlai, Robert

    2016-05-01

    The zebrafish may be uniquely well suited for studying alcohol's mechanisms of action in vivo, since alcohol can be administered via immersion in a non-invasive manner. Despite the robust behavioural effects of alcohol administration in mammals, studies reporting the locomotor stimulant and anxiolytic effects of alcohol in zebrafish have been inconsistent. In the current study, we examined whether differences in the type of water used for alcohol exposure and behavioural testing contribute to these inconsistencies. To answer this question, we exposed zebrafish to either home water from their housing tanks or novel water from an isolated reservoir (i.e. water lacking zebrafish chemosensory and olfactory cues) with 0% or 1% v/v alcohol for 30min, a 2×2 between subject experimental designs. Behavioural responses were quantified throughout the 30-minute exposure session via a video tracking system. Although control zebrafish exposed to home water and novel water were virtually indistinguishable in their behavioural responses, alcohol's effect on locomotor activity and anxiety-like behavioural responses were dependent on the type of water used for testing. Alcohol exposure in home tank water produced a mild anxiolytic and locomotor stimulant effect, whereas alcohol exposure in novel water produced an anxiogenic effect without altering locomotor activity. These results represent a dissociation between alcohol's effects on locomotor and anxiety related responses, and also illustrate how environmental factors, in this case familiarity with the water, may interact with such effects. In light of these findings, we urge researchers to explicitly state the type of water used. PMID:26921455

  18. Acute effects of morphine and opioid peptides on the motility and responses of rat colon to electrical stimulation.

    PubMed Central

    Gillan, M. G.; Pollock, D.

    1980-01-01

    1 Morphine and leucine- and methionine-enkephalins inhibited the contractile response of the pithed rat colon to electrical stimulation of the spinal motor outflows and inhibited motor responses of the isolated colon to field stimulation. 2 Morphine and the opioid peptides also had an excitatory action in the colon. In the pithed rat, opiates caused regular fluctuations in intracolonic pressure and in the isolated colon, caused regular waves of contraction. This excitatory response was produced by low concentrations of the enkephalins (2 X 10(-8) M, 2 X 10(-9) M), was stereospecific and was antagonized by naloxone. 3 Opiate-induced contractions in the isolated colon were inhibited by catecholamines, adenine nucleotides and by phosphodiesterase inhibitors. These contractions were unaffected by ergotamine and tolazoline, or by propranolol. 4 The excitatory action of opiates in the isolated colon was not antagonized and usually was potentiated by atropine, (+)-tubocurarine and hexamethonium. In the absence of opiates, these drugs also produced similar waves of contraction, which were unaffected by naloxone. 5 Opiate-induced contractions occurred in colon rendered unresponsive to 5-hydroxytryptamine (5-HT) and these contractions were potentiated by the 5-HT antagonist, lysergic acid diethylamide, which, when administered alone, caused similar contractions. The 5-HT antagonist, cyproheptadine, inhibited opiate-induced contractions but was non-specific, since it also inhibited responses of the colon to carbachol and KC1. 6 Opiate-induced contractions were unaffected by procaine and were potentiated by tetrodotoxin. Both of these drugs, when administered alone, produced waves of contractions, which were similar to those produced by opiates but were unaffected by naloxone. 7 Contractions produced in the isolated colon either by opiates, atropine or (+)-tubocurarine, or any combination of these drugs, were inhibited by field stimulation applied at the peak of a wave of

  19. Low and high cocaine locomotor responding male Sprague-Dawley rats differ in rapid cocaine-induced regulation of striatal dopamine transporter function.

    PubMed

    Mandt, Bruce H; Zahniser, Nancy R

    2010-03-01

    Adult outbred Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively). Importantly, LCRs and HCRs are distinguished by their differential responsiveness to acute cocaine-induced (but not baseline) locomotor activity, inhibition of the dopamine transporter (DAT) and resulting extracellular DA (HCR > LCR), as well as by repeated cocaine-induced locomotor sensitization and measures of cocaine's rewarding and reinforcing effects (LCR > HCR). Curiously, 30 min after acute cocaine HCRs exhibit greater DAT-mediated [(3)H]DA uptake into striatal synaptosomes than LCRs. To investigate this finding further, we measured locomotor activity, striatal [(3)H]DA uptake kinetics and DAT cell surface expression in LCRs and HCRs over an extended period (25-180 min) after a single relatively low-dose of cocaine (10 mg/kg, i.p.). HCRs exhibited the "predicted" locomotor response: a marked initial activation that returned to baseline by 120 min post-injection. While LCRs exhibited a >50% lower maximal locomotor response, this increase was sustained, lasting approximately 33% longer than in HCRs. At 25 min post-cocaine, maximal velocity (V(max)) of [(3)H]DA uptake was significantly higher by 25% in HCRs than LCRs, with no difference in affinity (K(m)). Despite the DAT V(max) difference, however, DAT surface expression did not differ between LCRs and HCRs. There was a similar trend (HCR > LCR) for DAT V(max) at 40 min, but not at 150 or 180 min. These findings suggest that, compared to LCRs, HCRs have an enhanced ability to rapidly up-regulate DAT function in response to acute cocaine, which may contribute to their more "normal" cocaine-induced locomotor activation. PMID:19951714

  20. A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice.

    PubMed

    Long, Leonora E; Chesworth, Rose; Huang, Xu-Feng; McGregor, Iain S; Arnold, Jonathon C; Karl, Tim

    2010-08-01

    Cannabis contains over 70 unique compounds and its abuse is linked to an increased risk of developing schizophrenia. The behavioural profiles of the psychotropic cannabis constituent Delta9-tetrahydrocannabinol (Delta9-THC) and the non-psychotomimetic constituent cannabidiol (CBD) were investigated with a battery of behavioural tests relevant to anxiety and positive, negative and cognitive symptoms of schizophrenia. Male adult C57BL/6JArc mice were given 21 daily intraperitoneal injections of vehicle, Delta9-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). Delta9-THC produced the classic cannabinoid CB1 receptor-mediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects. While sedative at this dose, Delta9-THC (10 mg/kg) produced locomotor-independent anxiogenic effects in the open-field and light-dark tests. Chronic CBD produced moderate anxiolytic-like effects in the open-field test at 50 mg/kg and in the light-dark test at a low dose (1 mg/kg). Acute and chronic Delta9-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with Delta9-THC (0.3, 3 and 10 mg/kg) or CBD (1, 5 and 50 mg/kg) and by chronic CBD (1 mg/kg). Chronic CBD (50 mg/kg) attenuated dexamphetamine (5 mg/kg)-induced hyperlocomotion, suggesting an antipsychotic-like action for this cannabinoid. Chronic Delta9-THC decreased locomotor activity before and after dexamphetamine administration suggesting functional antagonism of the locomotor stimulant effect. These data provide the first evidence of anxiolytic- and antipsychotic-like effects of chronic but not acute CBD in C57BL/6JArc mice, extending findings from acute studies in other inbred mouse strains and rats. PMID:19785914

  1. Acute running stimulates hippocampal dopaminergic neurotransmission in rats, but has no influence on brain-derived neurotrophic factor

    PubMed Central

    Goekint, Maaike; Bos, Inge; Heyman, Elsa; Michotte, Yvette; Sarre, Sophie

    2012-01-01

    Hippocampal brain-derived neurotrophic factor (BDNF) protein is increased with exercise in rats. Monoamines seem to play a role in the regulation of BDNF, and monoamine neurotransmission is known to increase with exercise. The purpose of this study was to examine the influence of acute exercise on monoaminergic neurotransmission and BDNF protein concentrations. Hippocampal microdialysis was performed in rats that were subjected to 60 min of treadmill running at 20 m/min or rest. Two hours postexercise, the rats were killed, and the hippocampus was dissected. In experiments without microdialysis, hippocampus and serum samples were collected immediately after exercise. Exercise induced a twofold increase in hippocampal dopamine release. Noradrenaline and serotonin release were not affected. Hippocampal BDNF levels were not influenced, whether they were measured immediately or 2 h after the exercise protocol. Serum BDNF levels did not change either, but serum BDNF was negatively correlated to peripheral corticosterone concentrations, indicating a possible inhibitory reaction to the stress of running. Sixty minutes of exercise enhances dopamine release in the hippocampus of the rat in vivo. However, this increase is not associated with changes in BDNF protein levels immediately nor 2 h after the acute exercise bout. An increased corticosterone level might be the contributing factor for the absence of changes in BDNF. PMID:22134693

  2. Expression profiling of skeletal muscle following acute and chronic β2-adrenergic stimulation: implications for hypertrophy, metabolism and circadian rhythm

    PubMed Central

    Pearen, Michael A; Ryall, James G; Lynch, Gordon S; Muscat, George EO

    2009-01-01

    Background Systemic administration of β-adrenoceptor (β-AR) agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context of energy homeostasis, the importance of β-AR signaling has been highlighted by the inability of β1-3-AR-deficient mice to regulate energy expenditure and susceptibility to diet induced obesity. However, the molecular pathways and gene expression changes that initiate and maintain these phenotypic modulations are poorly understood. Therefore, the aim of this study was to identify differential changes in gene expression in murine skeletal muscle associated with systemic (acute and chronic) administration of the β2-AR agonist formoterol. Results Skeletal muscle gene expression (from murine tibialis anterior) was profiled at both 1 and 4 hours following systemic administration of the β2-AR agonist formoterol, using Illumina 46K mouse BeadArrays. Illumina expression profiling revealed significant expression changes in genes associated with skeletal muscle hypertrophy, myoblast differentiation, metabolism, circadian rhythm, transcription, histones, and oxidative stress. Differentially expressed genes relevant to the regulation of muscle mass and metabolism (in the context of the hypertrophic phenotype) were further validated by quantitative RT-PCR to examine gene expression in response to both acute (1-24 h) and chronic administration (1-28 days) of formoterol at multiple timepoints. In terms of skeletal muscle hypertrophy, attenuation of myostatin signaling (including differential expression of myostatin, activin receptor IIB, phospho-Smad3 etc) was observed following acute and chronic administration of formoterol. Acute (but not chronic) administration of formoterol also significantly induced the expression of genes involved in oxidative metabolism, including hexokinase 2, sorbin and SH3 domain containing 1, and uncoupling protein 3. Interestingly, formoterol administration also appeared to

  3. Alterations in locomotor activity after microinjections of GBR-12909, selective dopamine antagonists or neurotensin into the medial prefrontal cortex.

    PubMed

    Radcliffe, R A; Erwin, V G

    1996-06-01

    It has been postulated that increased dopamine (DA) activity in the medial prefrontal cortex (mPFC) exerts an inhibitory influence over DA release in the nucleus accumbens and, thus, also over locomotor activity. Experiments were designed to examine the role of mPFC DA and neurotensin (NT), a neuropeptide which interacts with DA, in spontaneous locomotor activity. LS/IBG mice were injected bilaterally with either GBR-12909, a selective DA uptake blocker, the DA D1 receptor antagonist R-(+)-SCH-23390, the DA D2 receptor antagonist epidepride, NT or a combination of drugs. GBR-12909 produced a U-shaped dose-response curve with a maximum inhibition of 47% of control. Postmortem tissue levels of DA, 5-hydroxytryptamine, norepinephrine and their major metabolites were determined after microinjections of GBR-12909. Tissue levels of these compounds were not significantly affected by GBR-12909. However, the ratios of homovanilic acid/DA and homovanilic acid + 3,4-dihyroxyphenylacetic acid/DA were significantly decreased, whereas the 5-hydroxyindoleacetic acid/5-hydroxytryptamine ratio was not affected by GBR-12909, suggesting a selective effect on DAergic processes. By itself, R-(+)-SCH-23390 had no effect on locomotor activity except at a very high dose which caused locomotor inhibition (49% of control). Epidepride caused a dose-dependent inhibition of locomotor activity with a maximum inhibition of 49% of control. When coinjected with an inhibitory dose of GBR-12909, both epidepride and R-(+)-SCH-23390 attenuated the GBR-12909 effect in a dose-dependent manner. A broad range of doses of NT was found to have no consistent effect on locomotor activity. However, when coinjected with an inhibitory dose of GBR-12909, NT attenuated the GBR-12909-induced inhibition in a dose-dependent manner. The results suggest that stimulation of DA receptors in the mPFC, both DA D1 and DA D2 receptors mediates locomotor inhibition. Furthermore, stimulation of NT receptors appears to

  4. Effects of serotonergic medications on locomotor performance in humans with incomplete spinal cord injury.

    PubMed

    Leech, Kristan A; Kinnaird, Catherine R; Hornby, T George

    2014-08-01

    Incomplete spinal cord injury (iSCI) often results in significant motor impairments that lead to decreased functional mobility. Loss of descending serotonergic (5HT) input to spinal circuits is thought to contribute to motor impairments, with enhanced motor function demonstrated through augmentation of 5HT signaling. However, the presence of spastic motor behaviors in SCI is attributed, in part, to changes in spinal 5HT receptors that augment their activity in the absence of 5HT, although data demonstrating motor effects of 5HT agents that deactivate these receptors are conflicting. The effects of enhancement or depression of 5HT signaling on locomotor function have not been thoroughly evaluated in human iSCI. Therefore, the aim of the current study was to investigate acute effects of 5HT medications on locomotion in 10 subjects with chronic (>1 year) iSCI. Peak overground and treadmill locomotor performance, including measures of gait kinematics, electromyographic (EMG) activity, and oxygen consumption, were assessed before and after single-dose administration of either a selective serotonin reuptake inhibitor (SSRI) or a 5HT antagonist using a double-blinded, randomized, cross-over design. Results indicate that neither medication led to improvements in locomotion, with a significant decrease in peak overground gait speed observed after 5HT antagonists (from 0.8±0.1 to 0.7±0.1 m/s; p=0.01). Additionally, 5-HT medications had differential effects on EMG activity, with 5HT antagonists decreasing extensor activity and SSRIs increasing flexor activity. Our data therefore suggest that acute manipulation of 5HT signaling, despite changes in muscle activity, does not improve locomotor performance after iSCI. PMID:24742292

  5. Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

    PubMed

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

    2015-01-01

    Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions. PMID:25859655

  6. Human spinal locomotor control is based on flexibly organized burst generators.

    PubMed

    Danner, Simon M; Hofstoetter, Ursula S; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

    2015-03-01

    Constant drive provided to the human lumbar spinal cord by epidural electrical stimulation can cause local neural circuits to generate rhythmic motor outputs to lower limb muscles in people paralysed by spinal cord injury. Epidural spinal cord stimulation thus allows the study of spinal rhythm and pattern generating circuits without their configuration by volitional motor tasks or task-specific peripheral feedback. To reveal spinal locomotor control principles, we studied the repertoire of rhythmic patterns that can be generated by the functionally isolated human lumbar spinal cord, detected as electromyographic activity from the legs, and investigated basic temporal components shared across these patterns. Ten subjects with chronic, motor-complete spinal cord injury were studied. Surface electromyographic responses to lumbar spinal cord stimulation were collected from quadriceps, hamstrings, tibialis anterior, and triceps surae in the supine position. From these data, 10-s segments of rhythmic activity present in the four muscle groups of one limb were extracted. Such samples were found in seven subjects. Physiologically adequate cycle durations and relative extension- and flexion-phase durations similar to those needed for locomotion were generated. The multi-muscle activation patterns exhibited a variety of coactivation, mixed-synergy and locomotor-like configurations. Statistical decomposition of the electromyographic data across subjects, muscles and samples of rhythmic patterns identified three common temporal components, i.e. basic or shared activation patterns. Two of these basic patterns controlled muscles to contract either synchronously or alternatingly during extension- and flexion-like phases. The third basic pattern contributed to the observed muscle activities independently from these extensor- and flexor-related basic patterns. Each bifunctional muscle group was able to express both extensor- and flexor-patterns, with variable ratios across the

  7. Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents.

    PubMed

    Gatch, Michael B; Dolan, Sean B; Forster, Michael J

    2016-09-01

    5,6-Methylenedioxy-2-aminoindane (MDAI) has become a common substitute for (±)-3,4-methylenedioxymethamphetamine (MDMA) in Ecstasy. MDAI is known to produce MDMA-like discriminative stimulus effects, but it is not known whether MDAI has psychostimulant or hallucinogen-like effects. MDAI was tested for locomotor stimulant effects in mice and subsequently for discriminative stimulus effects in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally), methamphetamine (1 mg/kg, intraperitoneally), ±MDMA (1.5 mg/kg, intraperitoneally), or (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (0.5 mg/kg, intraperitoneally) from saline. The ability of MDAI to produce conditioned place preference was also tested in mice. MDAI (3 to 30 mg/kg) depressed locomotor activity from 10 to 60 min. A rebound stimulant effect was observed at 1 to 3.5 h following 30 mg/kg. Lethality occurred in 8/8 mice following 100 mg/kg MDAI. Similarly, MDMA depressed locomotor activity immediately following the administration of 0.25 mg/kg and stimulant effects were observed 50-70 min following the administration of 0.5 and 1 mg/kg. MDAI fully substituted for the discriminative stimulus effects of MDMA (2.5 mg/kg), (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (5 mg/kg), and cocaine (7.5 mg/kg), but produced only 73% methamphetamine-appropriate responding at a dose that suppressed responding (7.5 mg/kg). MDAI produced tremors at 10 mg/kg in one methamphetamine-trained rat. MDAI produced conditioned place preference from 0.3 to 10 mg/kg. The effects of MDAI on locomotor activity and drug discrimination were similar to those produced by MDMA, having both psychostimulant-like and hallucinogen-like effects; thus, MDAI may have similar abuse potential as MDMA. PMID:27028902

  8. The role of the serotonergic system in locomotor recovery after spinal cord injury

    PubMed Central

    Ghosh, Mousumi; Pearse, Damien D.

    2015-01-01

    Serotonin (5-HT), a monoamine neurotransmitter synthesized in various populations of brainstem neurons, plays an important role in modulating the activity of spinal networks involved in vertebrate locomotion. Following spinal cord injury (SCI) there is a disruption of descending serotonergic projections to spinal motor areas, which results in a subsequent depletion in 5-HT, the dysregulation of 5-HT transporters as well as the elevated expression, super-sensitivity and/or constitutive auto-activation of specific 5-HT receptors. These changes in the serotonergic system can produce varying degrees of locomotor dysfunction through to paralysis. To date, various approaches targeting the different components of the serotonergic system have been employed to restore limb coordination and improve locomotor function in experimental models of SCI. These strategies have included pharmacological modulation of serotonergic receptors, through the administration of specific 5-HT receptor agonists, or by elevating the 5-HT precursor 5-hydroxytryptophan, which produces a global activation of all classes of 5-HT receptors. Stimulation of these receptors leads to the activation of the locomotor central pattern generator (CPG) below the site of injury to facilitate or improve the quality and frequency of movements, particularly when used in concert with the activation of other monoaminergic systems or coupled with electrical stimulation. Another approach has been to employ cell therapeutics to replace the loss of descending serotonergic input to the CPG, either through transplanted fetal brainstem 5-HT neurons at the site of injury that can supply 5-HT to below the level of the lesion or by other cell types to provide a substrate at the injury site for encouraging serotonergic axon regrowth across the lesion to the caudal spinal cord for restoring locomotion. PMID:25709569

  9. Enhanced locomotor adaptation aftereffect in the “broken escalator” phenomenon using anodal tDCS

    PubMed Central

    Kaski, D.; Quadir, S.; Patel, M.; Yousif, N.

    2012-01-01

    The everyday experience of stepping onto a stationary escalator causes a stumble, despite our full awareness that the escalator is broken. In the laboratory, this “broken escalator” phenomenon is reproduced when subjects step onto an obviously stationary platform (AFTER trials) that was previously experienced as moving (MOVING trials) and attests to a process of motor adaptation. Given the critical role of M1 in upper limb motor adaptation and the potential for transcranial direct current stimulation (tDCS) to increase cortical excitability, we hypothesized that anodal tDCS over leg M1 and premotor cortices would increase the size and duration of the locomotor aftereffect. Thirty healthy volunteers received either sham or real tDCS (anodal bihemispheric tDCS; 2 mA for 15 min at rest) to induce excitatory effects over the primary motor and premotor cortex before walking onto the moving platform. The real tDCS group, compared with sham, displayed larger trunk sway and increased gait velocity in the first AFTER trial and a persistence of the trunk sway aftereffect into the second AFTER trial. We also used transcranial magnetic stimulation to probe changes in cortical leg excitability using different electrode montages and eyeblink conditioning, before and after tDCS, as well as simulating the current flow of tDCS on the human brain using a computational model of these different tDCS montages. Our data show that anodal tDCS induces excitability changes in lower limb motor cortex with resultant enhancement of locomotor adaptation aftereffects. These findings might encourage the use of tDCS over leg motor and premotor regions to improve locomotor control in patients with neurological gait disorders. PMID:22323638

  10. Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise.

    PubMed

    Cartee, Gregory D

    2015-12-15

    Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24-48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

  11. Reliability review of the remote tool delivery system locomotor

    SciTech Connect

    Chesser, J.B.

    1999-04-01

    The locomotor being built by RedZone Robotics is designed to serve as a remote tool delivery (RID) system for waste retrieval, tank cleaning, viewing, and inspection inside the high-level waste tanks 8D-1 and 8D-2 at West Valley Nuclear Services (WVNS). The RTD systm is to be deployed through a tank riser. The locomotor portion of the RTD system is designed to be inserted into the tank and is to be capable of moving around the tank by supporting itself and moving on the tank internal structural columns. The locomotor will serve as a mounting platform for a dexterous manipulator arm. The complete RTD system consists of the locomotor, dexterous manipulator arm, cameras, lights, cables, hoses, cable/hose management system, power supply, and operator control station.

  12. Locomotor stereotypy produced by dexbenzetimide and scopolamine is reduced by SKF 83566, not sulpiride.

    PubMed

    Fritts, M E; Mueller, K; Morris, L

    1998-07-01

    Like amphetamine, scopolamine produces locomotor stereotypy (repetitive routes of locomotion) in an open field. To determine whether locomotor stereotypy is a common behavioral effect of anticholingeric agents, several doses of the anticholinergic dexbenzetimide were tested for the ability to produce locomotor stereotypy; like scopolamine, dexbenzetimide produced locomotor stereotypy. To investigate a possible role of dopamine in anticholinergic-induced locomotor stereotypy, we tested the ability of the dopamine D1 antagonist SKF 83566 and the D2 antagonist sulpiride to block the locomotor stereotypy induced by scopolamine as well as dexbenzetimide. SKF 83566 blocked scopolamine- and dexbenzetimide-induced locomotor stereotypy; sulpiride did not reduce dexbenzetimide-induced locomotor stereotypy, but enhanced scopolamine-induced locomotor stereotypy. Hyperlocomotion was reduced by both dopamine antagonists. Results are interpreted in support of the notion that dopamine is the likely candidate mediating locomotor stereotypy. PMID:9678647

  13. Dose-dependent changes in the locomotor responses to methamphetamine in BALB/c mice: Low doses induce hypolocomotion

    PubMed Central

    Singh, Rana A. K.; Kosten, Therese A.; Kinsey, Berma M.; Shen, Xiaoyun; Lopez, Angel Y.; Kosten, Thomas R.; Orson, Frank M.

    2012-01-01

    The overall goal of the present study was to determine the effects of different doses of (+)-methamphetamine (meth) on locomotor activity of Balb/C mice. Four experiments were designed to test a wide range of meth doses in BALB/c female mice. In Experiment 1, we examined locomotor activity induced by an acute administration of low doses of meth (0.01 and 0.03 mg/kg) in a 90-min session. Experiment 2 was conducted to test higher meth doses (0.3 – 10 mg/kg). In Experiment 3, separate sets of mice were pre-treated with various meth doses once or twice (one injection/week) prior to a locomotor challenge with a low meth dose. Finally, in Experiment 4, we tested whether locomotor activation would be affected by pretreatment with a low or moderate dose of meth one month prior to the low meth dose challenge. Results show that low doses of meth induce hypolocomotion whereas moderate to high doses induce hyperlocomotion. Prior exposure to either one moderate or high dose of meth or to two, low doses of meth attenuated the hypolocomotor effect of a low meth dose one week later. This effect was also attenuated in mice tested one month after administration of a moderate meth dose. These results show that low and high doses of meth can have opposing effects on locomotor activity. Further, prior exposure to the drug leads to tolerance, rather than sensitization, of the hypolocomotor response to low meth doses. PMID:23010423

  14. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure

    PubMed Central

    Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K.; Bechmann, Lars P.; Gerken, Guido; Moeller, Lars C.; Canbay, Ali

    2015-01-01

    Introduction Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. Methods 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. Results More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. Conclusions In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity. PMID:26147961

  15. Acute stimulation of mesenchymal stem cells with cigarette smoke extract affects their migration, differentiation, and paracrine potential

    PubMed Central

    Wahl, Elizabeth A.; Schenck, Thilo L.; Machens, Hans-Günther; Egaña, J. Tomás

    2016-01-01

    Mesenchymal stem cells (MSCs) are known to play a key role in tissue regeneration, while smoking cigarettes is described to impair it. This work focuses on the effect cigarette smoke extract (CSE) has on the migration, differentiation, and paracrine potential of human adipose derived MSCs (AdMSCs). To mimic native conditions in vitro, AdMSCs were cultured in either monolayer or three-dimensional pellet cultures. While constant exposure to high concentrations of CSE had lethal effects on AdMSCs, lower concentrations of CSE impaired cell migration when compared to control conditions. The secretion of key interleukins was downregulated when CSE was exposed to the cells at low concentrations. Moreover, in this work AdMSCs were exposed to CSE while simultaneously being induced to differentiate into adipocytes, osteoblasts, and chondrocytes to determine the effect of CSE on the cells potential to differentiate. While adipogenic differentiation showed no significant variation, AdMSCs exposed to osteogenic and chondrogenic supplements showed both early and late genetic level variation when acutely exposed to low concentrations of CSE. Our results indicate that even a small amount of cigarette smoke can have detrimental effects on the regenerative potential of MSCs. PMID:26976359

  16. Na,K-ATPase α2 activity in mammalian skeletal muscle T-tubules is acutely stimulated by extracellular K+

    PubMed Central

    Hakimjavadi, Hesamedin; Lingrel, Jerry B.

    2015-01-01

    The Na,K-ATPase α2 isoform is the predominant Na,K-ATPase in adult skeletal muscle and the sole Na,K-ATPase in the transverse tubules (T-tubules). In quiescent muscles, the α2 isozyme operates substantially below its maximal transport capacity. Unlike the α1 isoform, the α2 isoform is not required for maintaining resting ion gradients or the resting membrane potential, canonical roles of the Na,K-ATPase in most other cells. However, α2 activity is stimulated immediately upon the start of contraction and, in working muscles, its contribution is crucial to maintaining excitation and resisting fatigue. Here, we show that α2 activity is determined in part by the K+ concentration in the T-tubules, through its K+ substrate affinity. Apparent K+ affinity was determined from measurements of the K1/2 for K+ activation of pump current in intact, voltage-clamped mouse flexor digitorum brevis muscle fibers. Pump current generated by the α2 Na,K-ATPase, Ip, was identified as the outward current activated by K+ and inhibited by micromolar ouabain. Ip was outward at all potentials studied (−90 to −30 mV) and increased with depolarization in the subthreshold range, −90 to −50 mV. The Q10 was 2.1 over the range of 22–37°C. The K1/2,K of Ip was 4.3 ± 0.3 mM at −90 mV and was relatively voltage independent. This K+ affinity is lower than that reported for other cell types but closely matches the dynamic range of extracellular K+ concentrations in the T-tubules. During muscle contraction, T-tubule luminal K+ increases in proportion to the frequency and duration of action potential firing. This K1/2,K predicts a low fractional occupancy of K+ substrate sites at the resting extracellular K+ concentration, with occupancy increasing in proportion to the frequency of membrane excitation. The stimulation of preexisting pumps by greater K+ site occupancy thus provides a rapid mechanism for increasing α2 activity in working muscles. PMID:26371210

  17. Salicylate acutely stimulates 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscles.

    PubMed

    Serizawa, Yasuhiro; Oshima, Rieko; Yoshida, Mitsuki; Sakon, Ichika; Kitani, Kazuto; Goto, Ayumi; Tsuda, Satoshi; Hayashi, Tatsuya

    2014-10-10

    Salicylate (SAL) has been recently implicated in the antidiabetic effect in humans. We assessed whether 5'-AMP-activated protein kinase (AMPK) in skeletal muscle is involved in the effect of SAL on glucose homeostasis. Rat fast-twitch epitrochlearis and slow-twitch soleus muscles were incubated in buffer containing SAL. Intracellular concentrations of SAL increased rapidly (<5 min) in both skeletal muscles, and the Thr(172) phosphorylation of the α subunit of AMPK increased in a dose- and time-dependent manner. SAL increased both AMPKα1 and AMPKα2 activities. These increases in enzyme activity were accompanied by an increase in the activity of 3-O-methyl-D-glucose transport, and decreases in ATP, phosphocreatine, and glycogen contents. SAL did not change the phosphorylation of insulin receptor signaling including insulin receptor substrate 1, Akt, and p70 ribosomal protein S6 kinase. These results suggest that SAL may be transported into skeletal muscle and may stimulate AMPK and glucose transport via energy deprivation in multiple muscle types. Skeletal muscle AMPK might be part of the mechanism responsible for the metabolic improvement induced by SAL. PMID:25256746

  18. Astrocytes Are Primed by Chronic Neurodegeneration to Produce Exaggerated Chemokine and Cell Infiltration Responses to Acute Stimulation with the Cytokines IL-1β and TNF-α

    PubMed Central

    Hennessy, Edel; Griffin, Éadaoin W.

    2015-01-01

    Microgliosis and astrogliosis are standard pathological features of neurodegenerative disease. Microglia are primed by chronic neurodegeneration such that toll-like receptor agonists, such as LPS, drive exaggerated cytokine responses on this background. However, sterile inflammatory insults are more common than direct CNS infection in the degenerating brain and these insults drive robust IL-1β and TNF-α responses. It is unclear whether these pro-inflammatory cytokines can directly induce exaggerated responses in the degenerating brain. We hypothesized that glial cells in the hippocampus of animals with chronic neurodegenerative disease (ME7 prion disease) would display exaggerated responses to central cytokine challenges. TNF-α or IL-1β were administered intrahippocampally to ME7-inoculated mice and normal brain homogenate-injected (NBH) controls. Both IL-1β and TNF-α produced much more robust IL-1β synthesis in ME7 than in NBH animals and this occurred exclusively in microglia. However, there was strong nuclear localization of the NFκB subunit p65 in the astrocyte population, associated with marked astrocytic synthesis of the chemokines CXCL1 and CCL2 in response to both cytokine challenges in ME7 animals. Conversely, very limited expression of these chemokines was apparent in NBH animals similarly challenged. Thus, astrocytes are primed in the degenerating brain to produce exaggerated chemokine responses to acute stimulation with pro-inflammatory cytokines. Furthermore, this results in markedly increased neutrophil, T-cell, and monocyte infiltration in the diseased brain. These data have significant implications for acute sterile inflammatory insults such as stroke and traumatic brain injury occurring on a background of aging or neurodegeneration. PMID:26041910

  19. Vagal nerve stimulation blocks interleukin 6-dependent synaptic hyperexcitability induced by lipopolysaccharide-induced acute stress in the rodent prefrontal cortex.

    PubMed

    Garcia-Oscos, Francisco; Peña, David; Housini, Mohammad; Cheng, Derek; Lopez, Diego; Borland, Michael S; Salgado-Delgado, Roberto; Salgado, Humberto; D'Mello, Santosh; Kilgard, Michael P; Rose-John, Stefan; Atzori, Marco

    2015-01-01

    The ratio between synaptic inhibition and excitation (sI/E) is a critical factor in the pathophysiology of neuropsychiatric disease. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in sI/E in the rodent temporal cortex. The aim of the present study was to determine whether a similar mechanism takes place in the prefrontal cortex, and to elaborate strategies to prevent or attenuate it. We used aseptic inflammation (single acute injections of lipopolysaccharide, LPS, 10mg/kg) as stress model, and patch-clamp recording on a prefrontal cortical slice preparation from wild-type rat and mice, as well as from transgenic mice in which the inhibitor of IL-6 trans-signaling sgp130Fc was produced in a brain-specific fashion (sgp130Fc mice). The anti-inflammatory reflex was activated either by vagal nerve stimulation or peripheral administration of the nicotinic α7 receptor agonist PHA543613. We found that the IL-6-dependent reduction in prefrontal cortex synaptic inhibition was blocked in sgp130Fc mice, or - in wild-type animals - upon application sgp130Fc. Similar results were obtained by activating the "anti-inflammatory reflex" - a neural circuit regulating peripheral immune response - by stimulation of the vagal nerve or through peripheral administration of the α7 nicotinic receptor agonist PHA543613. Our results indicate that the prefrontal cortex is an important potential target of IL-6 mediated trans-signaling, and suggest a potential new avenue in the treatment of a large class of hyperexcitable neuropsychiatric conditions, including epilepsy, schizophrenic psychoses, anxiety disorders, autism spectrum disorders, and depression. PMID:25128387

  20. Electroacupuncture Ameliorates Acute Renal Injury in Lipopolysaccharide-Stimulated Rabbits via Induction of HO-1 through the PI3K/Akt/Nrf2 Pathways

    PubMed Central

    Gong, Li-rong; Dong, Shu-an; Cao, Xin-shun; Wu, Li-li; Wu, Li-na

    2015-01-01

    Electroacupuncture at select acupoints have been verified to protect against organ dysfunctions during endotoxic shock. And, heme oxygenase (HO)-1 as a phase II enzyme and antioxidant contributed to the protection of kidney in septic shock rats. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway mediated the activation of NF-E2 related factor-2 (Nrf2), which was involved in HO-1 induction. To understand the efficacy of electroacupuncture stimulation in ameliorating acute kidney injury (AKI) through the PI3K/Akt/Nrf2 pathway and subsequent HO-1 upregulation, a dose of LPS 5mg/kg was administered intravenously to replicate the rabbit model of AKI induced by endotoxic shock. Electroacupuncture pretreatment was handled bilaterally at Zusanli and Neiguan acupoints for five consecutive days while sham electroacupuncture at non-acupoints as control. Results displayed that electroacupuncture stimulation significantly alleviated the morphologic renal damage, attenuated renal tubular apoptosis, suppressed the elevated biochemical indicators of AKI caused by LPS, enhanced the expressions of phospho-Akt, HO-1protein, Nrf2 total and nucleoprotein, and highlighted the proportions of Nrf2 nucleoprotein as a parallel. Furthermore, partial protective effects of elecroacupuncture were counteracted by preconditioning with wortmannin (the selective PI3K inhibitor), indicating a direct involvement of PI3K/Akt pathway. Inconsistently, wortmannin pretreatment made little difference to the expressions of HO-1, Nrf2 nucleoprotein and total protein, which indicated that PI3K/Akt may be not the only pathway responsible for electroacupuncture-afforded protection against LPS-induced AKI. These findings provide new insights into the potential future clinical applications of electroacupuncture for AKI induced by endotoxic shock instead of traditional remedies. PMID:26524181

  1. Colony-stimulating factors for the treatment of the hematopoietic component of the acute radiation syndrome (H-ARS): a review.

    PubMed

    Singh, Vijay K; Newman, Victoria L; Seed, Thomas M

    2015-01-01

    One of the greatest national security threats to the United States is the detonation of an improvised nuclear device or a radiological dispersal device in a heavily populated area. As such, this type of security threat is considered to be of relatively low risk, but one that would have an extraordinary high impact on health and well-being of the US citizenry. Psychological counseling and medical assessments would be necessary for all those significantly impacted by the nuclear/radiological event. Direct medical interventions would be necessary for all those individuals who had received substantial radiation exposures (e.g., >1 Gy). Although no drugs or products have yet been specifically approved by the United States Food and Drug Administration (US FDA) to treat the effects of acute radiation syndrome (ARS), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and pegylated G-CSF have been used off label for treating radiation accident victims. Recent threats of terrorist attacks using nuclear or radiologic devices makes it imperative that the medical community have up-to-date information and a clear understanding of treatment protocols using therapeutically effective recombinant growth factors and cytokines such as G-CSF and GM-CSF for patients exposed to injurious doses of ionizing radiation. Based on limited human studies with underlying biology, we see that the recombinants, G-CSF and GM-CSF appear to have modest, but significant medicinal value in treating radiation accident victims. In the near future, the US FDA may approve G-CSF and GM-CSF as ‘Emergency Use Authorization’ (EUA) for managing radiation-induced aplasia, an ARS-related pathology. In this article, we review the status of growth factors for the treatment of radiological/nuclear accident victims. PMID:25215458

  2. Acute effects of transcutaneous electrical diaphragmatic stimulation on respiratory pattern in COPD patients: cross-sectional and comparative clinical trial

    PubMed Central

    Cancelliero-Gaiad, Karina M.; Ike, Daniela; Pantoni, Camila B. F.; Mendes, Renata G.; Borghi-Silva, Audrey; Costa, Dirceu

    2013-01-01

    Background Transcutaneous electrical diaphragmatic stimulation (TEDS) has been used to improve respiratory muscle strength in patients with respiratory muscle weakness. However, this physical therapy resource has not been studied in chronic obstructive pulmonary disease (COPD). Objective To evaluate the respiratory pattern during one session of TEDS in COPD patients. Method Fifteen COPD patients participated in one TEDS session for plethysmographic analysis and assessment of peripheral oxygen saturation (SpO2) and heart rate (HR). After the session, patients were divided into two groups: Responder (R; n=9) and Non-Responder (NR; n=6) to TEDS. Statistic analysis was performed using the Shapiro-Wilk normality test and two-way ANOVA. For the parameters that showed interaction, the Student t test was used (P<0.05). Results R group consisted mainly of men, with lower SpO2 and higher HR than NR group. When time (before and during) and groups (R and NR) were compared (interaction), there were differences in the parameters minute ventilation (Vent), inspiratory tidal volume (ViVol), expiratory tidal volume (VeVol), and respiratory rate (Br/M). In the intergroup comparison, differences were observed in the parameters Vent, ViVol, and VeVol. A significant effect was also observed for time in change in end-expiratory lung volume level (qDEEL), phase relation during inspiration (PhRIB); phase relation during expiration (PhREB); phase relation of entire breath (PhRTB), and phase angle (PhAng). During TEDS, there was an increase in SpO2 and a reduction in HR in both groups. Conclusions The most hypoxemic group with greater HR responded to TEDS and there was interaction between group and time of analysis for the pulmonary volumes. The time factor had an influence on the two groups with an increase in thoracoabdominal asynchrony. PMID:24271095

  3. Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study

    PubMed Central

    Diener, Hans-Christoph; Silver, Nicholas; Magis, Delphine; Reuter, Uwe; Andersson, Annelie; Liebler, Eric J; Straube, Andreas

    2015-01-01

    Background Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH. Methods PREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS (n = 48) with standard of care (SoC) alone (control (n = 49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety/tolerability were also assessed. Results During the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS (n = 45) had a significantly greater reduction in the number of attacks per week vs controls (n = 48) (−5.9 vs −2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p = 0.02). Higher ≥50% response rates were also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p < 0.001). No serious treatment-related adverse events occurred. Conclusion Adjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC. PMID:26391457

  4. Does acute, intense stimulation of oxytocin neurones in the supraoptic nucleus increase their content of oxytocin mRNA?

    PubMed

    Sumner, B E; Kawata, M; Russell, J A

    1989-06-12

    We investigated whether a sustained increase in oxytocin secretion, with or without enhanced electrical activity of the cell-bodies of oxytocin neurones, leads to a rapid increase in oxytocin mRNA content in these neurones. To stimulate oxytocin release, naloxone (2.5 mg/kg i.v. twice, 30 min apart) was given to urethane-anaesthetized female rats after intracerebroventricular (i.c.v.) morphine or vehicle infusion for 5 days; in the latter, naloxone acts on the neurohypophysis to increase oxytocin release without affecting the electrical activity of oxytocin neurone cell-bodies, but in the former, naloxone acts both on the neucohypophysis and on the cell-bodies to excite them electrically. Oxytocin content in peripheral plasma was measured intermittently by radioimmunoassay for 4 h after i.v. naloxone or vehicle, then the brain was removed and cryostat sections were cut through the supraoptic nucleus (SON). Oxytocin mRNA content in individual neurones (25-50 per rat) was measured semiquantitatively by in situ hybridisation histochemistry, using a tritiated synthetic cDNA 25-mer oligonucleotide probe, autoradiographical visualisation, and computer-assisted image-analysis to measure silver grain density. Nalaxone increased oxytocin content in plasma 7-fold for at least 40 min in i.c.v. vehicle-infused rats, and 40-fold for at least 40 min in i.c.v. morphine-infused rats. Naloxone had no significant effect on the oxytocin mRNA content in labelled cells in the SON, and no effect on the proportion of labelled cells, in either the i.c.v. morphine- or i.c.v. vehicle-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2743158

  5. The Effects of 4-Methylethcathinone on Conditioned Place Preference, Locomotor Sensitization, and Anxiety-Like Behavior: A Comparison with Methamphetamine

    PubMed Central

    Xu, Peng; Qiu, Yi; Zhang, Yizhi; Βai, Yanping; Xu, Pengfei; Liu, Yuan; Kim, Jee Hyun

    2016-01-01

    Background: 4-Methylethcathinone is a drug that belongs to the second generation of synthetic cathinones, and recently it has been ranked among the most popular “legal highs”. Although it has similar in vitro neurochemical actions to other drugs such as cocaine, the behavioral effects of 4-methylethcathinone remain to be determined. Methods: The addictive potential and locomotor potentiation by 4-methylethcathinone were investigated in rats using the conditioned place preference and sensitization paradigm. Methamphetamine was used as a positive control. Because synthetic cathinones can have psychological effects, we also examined anxiety-like behavior using the elevated plus maze. Results: A conditioning dose of 10mg/kg 4-methylethcathinone was able to induce conditioned place preference and reinstatement (following 2 weeks of withdrawal). Acute or repeated injections of 4-methylethcathinone at 3 or 10mg/kg failed to alter locomotor activity. At 30mg/kg, however, acute 4-methylethcathinone increased locomotor activity compared with saline, while chronic 4-methylethcathinone induced a delayed and attenuated sensitization compared with methamphetamine. Additionally, repeated daily injections of 4-methylethcathinone (30mg/kg) reduced, whereas methamphetamine increased time spent by rats in the open arm of an elevated plus maze compared with saline injections. Interestingly, a 2-week withdrawal period following chronic injections of 4-methylethcathinone or methamphetamine increased time spent in the open arm in all rats. Conclusions: The rewarding properties of 4-methylethcathinone were found to be dissociated from its effects on locomotor activity. Additionally, chronic 4-methylethcathinone use may trigger abnormal anxious behaviors. These behavioral effects caused by 4-methylethcathinone appear to last even after a withdrawal period. PMID:26612552

  6. Optogenetic Activation of the Excitatory Neurons Expressing CaMKIIα in the Ventral Tegmental Area Upregulates the Locomotor Activity of Free Behaving Rats

    PubMed Central

    Guo, Songchao; Chen, Sicong; Zhang, Qiaosheng; Wang, Yueming; Xu, Kedi; Zheng, Xiaoxiang

    2014-01-01

    The ventral tegmental area (VTA) plays an important role in motivation and motor activity of mammals. Previous studies have reported that electrical stimulations of the VTA's neuronal projections were able to upregulate the locomotor activity of behaving rats. However, which types of neurons in the VTA that take part in the activation remain elusive. In this paper we employed optogenetic technique to selectively activate the excitatory neurons expressing CaMKIIα in the VTA region and induced a higher locomotor activity for free behaving rats. Further behavioral studies indicated that reward learning mediated in the enhancement of the rat locomotor activity. Finally the immunohistochemistry studies explored that the excitatory neurons under the optogenetic activation in VTA were partly dopaminergic that may participate as a vital role in the optogenetic activation of the locomotor activity. In total, our study provided an optogenetic approach to selectively upregulate the locomotor activity of free behaving rats, thus facilitating both neuroscience researches and neural engineering such as animal robotics in the future. PMID:24711999

  7. Quantitative changes in Galphaolf protein levels, but not D1 receptor, alter specifically acute responses to psychostimulants.

    PubMed

    Corvol, Jean-Christophe; Valjent, Emmanuel; Pascoli, Vincent; Robin, Aurélie; Stipanovich, Alexandre; Luedtke, Robert R; Belluscio, Leonardo; Girault, Jean-Antoine; Hervé, Denis

    2007-05-01

    Striatal dopamine D1 receptors (D1R) are coupled to adenylyl cyclase through Galphaolf. Although this pathway is involved in important brain functions, the consequences of quantitative alterations of its components are not known. We explored the biochemical and behavioral responses to cocaine and D-amphetamine (D-amph) in mice with heterozygous mutations of genes encoding D1R and Galphaolf (Drd1a+/- and Gnal+/-), which express decreased levels of the corresponding proteins in the striatum. Dopamine-stimulated cAMP production in vitro and phosphorylation of AMPA receptor GluR1 subunit in response to D-amph in vivo were decreased in Gnal+/-, but not Drd1a+/- mice. Acute locomotor responses to D1 agonist SKF81259, D-amph and cocaine were altered in Gnal+/- mice, and not in Drd1a+/- mice. This haploinsufficiency showed that Galphaolf but not D1R protein levels are limiting for D1R-mediated biochemical and behavioral responses. Gnal+/- mice developed pronounced locomotor sensitization and conditioned locomotor responses after repeated injections of D-amph (2 mg/kg) or cocaine (20 mg/kg). They also developed normal D-amph-conditioned place preference. The D1R/cAMP pathway remained blunted in repeatedly treated Gnal+/- mice. In contrast, D-amph-induced ERK activation was normal in the striatum of these mice, possibly accounting for the normal development of long-lasting behavioral responses to psychostimulants. Our results clearly dissociate biochemical mechanisms involved in acute and delayed behavioral effects of psychostimulants. They identify striatal levels of Galphaolf as a key factor for acute responses to psychostimulants and suggest that quantitative alterations of its expression may alter specific responses to drugs of abuse, or possibly other behavioral responses linked to dopamine function. PMID:17063155

  8. Granulocyte colony-stimulating factor does not enhance recruitment of bone marrow-derived cells in rats with acute myocardial infarction.

    PubMed

    Sato, Daisuke; Otani, Hajime; Fujita, Masanori; Shimazu, Takayuki; Yoshioka, Kei; Enoki, Chiharu; Minato, Naoki; Iwasaka, Toshiji

    2012-09-01

    Despite the potential benefit of granulocyte colony-stimulating factor (G-CSF) therapy in patients with acute myocardial infarction (MI), the efficacy of G-CSF in regenerating the heart after MI remains controversial. The authors hypothesize that the limited efficacy of G-CSF is related to its inhibitory effect on recruitment of bone marrow-derived cells (BMCs) to the infarcted tissue. MI was induced in rats with intrabone marrow-bone marrow transplantation from syngenic rats expressing green fluorescence protein to track BMCs. G-CSF was administered for five days after the onset of MI. G-CSF increased the number of CD45(+) cells in the peripheral circulation but did not increase their recruitment to the heart. G-CSF had no effect on myocardial stromal-derived factor-1 alpha and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in mononuclear cells in the peripheral blood and CXCR4(+) cells in the heart. G-CSF had no effect on angiogenesis, myocardial fibrosis or left ventricular function four weeks after MI. These results suggest that G-CSF mobilizes BMCs to the peripheral circulation but does not increase recruitment to the infarcted myocardium despite preservation of the stromal-derived factor-1 alpha/CXCR4 axis. PMID:23620693

  9. Bile acids acutely stimulate insulin secretion of mouse β-cells via farnesoid X receptor activation and K(ATP) channel inhibition.

    PubMed

    Düfer, Martina; Hörth, Katrin; Wagner, Rebecca; Schittenhelm, Björn; Prowald, Susanne; Wagner, Thomas F J; Oberwinkler, Johannes; Lukowski, Robert; Gonzalez, Frank J; Krippeit-Drews, Peter; Drews, Gisela

    2012-06-01

    Type 2 diabetes mellitus is associated with alterations in bile acid (BA) signaling. The aim of our study was to test whether pancreatic β-cells contribute to BA-dependent regulation of glucose homeostasis. Experiments were performed with islets from wild-type, farnesoid X receptor (FXR) knockout (KO), and β-cell ATP-dependent K(+) (K(ATP)) channel gene SUR1 (ABCC8) KO mice, respectively. Sodium taurochenodeoxycholate (TCDC) increased glucose-induced insulin secretion. This effect was mimicked by the FXR agonist GW4064 and suppressed by the FXR antagonist guggulsterone. TCDC and GW4064 stimulated the electrical activity of β-cells and enhanced cytosolic Ca(2+) concentration ([Ca(2+)](c)). These effects were blunted by guggulsterone. Sodium ursodeoxycholate, which has a much lower affinity to FXR than TCDC, had no effect on [Ca(2+)](c) and insulin secretion. FXR activation by TCDC is suggested to inhibit K(ATP) current. The decline in K(ATP) channel activity by TCDC was only observed in β-cells with intact metabolism and was reversed by guggulsterone. TCDC did not alter insulin secretion in islets of SUR1-KO or FXR-KO mice. TCDC did not change islet cell apoptosis. This is the first study showing an acute action of BA on β-cell function. The effect is mediated by FXR by nongenomic elements, suggesting a novel link between FXR activation and K(ATP) channel inhibition. PMID:22492528

  10. Developmental Deltamethrin Exposure Causes Persistent Changes in Dopaminergic Gene Expression, Neurochemistry, and Locomotor Activity in Zebrafish

    PubMed Central

    Kung, Tiffany S.; Richardson, Jason R.; Cooper, Keith R.; White, Lori A.

    2015-01-01

    Pyrethroids are commonly used insecticides that are considered to pose little risk to human health. However, there is an increasing concern that children are more susceptible to the adverse effects of pesticides. We used the zebrafish model to test the hypothesis that developmental exposure to low doses of the pyrethroid deltamethrin results in persistent alterations in dopaminergic gene expression, neurochemistry, and locomotor activity. Zebrafish embryos were treated with deltamethrin (0.25–0.50 μg/l), at concentrations below the LOAEL, during the embryonic period [3–72 h postfertilization (hpf)], after which transferred to fresh water until the larval stage (2-weeks postfertilization). Deltamethrin exposure resulted in decreased transcript levels of the D1 dopamine (DA) receptor (drd1) and increased levels of tyrosine hydroxylase at 72 hpf. The reduction in drd1 transcripts persisted to the larval stage and was associated with decreased D2 dopamine receptor transcripts. Larval fish, exposed developmentally to deltamethrin, had increased levels of homovanillic acid, a DA metabolite. Since the DA system is involved in locomotor activity, we measured the swim activity of larval fish following a transition to darkness. Developmental exposure to deltamethrin significantly increased larval swim activity which was attenuated by concomitant knockdown of the DA transporter. Acute exposure to methylphenidate, a DA transporter inhibitor, increased swim activity in control larva, while reducing swim activity in larva developmentally exposed to deltamethrin. Developmental exposure to deltamethrin causes locomotor deficits in larval zebrafish, which is likely mediated by dopaminergic dysfunction. This highlights the need to understand the persistent effects of low-dose neurotoxicant exposure during development. PMID:25912032

  11. An innovative spinal cord injury model for the study of locomotor networks.

    PubMed

    Nistri, A

    2012-03-01

    An acute lesion to the spinal cord triggers complex mechanisms responsible for amplification of the initial damage and its chronicity. In vitro preparations of the rodent spinal cord retain the intrinsic ability to produce locomotor-like discharges from lumbar ventral roots and, thus, offer the opportunity to study the still unclear process of lesion progression in relation to cell number and topography. In addition, these models enable a detailed approach to the molecular mechanisms of damage and to pharmacological tools to counteract them. Using the rat spinal cord in vitro, our laboratory has shown how to reliably produce discrete lesions by applying the glutamate agonist kainate that evokes delayed neuronal loss via a non-apoptotic cell death mechanism termed parthanatos. Parthanatos is believed to be due to mitochondrial damage and exhaustion of cell energy stores caused by hyperactivation of enzymatic systems initially set to repair DNA damage. Locomotor network activity is irreversibly destroyed by kainate in a virtually all-or-none manner, suggesting destruction of a highly-vulnerable cell population crucial for the expression of locomotion. Hypoxic challenge to the spinal cord together with toxic radicals primarily damages white matter cells with deficit (without full suppression) of locomotor network function, while neurons are less vulnerable. Pharmacological agents to inhibit different targets involved in the early pathophysiology of spinal injury provided limited success, indicating that novel approaches based on newly identified steps in the biochemical cascade leading to cell death should be investigated for their potential to improve the outcome of spinal cord injury. PMID:22407008

  12. Developmental Deltamethrin Exposure Causes Persistent Changes in Dopaminergic Gene Expression, Neurochemistry, and Locomotor Activity in Zebrafish.

    PubMed

    Kung, Tiffany S; Richardson, Jason R; Cooper, Keith R; White, Lori A

    2015-08-01

    Pyrethroids are commonly used insecticides that are considered to pose little risk to human health. However, there is an increasing concern that children are more susceptible to the adverse effects of pesticides. We used the zebrafish model to test the hypothesis that developmental exposure to low doses of the pyrethroid deltamethrin results in persistent alterations in dopaminergic gene expression, neurochemistry, and locomotor activity. Zebrafish embryos were treated with deltamethrin (0.25-0.50 μg/l), at concentrations below the LOAEL, during the embryonic period [3-72 h postfertilization (hpf)], after which transferred to fresh water until the larval stage (2-weeks postfertilization). Deltamethrin exposure resulted in decreased transcript levels of the D1 dopamine (DA) receptor (drd1) and increased levels of tyrosine hydroxylase at 72 hpf. The reduction in drd1 transcripts persisted to the larval stage and was associated with decreased D2 dopamine receptor transcripts. Larval fish, exposed developmentally to deltamethrin, had increased levels of homovanillic acid, a DA metabolite. Since the DA system is involved in locomotor activity, we measured the swim activity of larval fish following a transition to darkness. Developmental exposure to deltamethrin significantly increased larval swim activity which was attenuated by concomitant knockdown of the DA transporter. Acute exposure to methylphenidate, a DA transporter inhibitor, increased swim activity in control larva, while reducing swim activity in larva developmentally exposed to deltamethrin. Developmental exposure to deltamethrin causes locomotor deficits in larval zebrafish, which is likely mediated by dopaminergic dysfunction. This highlights the need to understand the persistent effects of low-dose neurotoxicant exposure during development. PMID:25912032

  13. Modular diversification of the locomotor system in damselfishes (Pomacentridae).

    PubMed

    Aguilar-Medrano, Rosalía; Frédérich, Bruno; Barber, Paul H

    2016-05-01

    As fish move and interact with their aquatic environment by swimming, small morphological variations of the locomotor system can have profound implications on fitness. Damselfishes (Pomacentridae) have inhabited coral reef ecosystems for more than 50 million years. As such, habitat preferences and behavior could significantly constrain the morphology and evolvability of the locomotor system. To test this hypothesis, we used phylogenetic comparative methods on morphometric, ecological and behavioral data. While body elongation represented the primary source of variation in the locomotor system of damselfishes, results also showed a diverse suite of morphological combinations between extreme morphologies. Results show clear associations between behavior, habitat preferences, and morphology, suggesting ecological constraints on shape diversification of the locomotor system. In addition, results indicate that the three modules of the locomotor system are weakly correlated, resulting in versatile and independent characters. These results suggest that Pomacentridae is shape may result from the interaction between (1) integrated parts of morphological variation that maintain overall swimming ability and (2) relatively independent parts of the morphology that facilitate adaptation and diversification. J. Morphol. 277:603-614, 2016. © 2016 Wiley Periodicals, Inc. PMID:26919129

  14. The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

    PubMed

    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. PMID:27237044

  15. Rotation, locomotor activity and individual differences in voluntary ethanol consumption.

    PubMed

    Nielsen, D M; Crosley, K J; Keller, R W; Glick, S D; Carlson, J N

    1999-03-27

    Spontaneous turning behavior and locomotor activity were evaluated for their ability to predict differences in the voluntary consumption of ethanol in male Long-Evans rats. Animals were assessed for their preferred direction of turning behavior and for high vs. low levels of spontaneous locomotor activity, as determined during nocturnal testing in a rotometer. Subsequently, preference for a 10% ethanol solution vs. water was determined in a 24-h two-bottle home-cage free-choice paradigm. Rats exhibiting a right-turning preference consumed more ethanol than rats showing a left-turning preference. While locomotor activity alone did not predict differences in drinking, turning and locomotor activity together predicted differences in ethanol consumption. Low-activity right-turning rats consumed more ethanol than all the other groups of rats. Previous studies from this laboratory have shown that individual differences in turning behavior are accompanied by different asymmetries in dopamine (DA) function in the medial prefrontal cortex (mPFC). Individual differences in locomotor activity are associated with differences in nucleus accumbens (NAS) DA function. The present data suggest that variations in mPFC DA asymmetry and NAS DA function may underlie differences in the voluntary consumption of ethanol. PMID:10095014

  16. The combined depletion of monoamines alters the effectiveness of subthalamic deep brain stimulation.

    PubMed

    Faggiani, Emilie; Delaville, Claire; Benazzouz, Abdelhamid

    2015-10-01

    Non-motor symptoms of Parkinson's disease are under-studied and therefore not well treated. Here, we investigated the role of combined depletions of dopamine, norepinephrine and/or serotonin in the manifestation of motor and non-motor deficits in the rat. Then, we studied the impact of these depletions on the efficacy of deep brain stimulation of the subthalamic nucleus (STN-DBS). We performed selective depletions of dopamine, norepinephrine and serotonin, and the behavioral effects of different combined depletions were investigated using the open field, the elevated plus maze and the forced swim test. Bilateral dopamine depletion alone induced locomotor deficits associated with anxiety and mild "depressive-like" behaviors. Although additional depletions of norepinephrine and/or serotonin did not potentiate locomotor and anxiety disorders, combined depletions of the three monoamines dramatically exacerbated "depressive-like" behavior. STN-DBS markedly reversed locomotor deficits and anxiety behavior in animals with bilateral dopamine depletion alone. However, these improvements were reduced or lost by the additional depletion of norepinephrine and/or serotonin, indicating that the depletion of these monoamines may interfere with the antiparkinsonian efficacy of STN-DBS. Furthermore, our results showed that acute STN-DBS improved "depressive-like" disorder in animals with bilateral depletion of dopamine and also in animals with combined depletions of the three monoamines, which induced severe immobility in the forced swim test. Our data highlight the key role of monoamine depletions in the pathophysiology of anxiety and depressive-like disorders and provide the first evidence of their negative consequences on the efficacy of STN-DBS upon the motor and anxiety disorders in the context of Parkinson's disease. PMID:26206409

  17. Dietary β-glucan stimulate complement and C-reactive protein acute phase responses in common carp (Cyprinus carpio) during an Aeromonas salmonicida infection.

    PubMed

    Pionnier, Nicolas; Falco, Alberto; Miest, Joanna; Frost, Patrick; Irnazarow, Ilgiz; Shrive, Annette; Hoole, Dave

    2013-03-01

    The effect of β-glucans as feed additive on the profile of C-reactive protein (CRP) and complement acute phase responses was studied in common carp Cyprinus carpio after exposition to a bacterial infection with Aeromonas salmonicida. Carp were orally administered with β-glucan (MacroGard®) for 14 days with a daily β-glucan intake of 6 mg per kg body weight. Fish were then intraperitoneally injected with either PBS or 1 × 10⁸ bacteria per fish and sampled at time 0, 6, 12, 24, 48, 72, 96 and 120 h post-injection (p.i.) for serum and head kidney, liver and mid-gut tissues. CRP levels and complement activity were determined in the serum samples whilst the gene expression profiles of CRP and complement related genes (crp1, crp2, c1r/s, bf/c2, c3 and masp2) were analysed in the tissues by quantitative PCR. Results obtained showed that oral administration of β-glucan for 14 days significantly increased serum CRP levels up to 2 fold and serum alternative complement activity (ACP) up to 35 fold. The bacterial infection on its own (i.e. not combined with a β-glucan feeding) did have significant effects on complement response whilst CRP was not detectably induced during the carp acute phase reaction. However, the combination of the infection and the β-glucan feeding did show significant effects on both CRP and complement profiles with higher serum CRP levels and serum ACP activity in the β-glucan fed fish than in the control fed fish. In addition, a distinct organ and time dependent expression profile pattern was detected for all the selected genes: a peak of gene expression first occurred in the head kidney tissue (6 h p.i. or 12 h p.i.), then an up-regulation in the liver several hours later (24 h p.i.) and finally up- or down-regulations in the mid-gut at 24 h p.i. and 72 h p.i. In conclusion, the results of this study suggest that MacroGard® stimulated CRP and complement responses to A. salmonicida infection in common carp. PMID:23291104

  18. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

  19. Developing Sensorimotor Countermeasures to Mitigate Post-Flight Locomotor Dysfunction

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Mulavara, A. P.; Cohen, H.; Miller, C. A.; Richards, J. T.; Houser, J.; McDonald, P. V.; Seidler, R. D.; Merkle, L. A.; Stelmach, G. E.

    2001-01-01

    Following spaceflight, crewmembers experience postural and locomotor instability. The magnitude and duration of post-flight sensorimotor disturbances increase with longer duration exposure to microgravity. These post-flight postural and locomotor alterations can pose a risk to crew safety and to mission objectives if nominal or emergency vehicle egress is required immediately following long-duration spaceflight. Gait instabilities could prevent or extend the time required to make an emergency egress from the Orbiter, Crew Return Vehicle or a future Martian lander leading to compromised mission objectives. We propose a countermeasure that aids in maintaining functional locomotor performance. This includes retaining the ability to perform vehicular egress and meet early mission objectives soon after landing on a planetary surface.

  20. Role of proinflammatory cytokines on lipopolysaccharide-induced phase shifts in locomotor activity circadian rhythm.

    PubMed

    Leone, M Juliana; Marpegan, Luciano; Duhart, José M; Golombek, Diego A

    2012-07-01

    We previously reported that early night peripheral bacterial lipopolysaccharide (LPS) injection produces phase delays in the circadian rhythm of locomotor activity in mice. We now assess the effects of proinflammatory cytokines on circadian physiology, including their role in LPS-induced phase shifts. First, we investigated whether differential systemic induction of classic proinflammatory cytokines could explain the time-specific behavioral effects of peripheral LPS. Induction levels for plasma interleukin (IL)-1α, IL-1β, IL-6, or tumor necrosis factor (TNF)-α did not differ between animals receiving a LPS challenge in the early day or early night. We next tested the in vivo effects of central proinflammatory cytokines on circadian physiology. We found that intracerebroventricular (i.c.v.) delivery of TNF-α or interleukin IL-1β induced phase delays on wheel-running activity rhythms. Furthermore, we analyzed if these cytokines mediate the LPS-induced phase shifts and found that i.c.v. administration of soluble TNF-α receptor (but not an IL-1β antagonistic) prior to LPS stimulation inhibited the phase delays. Our work suggests that the suprachiasmatic nucleus (SCN) responds to central proinflammatory cytokines in vivo, producing phase shifts in locomotor activity rhythms. Moreover, we show that the LPS-induced phase delays are mediated through the action of TNF-α at the central level, and that systemic induction of proinflammatory cytokines might be necessary, but not sufficient, for this behavioral outcome. PMID:22734572

  1. Association of locomotor complaints and disability in the Rotterdam study.

    PubMed Central

    Odding, E; Valkenburg, H A; Algra, D; Vandenouweland, F A; Grobbee, D E; Hofman, A

    1995-01-01

    OBJECTIVE--To determine the association between joint complaints and locomotor disability. METHODS--During a home interview survey 1901 men and 3135 women aged 55 years and over (the Rotterdam Study) were asked about joint pain and morning stiffness in the past month, and locomotor disability was assessed by six questions from the Health Assessment Questionnaire (HAQ). RESULTS--The prevalence of locomotor disability was 24.5% for men and 40.5% for women. The prevalence of joint pain in men was 0.7% for pain in the hips, knees, and feet simultaneously, 3.7% for pain at two joint sites, 16.0% for pain at one joint site, and 20.4% for pain in the hips and/or knees and/or feet (any joint site); the corresponding estimates for women were 1.9%, 9.0%, 23.7%, and 34.5%, respectively. The prevalence of generalised morning stiffness was 4.9% for men and 10.4% for women. The age adjusted odds ratios for locomotor disability in men ranged from 2.4 of pain at one joint site to 8.8 of pain at all three joint sites; for women these odds ratios varied between 2.5 and 5.7, respectively. The age adjusted odds ratios of generalised morning stiffness were 8.0 for men and 7.3 for women. CONCLUSION--There is a strong and independent association between locomotor disability and age, joint pain, and generalised morning stiffness in people aged 55 years and over. The odds for locomotor disability increase onefold for every year increase in age, while the presence of generalised morning stiffness is of greater influence than the presence of joint pain. PMID:7495342

  2. Determination of the Spontaneous Locomotor Activity in Drosophila melanogaster

    PubMed Central

    Woods, Jared K.; Kowalski, Suzanne; Rogina, Blanka

    2014-01-01

    Drosophila melanogaster has been used as an excellent model organism to study environmental and genetic manipulations that affect behavior. One such behavior is spontaneous locomotor activity. Here we describe our protocol that utilizes Drosophila population monitors and a tracking system that allows continuous monitoring of the spontaneous locomotor activity of flies for several days at a time. This method is simple, reliable, and objective and can be used to examine the effects of aging, sex, changes in caloric content of food, addition of drugs, or genetic manipulations that mimic human diseases. PMID:24747955

  3. Determination of the spontaneous locomotor activity in Drosophila melanogaster.

    PubMed

    Woods, Jared K; Kowalski, Suzanne; Rogina, Blanka

    2014-01-01

    Drosophila melanogaster has been used as an excellent model organism to study environmental and genetic manipulations that affect behavior. One such behavior is spontaneous locomotor activity. Here we describe our protocol that utilizes Drosophila population monitors and a tracking system that allows continuous monitoring of the spontaneous locomotor activity of flies for several days at a time. This method is simple, reliable, and objective and can be used to examine the effects of aging, sex, changes in caloric content of food, addition of drugs, or genetic manipulations that mimic human diseases. PMID:24747955

  4. Genotypic structure of a Drosophila population for adult locomotor activity

    SciTech Connect

    Grechanyi, G.V.; Korzun, V.M.

    1995-01-01

    Analysis of the variation of adult locomotor activity in four samples taken at different times from a natural population of Drosophila melanogaster showed that the total variation of this trait is relatively stable in time and has a substantial genetic component. Genotypic structure of the population for locomotor activity is characterized by the presence of large groups of genotypes with high and low values of this trait. A possible explanation for the presence of such groups in a population is cyclic density-dependent selection.

  5. Diphenyl Diselenide Protects Against Mortality, Locomotor Deficits and Oxidative Stress in Drosophila melanogaster Model of Manganese-Induced Neurotoxicity.

    PubMed

    Adedara, Isaac A; Abolaji, Amos O; Rocha, Joao B T; Farombi, Ebenezer O

    2016-06-01

    Several experimental and epidemiological reports have associated manganese exposure with induction of oxidative stress and locomotor dysfunctions. Diphenyl diselenide (DPDS) is widely reported to exhibit antioxidant, anti-inflammatory and neuroprotective effects in in vitro and in vivo studies via multiple biochemical mechanisms. The present study investigated the protective effect of DPDS on manganese-induced toxicity in Drosophila melanogaster. The flies were exposed, in a dietary regimen, to manganese alone (30 mmol per kg) or in combination with DPDS (10 and 20 µmol per kg) for 7 consecutive days. Exposure to manganese significantly (p < 0.05) increased flies mortality, whereas the survivors exhibited significant locomotor deficits with increased acetylcholinesterase (AChE) activity. However, dietary supplementation with DPDS caused a significant decrease in mortality, improvement in locomotor activity and restoration of AChE activity in manganese-exposed flies. Additionally, the significant decreases in the total thiol level, activities of catalase and glutathione-S-transferase were accompanied with significant increases in the generation of reactive oxygen and nitrogen species and thiobarbituric acid reactive substances in flies exposed to manganese alone. Dietary supplementation with DPDS significantly augmented the antioxidant status and prevented manganese-induced oxidative stress in the treated flies. Collectively, the present data highlight that DPDS may be a promising chemopreventive drug candidate against neurotoxicity resulting from acute manganese exposure. PMID:26875733

  6. The dopamine uptake inhibitor 3 alpha-[bis(4'-fluorophenyl)metoxy]-tropane reduces cocaine-induced early-gene expression, locomotor activity, and conditioned reward.

    PubMed

    Velázquez-Sánchez, Clara; Ferragud, Antonio; Hernández-Rabaza, Vicente; Nácher, Amparo; Merino, Virginia; Cardá, Miguel; Murga, Juan; Canales, Juan J

    2009-11-01

    Benztropine (BZT) analogs, a family of high-affinity dopamine transporter ligands, are molecules that exhibit pharmacological and behavioral characteristics predictive of significant therapeutic potential in cocaine addiction. Here, we examined in mice the effects of 3 alpha-[bis(4'-fluorophenyl)metoxy]-tropane (AHN-1055) on motor activity, conditioned place preference (CPP) and c-Fos expression in the striatum. AHN-1055 produced mild attenuation of spontaneous locomotor activity at a low dose (1 mg/kg) and weak stimulation at a higher dose (10 mg/kg). In parallel, the BZT analog significantly increased c-Fos expression in the dorsolateral caudoputamen at the high dose, whereas producing marginal decreases at low and moderate doses (1, 3 mg/kg) in both dorsal and ventral striatum. Interaction assays showed that cocaine's ability to stimulate locomotor activity was decreased by AHN-1055 treatment, but not by treatment with D-amphetamine. Such reduced ability did not result from an increase in stereotyped behavior. Another dopamine uptake inhibitor, nomifensine, decreased cocaine-induced locomotor activity but evoked by itself intense motor stereotypies. Remarkably, the BZT analog dose-dependently blocked cocaine-induced CPP without producing CPP when given alone, and blocked in conditioned mice cocaine-stimulated early-gene activation in the nucleus accumbens and dorsomedial striatum. These observations provide evidence that AHN-1055 does not behave as a classical psychomotor stimulant and that some of its properties, including attenuation of cocaine-induced striatal c-Fos expression, locomotor stimulation, and CPP, support its candidacy, and that of structurally related molecules, as possible pharmacotherapies in cocaine addiction. PMID:19606084

  7. Treating parents with attention-deficit/hyperactivity disorder: the effects of behavioral parent training and acute stimulant medication treatment on parent-child interactions.

    PubMed

    Babinski, Dara E; Waxmonsky, James G; Pelham, William E

    2014-10-01

    This multiple baseline study evaluated the efficacy of behavioral parent training (BPT) for 12 parents (M age = 39.17 years; 91% mothers) and their children (ages 6-12; 83% boys) both with Attention-Deficit/Hyperactivity Disorder (ADHD), and also explored the acute effect of stimulant medication for parents before and after BPT. Parents rated their own and their children's symptoms and impairment and were stabilized on optimally dosed medication. Then, parents discontinued medication and were randomly assigned to a 3, 4, or 5 week baseline (BL), during which they provided twice-weekly ratings of their impairment, parenting, and their child's behavior. Following BL, parents and their children completed two laboratory tasks, once on their optimally dosed medication and once on a placebo to assess observable effects of medication on parent-child behavior, and they completed additional assessments of family functioning. Parents then completed eight BPT sessions, during which they were unmedicated. Twice-weekly ratings of parent and child behavior were collected during BPT and additional ratings were collected upon completing BPT. Two more parent-child tasks with and without parent medication were conducted upon BPT completion to assess the observable effects of BPT and BPT plus medication. Ten (83.33%) parents completed the trial. Improvements in parent and child behavior were observed, and parents reported improved child behavior with BPT. Few benefits of BPT emerged through parent reports of parent functioning, with the exception of inconsistent discipline, and no medication or interaction effects emerged. These results, although preliminary, suggest that some parents with ADHD benefit from BPT. While pharmacological treatment is the most common intervention for adults with ADHD, further examination of psychosocial treatments for adults is needed. PMID:24687848

  8. Inflammation-mediating cytokine response to acute handcycling exercise with/without functional electrical stimulation-evoked lower-limb cycling.

    PubMed

    Paulson, Thomas A W; Bishop, Nicolette C; Smith, Brett M; Goosey-Tolfrey, Victoria L

    2014-01-01

    This feasibility study compared the plasma inflammation-mediating cytokine response to an acute bout of handcycling (HC) with and without the addition of functional electrical stimulation (FES)-evoked lower-limb cycling. On two separate occasions, five recreationally active, community-based participants with motor complete paraplegia (thoracic 5- 7) performed 30 min HC and hybrid exercise (HYB) at a fixed power output. Venous blood samples were collected at rest, immediately postexercise, 1 h postexercise (post+1) and 2 h postexercise (post+2). Plasma interleukin (IL)-6, IL-10, IL-1 receptor antagonist (IL-1ra), adrenaline, and cortisol concentrations were determined via enzyme-linked immunoassay. Plasma IL-6 concentrations were significantly (p < 0.04) elevated (~2.5-fold) at post+1 and post+2 in HYB only. A small (0.5-fold), nonsignificant (p > 0.05) increase in IL-6 was observed at post+1 in HC, with concentrations significantly higher in HYB at post+2 (p < 0.02). Plasma IL-1ra was unaffected in both trials. Although not reaching statistical significance (p = 0.15), a ~1-fold increase in IL-10 concentration was seen in HYB at post+2. In contrast, increases in adrenaline (p < 0.04) and cortisol (p = 0.08) were observed immediately postexercise in HC and HYB. Initial findings suggest paralyzed skeletal muscle releases IL-6 in response to FES-evoked contractions. HYB may provide a greater anti-inflammatory potential in individuals with a thoracic spinal cord injury compared with HC alone. PMID:25144177

  9. Feeding common carp Cyprinus carpio with β-glucan supplemented diet stimulates C-reactive protein and complement immune acute phase responses following PAMPs injection.

    PubMed

    Pionnier, Nicolas; Falco, Alberto; Miest, Joanna J; Shrive, Annette K; Hoole, Dave

    2014-08-01

    The effect of β-glucan as a feed additive on the serum and gene profile of C-reactive protein (CRP) and complement acute phase responses was ascertained in common carp Cyprinus carpio. In addition effects of subsequent intraperitoneal injections of pathogen-associated molecular patterns (PAMPs), i.e. LPS or poly(I:C), to mimic bacterial or viral infection respectively, were studied. Carp were first orally fed with β-glucan (MacroGard®) with a daily β-glucan intake of 6 mg per kg body weight or with control food for 25 days and then injected with PBS containing either LPS (4 mg/kg) or poly(I:C) (5 mg/kg) or PBS alone. Fish were sampled during the 25 days of the feeding period and up to 7 days post-PAMPs injections for serum and liver, head kidney and mid-gut tissues. Oral administration of β-glucan for 25 days significantly increased serum CRP levels and alternative complement activity (ACP). In addition, the subsequent LPS and poly(I:C) challenges significantly affected CRP and complement related gene expression profiles (crp1, crp2, c1r/s, bf/c2, c3 and masp2), with the greatest effects observed in the β-glucan fed fish. However, in fish fed β-glucan the PAMPs injections had less effects on CRP levels and complement activity in the serum than in control fed fish, suggesting that the 25 days of β-glucan immunostimulation was sufficient enough to reduce the effects of LPS and poly(I:C) injections. Results suggest that MacroGard® stimulated CRP and complement responses to PAMPs immunological challenges in common carp thus highlighting the beneficial β-glucan immunostimulant properties. PMID:24830773

  10. Comprehensive Locomotor Outcomes Correlate to Hyperacute Diffusion Tensor Measures After Spinal Cord Injury in the Adult Rat

    PubMed Central

    Kim, Joong; Song, Sheng-Kwei; Burke, Darlene A.; Magnuson, David S. K.

    2012-01-01

    In adult rats, locomotor deficits following a contusive thoracic spinal cord injury (SCI) are caused primarily by white matter loss/dysfunction at the epicenter. This loss/dysfunction decreases descending input from the brain and cervical spinal cord, and decreases ascending signals in long propriospinal, spinocerebellar and somatosensory pathways, among many others. Predicting the long-term functional consequences of a contusive injury acutely, without knowledge of the injury severity is difficult due to the temporary flaccid paralysis and loss of reflexes that accompanies spinal shock. It is now well known that recovery of high quality hindlimb stepping requires only 12-15% spared white matter at the epicenter, but that forelimb-hindlimb coordination and precision stepping (grid or horizontal ladder) requires substantially more trans-contusion communication. In order to translate our understanding of the neural substrates for functional recovery in the rat to the clinical arena, common outcome measures and imaging modalities are required. In the current study we furthered the exploration of one of these approaches, diffusion tensor magnetic resonance imaging (DTI), a technique now used commonly to image the brain in clinical research but rarely used diagnostically or prognostically for spinal cord injury. In the adult rat model of SCI, we found that hyper-acute (<3 hours post-injury) DTI of the lateral and ventral white matter at the injury epicenter was predictive of both electrophysiological and behavioral (locomotor) recovery at 4 weeks post-injury, despite the presence of flaccid paralysis/spinal shock. Regions of white matter with a minimum axial diffusivity of 1.5μm2/ms at 3 hours were able to conduct action potentials at 4 weeks, and axial diffusivity within the lateral funiculus was highly predictive of locomotor function at 4 weeks. These observations suggest that acute DTI should be useful to provide functional predictions for spared white matter

  11. Waved-1 mutant mice are hypersensitive to the locomotor actions of cocaine.

    PubMed

    Stanwood, Gregg D; Levitt, Pat

    2007-04-01

    Transforming growth factor-alpha (TGFalpha) is a well-known regulator of many developmental processes, and is expressed heavily in basal forebrain and striatal regions. When TGFalpha is reduced in Waved-1 (Wa-1) mutant mice, brain anatomy, biogenic amines, stress response, and behavior are normal prior to, but altered following puberty. As an initial screen for possible alterations in nigrostriatal and mesolimbic dopamine (DA) systems, we tested adult Wa-1 mutant mice in an open field, following acute injection with cocaine (15 mg/kg). Wa-1 mice exhibited significantly greater ambulatory distance, number of ambulatory episodes, and cocaine-induced motor stereotypies than do controls. These data indicate that adult Wa-1 mice are hypersensitive to the locomotor effects of cocaine and provide a new potential link between neurodevelopmental processes and adult psychostimulant responsiveness. PMID:17230552

  12. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

    SciTech Connect

    Thanos, P.K.; Thanos, P.K.; Bermeo, C.; Rubinstein, M.; Suchland, K.L.; Wang, G.-J.; Grandy, D.K.; Volkow, N.D.

    2010-05-01

    Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs

  13. Adenosinergic regulation of binge-like ethanol drinking and associated locomotor effects in male C57BL/6J mice

    PubMed Central

    Fritz, Brandon M; Boehm, Stephen L

    2015-01-01

    We recently observed that the addition of caffeine (a nonselective adenosine receptor antagonist) to a 20% ethanol solution significantly altered the intoxication profile of male C57BL/6J (B6) mice induced by voluntary binge-like consumption in the ‘Drinking-in-the-Dark’ (DID) paradigm. In the current study, the roles of A1 and A2A adenosine receptor subtypes, specifically, in binge-like ethanol consumption and associated locomotor effects were explored. Adult male B6 mice (PND 60-70) were allowed to consume 20% ethanol (v/v) or 2% sucrose (w/v) for 6 days via DID. On day 7, mice received a systemic administration (i.p.) of the A1 antagonist DPCPX (1, 3, 6 mg/kg), the A2A antagonist MSX-3 (1, 2, 4 mg/kg), or vehicle immediately prior to fluid access in DID. Antagonism of the A1 receptor via DPCPX was found to dose-dependently decrease binge-like ethanol intake and associated blood ethanol concentrations (p’s < 0.05), although no effect was observed on sucrose intake. Antagonism of A2A had no effect on ethanol or sucrose consumption, however, MSX-3 elicited robust locomotor stimulation in mice consuming either solution (p’s < 0.05). Together, these findings suggest unique roles for the A1 and A2A adenosine receptor subtypes in binge-like ethanol intake and its associated locomotor effects. PMID:26033424

  14. Rapid Sensitization of Physiological, Neuronal, and Locomotor Effects of Nicotine: Critical Role of Peripheral Drug Actions

    PubMed Central

    Lenoir, Magalie; Tang, Jeremy S.; Woods, Amina S.

    2013-01-01

    Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotinePM, 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotinePM injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization. PMID:23761889

  15. Effects of μ-Opioid Receptor Agonists in Assays of Acute Pain-Stimulated and Pain-Depressed Behavior in Male Rats: Role of μ-Agonist Efficacy and Noxious Stimulus Intensity

    PubMed Central

    Rice, Kenner C.; Negus, S. Stevens

    2015-01-01

    Pain is associated with stimulation of some behaviors and depression of others, and μ-opioid receptor agonists are among the most widely used analgesics. This study used parallel assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats to compare antinociception profiles for six μ-agonists that varied in efficacy at μ-opioid receptors (from highest to lowest: methadone, fentanyl, morphine, hydrocodone, buprenorphine, and nalbuphine). Intraperitoneal injection of diluted lactic acid served as an acute noxious stimulus to either stimulate stretching or depress operant responding maintained by electrical stimulation in an intracranial self-stimulation (ICSS). All μ-agonists blocked both stimulation of stretching and depression of ICSS produced by 1.8% lactic acid. The high-efficacy agonists methadone and fentanyl were more potent at blocking acid-induced depression of ICSS than acid-stimulated stretching, whereas lower-efficacy agonists displayed similar potency across assays. All μ-agonists except morphine also facilitated ICSS in the absence of the noxious stimulus at doses similar to those that blocked acid-induced depression of ICSS. The potency of the low-efficacy μ-agonist nalbuphine, but not the high-efficacy μ-agonist methadone, to block acid-induced depression of ICSS was significantly reduced by increasing the intensity of the noxious stimulus to 5.6% acid. These results demonstrate sensitivity of acid-induced depression of ICSS to a range of clinically effective μ-opioid analgesics and reveal distinctions between opioids based on efficacy at the μ-receptor. These results also support the use of parallel assays of pain-stimulated and -depressed behaviors to evaluate analgesic efficacy of candidate drugs. PMID:25406170

  16. Effects of caffeine and L-phenylisopropyladenosine on locomotor activity of mice

    SciTech Connect

    Buckholtz, N.S.; Middaugh, L.D.

    1987-10-01

    C57BL/6J and DBA/2J mice were used to determine if possible differences in the behavioral response to caffeine might be related to differences in A1 adenosine receptors. Caffeine stimulated locomotor activity of both strains, but the dose-response relationship and time course of drug action differed according to strain. Although their response to caffeine differed, the strains did not differ in response to the A1 adenosine agonist L-phenylisopropyladenosine (PIA) nor in the binding of the A1 agonist (/sup 3/H)N6-cyclohexyladenosine (CHA) in various brain regions. Thus, the behavioral differences in response to caffeine could not be accounted for by differences in adenosine binding. Of alternative mechanisms, strain differences in A2 receptors appear to be the most promising.

  17. DRUG EFFECTS ON THE LOCOMOTOR ACTIVITY OF LARVAL ZEBRAFISH.

    EPA Science Inventory

    As part of an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae and the effects of prototype drugs. Zebrafish larvae (6-7 days post-fertilization) were indiv...

  18. Active Gaze, Visual Look-Ahead, and Locomotor Control

    ERIC Educational Resources Information Center

    Wilkie, Richard M.; Wann, John P.; Allison, Robert S.

    2008-01-01

    The authors examined observers steering through a series of obstacles to determine the role of active gaze in shaping locomotor trajectories. Participants sat on a bicycle trainer integrated with a large field-of-view simulator and steered through a series of slalom gates. Steering behavior was determined by examining the passing distance through…

  19. A Model of Locomotor-Respiratory Coupling in Quadrupeds

    ERIC Educational Resources Information Center

    Giuliodori,, Mauricio J.; Lujan, Heidi L.; Briggs, Whitney S.; DiCarlo, Stephen E.

    2009-01-01

    Locomotion and respiration are not independent phenomena in running mammals because locomotion and respiration both rely on cyclic movements of the ribs, sternum, and associated musculature. Thus, constraints are imposed on locomotor and respiratory function by virtue of their linkage. Specifically, locomotion imposes mechanical constraints on…

  20. Locomotor Experience and Use of Social Information Are Posture Specific

    ERIC Educational Resources Information Center

    Adolph, Karen E.; Tamis-LeMonda, Catherine S.; Ishak, Shaziela; Karasik, Lana B.; Lobo, Sharon A.

    2008-01-01

    The authors examined the effects of locomotor experience on infants' perceptual judgments in a potentially risky situation--descending steep and shallow slopes--while manipulating social incentives to determine where perceptual judgments are most malleable. Twelve-month-old experienced crawlers and novice walkers were tested on an adjustable…

  1. Anxiolytic-like, stimulant and neuroprotective effects of Ilex paraguariensis extracts in mice.

    PubMed

    Santos, E C S; Bicca, M A; Blum-Silva, C H; Costa, A P R; Dos Santos, A A; Schenkel, E P; Farina, M; Reginatto, F H; de Lima, T C M

    2015-04-30

    Yerba-mate (Ilex paraguariensis St. Hil.) is the most used beverage in Latin America with approximately 426 thousand of tons consumed per year. Considering the broad use of this plant, we aimed to investigate the anxiety-like and stimulant activity of both the hydroethanolic (HE) and aqueous (AE) extracts from leaves of I. paraguariensis. Swiss mice were treated with I. paraguariensis HE or AE chronically or acutely, respectively, followed by evaluation in the elevated plus-maze (EPM; anxiety-like paradigm), open field (OF; locomotor activity) or the step-down avoidance task (memory assessment). Following behavioral protocols the brains were collected for evaluation of acetylcholinesterase (AChE) activity ex vivo. Chronic treatment with HE induced an anxiolytic-like effect and increased motor activity besides augmented AChE activity. Additionally, acute treatment with AE prevented the scopolamine-induced memory deficit in the step-down avoidance task. Overall, our results indicate the importance of the I. paraguariensis-induced CNS effects, since it is a widely used nutraceutical. We have reported anxiolytic, stimulant and neuroprotective effects for this plant species. These effects are potentially modulated by the cholinergic system as well as by caffeine. PMID:25681522

  2. Anatomical Location of the Mesencephalic Locomotor Region and Its Possible Role in Locomotion, Posture, Cataplexy, and Parkinsonism

    PubMed Central

    Sherman, David; Fuller, Patrick M.; Marcus, Jacob; Yu, Jun; Zhang, Ping; Chamberlin, Nancy L.; Saper, Clifford B.; Lu, Jun

    2015-01-01

    The mesencephalic (or midbrain) locomotor region (MLR) was first described in 1966 by Shik and colleagues, who demonstrated that electrical stimulation of this region induced locomotion in decerebrate (intercollicular transection) cats. The pedunculopontine tegmental nucleus (PPT) cholinergic neurons and midbrain extrapyramidal area (MEA) have been suggested to form the neuroanatomical basis for the MLR, but direct evidence for the role of these structures in locomotor behavior has been lacking. Here, we tested the hypothesis that the MLR is composed of non-cholinergic spinally projecting cells in the lateral pontine tegmentum. Our results showed that putative MLR neurons medial to the PPT and MEA in rats were non-cholinergic, glutamatergic, and express the orexin (hypocretin) type 2 receptors. Fos mapping correlated with motor behaviors revealed that the dorsal and ventral MLR are activated, respectively, in association with locomotion and an erect posture. Consistent with these findings, chemical stimulation of the dorsal MLR produced locomotion, whereas stimulation of the ventral MLR caused standing. Lesions of the MLR (dorsal and ventral regions together) resulted in cataplexy and episodic immobility of gait. Finally, trans-neuronal tracing with pseudorabies virus demonstrated disynaptic input to the MLR from the substantia nigra via the MEA. These findings offer a new perspective on the neuroanatomic basis of the MLR, and suggest that MLR dysfunction may contribute to the postural and gait abnormalities in Parkinsonism. PMID:26157418

  3. Effects of caffeine on locomotor activity of horses: determination of the no-effect threshold.

    PubMed

    Queiroz-Neto, A; Zamur, G; Carregaro, A B; Mataqueiro, M I; Salvadori, M C; Azevedo, C P; Harkins, J D; Tobin, T

    2001-01-01

    Caffeine is the legal stimulant consumed most extensively by the human world population and may be found eventually in the urine and/or blood of race horses. The fact that caffeine is in foods led us to determine the highest no-effect dose (HNED) of caffeine on the spontaneous locomotor activity of horses and then to quantify this substance in urine until it disappeared. We built two behavioural stalls equipped with juxtaposed photoelectric sensors that emit infrared beams that divide the stall into nine sectors in a 'tic-tac-toe' fashion. Each time a beam was interrupted by a leg of the horse, a pulse was generated; the pulses were counted at 5-min intervals and stored by a microcomputer. Environmental effects were minimized by installing exhaust fans producing white noise that obscured outside sounds. One-way observation windows prevented the animals from seeing outside. The sensors were turned on 45 min before drug administration (saline control or caffeine). The animals were observed for up to 8 h after i.v. administration of 2.0, 2.5, 3.0 or 5.0 mg caffeine kg(-1). The HNED of caffeine for stimulation of the spontaneous locomotor activity of horses was 2.0 mg kg(-1). The quantification of caffeine in urine and plasma samples was done by gradient HPLC with UV detection. The no-effect threshold should not be greater than 2.0 microg caffeine ml(-1) plasma or 5.0 microg caffeine ml(-1) urine. PMID:11404835

  4. Activation of neurotensin receptor type 1 attenuates locomotor activity.

    PubMed

    Vadnie, Chelsea A; Hinton, David J; Choi, Sun; Choi, YuBin; Ruby, Christina L; Oliveros, Alfredo; Prieto, Miguel L; Park, Jun Hyun; Choi, Doo-Sup

    2014-10-01

    Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF-81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. PMID:24929110

  5. The Nicotine-Evoked Locomotor Response: A Behavioral Paradigm for Toxicity Screening in Zebrafish (Danio rerio) Embryos and Eleutheroembryos Exposed to Methylmercury

    PubMed Central

    Mora-Zamorano, Francisco X.; Svoboda, Kurt R.; Carvan, Michael J.

    2016-01-01

    This study is an adaptation of the nicotine-evoked locomotor response (NLR) assay, which was originally utilized for phenotype-based neurotoxicity screening in zebrafish embryos. Zebrafish embryos do not exhibit spontaneous swimming until roughly 4 days post-fertilization (dpf), however, a robust swimming response can be induced as early as 36 hours post-fertilization (hpf) by means of acute nicotine exposure (30–240μM). Here, the NLR was tested as a tool for early detection of locomotor phenotypes in 36, 48 and 72 hpf mutant zebrafish embryos of the non-touch-responsive maco strain; this assay successfully discriminated mutant embryos from their non-mutant siblings. Then, methylmercury (MeHg) was used as a proof-of-concept neurotoxicant to test the effectiveness of the NLR assay as a screening tool in toxicology. The locomotor effects of MeHg were evaluated in 6 dpf wild type eleutheroembryos exposed to waterborne MeHg (0, 0.01, 0.03 and 0.1μM). Afterwards, the NLR assay was tested in 48 hpf embryos subjected to the same MeHg exposure regimes. Embryos exposed to 0.01 and 0.03μM of MeHg exhibited significant increases in locomotion in both scenarios. These findings suggest that similar locomotor phenotypes observed in free swimming fish can be detected as early as 48 hpf, when locomotion is induced with nicotine. PMID:27123921

  6. Inducible Nitric Oxide Inhibitors Block NMDA Antagonist-Stimulated Motoric Behaviors and Medial Prefrontal Cortical Glutamate Efflux

    PubMed Central

    Bergstrom, Hadley C.; Darvesh, Altaf S.; Berger, S. P.

    2015-01-01

    Nitric oxide (NO) plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA)-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS) for studying the neurobehavioral effects of non-competitive NMDA-antagonist stimulants such as dizocilpine (MK-801) and phencyclidine (PCP). This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS) aminoguanidine (AG) and (-)-epigallocatechin-3-gallate (EGCG) in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG, or vehicle prior to receiving NMDA antagonists MK-801, PCP, or a conventional psychostimulant (cocaine) and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex (mPFC) was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated mPFC glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in “green tea” and chocolate) may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia. PMID:26696891

  7. The dorsomedial shell of the nucleus accumbens facilitates cocaine-induced locomotor activity during the induction of behavioral sensitization.

    PubMed

    Todtenkopf, M S; Carreiras, T; Melloni, R H; Stellar, J R

    2002-04-01

    The mesolimbic dopamine system has been intensely studied as the neural circuit mediating the locomotor response to psychostimulants and behavioral sensitization. In particular, the dopaminergic innervation of the nucleus accumbens has been implicated as a site responsible for the manifestations of behavioral sensitization. Previous studies have demonstrated an augmented release of dopamine in the nucleus accumbens upon a systemic injection of a psychostimulant. In addition, alterations in the dopaminergic innervation patterns in this brain region have been demonstrated in animals that received repeated injections of cocaine. Furthermore, lesions of projection sites that have terminations in the nucleus accumbens have demonstrated alterations in psychostimulant induced locomotion, both acutely, as well as in sensitization paradigms. Since dopamine in the nucleus accumbens is believed to regulate several excitatory amino acid inputs, the present study examined the effects of a localized electrolytic lesion in the dorsomedial shell of the nucleus accumbens in order to better understand the functional role this brain region has in behavioral sensitization. All animals received bi-daily injections of 15 mg/kg i.p. cocaine. Only those demonstrating behavioral sensitization after a subsequent challenge dose were included in the analysis. Following acute exposure to cocaine, lesioned animals did not show any difference in their locomotor response when compared with sham controls. However, after repeated exposure to cocaine, sensitized animals demonstrated a significant attenuation in locomotor behavior when compared with sensitized sham controls. This decrease in horizontal locomotion persisted 2 days into withdrawal, yet dissipated in the sensitized animals that were challenged 2 weeks following their last injection. The data presented here demonstrate that the dorsomedial shell of the nucleus accumbens plays an important role in the initial stages of behavioral

  8. Locomotor Dysfunction after Long-duration Space Flight and Development of Countermeasures to Facilitate Faster Recovery

    NASA Astrophysics Data System (ADS)

    Mulavara, Ajitkumar; Wood, Scott; Cohen, Helen; Bloomberg, Jacob

    2012-07-01

    movement control and a functional mobility test to investigate overall functional locomotor ability. Postflight sessions were given on days 1, 2, 4, 7 after their return. Subjects walked on a treadmill driven at 1.8 m/s while performing a visual task. Motion data from head and trunk segmental motion data were obtained to calculate the angular head pitch (HP) movements during walking trials while subjects performed the visual task, to estimate the contributions of vestibular reflexive mechanisms in HP movements. Astronauts showed a heterogeneous response pattern of both increases and decreases in the amplitude of HP movement. We investigated the underlying mechanisms of this heterogeneity in postflight responses in head movement control by examining data obtained using the same experimental test paradigm on a vestibular clinical population (VC) and in normal subjects undergoing adaptation to acute body load support unloading. Results showed that exposure to unloaded locomotion caused a significant increase in HP movements, whereas in the VC patients the HP movements were significantly decreased. We infer that BLS-mediated somatosensory input centrally modulates vestibular input and can adaptively modify head-movement control during locomotion. Thus, space flight may cause a central adaptation of the converging vestibular and body load-sensing somatosensory systems. To investigate changes in functional mobility astronaut subjects walked at their preferred pace around an obstacle course consisting of several pylons and obstacles set up on a foam floor, which provided an unstable walking surface. Subjects were instructed to walk around the course as fast as possible without touching any of the objects on the course for a total of six individual trials per test session. One of the dependent measures was time to complete the course (TCC, sec). The learning rate over the six trials performed on preflight and the first day after landing (micro curve) was used to characterize the

  9. The expression of methiopropamine-induced locomotor sensitization requires dopamine D2, but not D1, receptor activation in the rat.

    PubMed

    Yoon, Hyung Shin; Cai, Wen Ting; Lee, Young Hun; Park, Kyung Tae; Lee, Yong Sup; Kim, Jeong-Hoon

    2016-09-15

    Methiopropamine (MPA) is a structural analog to methamphetamine and is categorized as a novel psychoactive substance that needs to be controlled. However, no study has been performed to determine whether MPA actually develops an addiction-like behavior similar to those arising from other psychomotor stimulants. Thus, we attempted to determine whether MPA produces locomotor sensitization in a manner similar to amphetamine. In the first experiment, rats were pre-exposed to either saline or one of three different doses of MPA (0.2, 1.0, or 5.0mg/kg, IP) with a total of four injections, respectively. After a 2-week withdrawal period, when they were challenged with the same dose of MPA, only the group that was pre-exposed to high dose of MPA (5.0mg/kg) showed sensitized locomotor activity. In the second experiment, all rats were pre-exposed to MPA (5.0mg/kg) only. Interestingly, the expression of MPA-induced locomotor sensitization was inhibited by a pre-injection of a dopamine D2 receptor antagonist, eticlopride (0.05mg/kg, IP), though not by a dopamine D1 receptor antagonist, SCH23390 (0.01mg/kg, IP). These results suggest that repeated injection of MPA in the rat provokes certain neuronal changes involving specific, likely D2, dopamine receptor-mediated pathways that contribute to the expression of MPA-induced locomotor sensitization. PMID:27265782

  10. Establishment of a novel experimental protocol for drug-induced seizure liability screening based on a locomotor activity assay in zebrafish.

    PubMed

    Koseki, Naoteru; Deguchi, Jiro; Yamashita, Akihito; Miyawaki, Izuru; Funabashi, Hitoshi

    2014-08-01

    As drug-induced seizures have severe impact on drug development, evaluating seizure induction potential of candidate drugs at the early stages of drug discovery is important. A novel assay system using zebrafish has attracted interest as a high throughput toxicological in vivo assay system, and we tried to establish an experimental method for drug-induced seizure liability on the basis of locomotor activity in zebrafish. We monitored locomotor activity at high-speed movement (> 20 mm/sec) for 60 min immediately after exposure, and assessed seizure liability potential in some drugs using locomotor activity. However this experimental procedure was not sufficient for predicting seizures because the potential of several drugs with demonstrated seizure potential in mammals was not detected. We, therefore, added other parameters for locomotor activity such as extending exposure time or conducting flashlight stimulation (10 Hz) which is a known seizure induction stimulus, and these additional parameters improved seizure potential detection in some drugs. The validation study using the improved methodology was used to assess 52 commercially available drugs, and the prediction rate was approximately 70%. The experimental protocol established in this present study is considered useful for seizure potential screening during early stages of drug discovery. PMID:25056783

  11. Acute total sleep deprivation potentiates cocaine-induced hyperlocomotion in mice.

    PubMed

    Berro, L F; Santos, R; Hollais, A W; Wuo-Silva, R; Fukushiro, D F; Mári-Kawamoto, E; Costa, J M; Trombin, T F; Patti, C L; Grapiglia, S B; Tufik, S; Andersen, M L; Frussa-Filho, R

    2014-09-01

    Sleep deprivation is common place in modern society. Nowadays, people tend to self-impose less sleep in order to achieve professional or social goals. In the social context, late-night parties are frequently associated with higher availability of recreational drugs with abuse potential. Physiologically, all of these drugs induce an increase in dopamine release in the mesolimbic dopaminergic system, which leads to hyperlocomotion in rodents. Sleep deprivation also seems to play an important role in the events related to the neurotransmission of the dopaminergic system by potentiating its behavioral effects. In this scenario, the aim of the present study was to investigate the effects of total sleep deprivation (6h) on the acute cocaine-induced locomotor stimulation in male mice. Animals were sleep deprived or maintained in their home cages and subsequently treated with an acute i.p. injection of 15mg/kg cocaine or saline and observed in the open field. Total sleep deprivation for 6h potentiated the hyperlocomotion induced by acute cocaine administration. In addition, the cocaine sleep deprived group showed a decreased ratio central/total locomotion compared to the cocaine control group, which might be related to an increase in the impulsiveness of mice. Our data indicate that acute periods of sleep loss should be considered risk factors for cocaine abuse. PMID:25067829

  12. Acute and chronic hypoxia: implications for cerebral function and exercise tolerance

    PubMed Central

    Goodall, Stuart; Twomey, Rosie; Amann, Markus

    2015-01-01

    Purpose To outline how hypoxia profoundly affects neuronal functionality and thus compromise exercise-performance. Methods Investigations using electroencephalography (EEG) and transcranial magnetic stimulation (TMS) detecting neuronal changes at rest and those studying fatiguing effects on whole-body exercise performance in acute (AH) and chronic hypoxia (CH) were evaluated. Results At rest during very early hypoxia (<1-h), slowing of cerebral neuronal activity is evident despite no change in corticospinal excitability. As time in hypoxia progresses (3-h), increased corticospinal excitability becomes evident; however, changes in neuronal activity are unknown. Prolonged exposure (3–5 d) causes a respiratory alkalosis which modulates Na+ channels, potentially explaining reduced neuronal excitability. Locomotor exercise in AH exacerbates the development of peripheral-fatigue; as the severity of hypoxia increases, mechanisms of peripheral-fatigue become less dominant and CNS hypoxia becomes the predominant factor. The greatest central-fatigue in AH occurs when SaO2 is ≤75%, a level that coincides with increasing impairments in neuronal activity. CH does not improve the level of peripheral-fatigue observed in AH; however, it attenuates the development of central-fatigue paralleling increases in cerebral O2 availability and corticospinal excitability. Conclusions The attenuated development of central-fatigue in CH might explain, the improvements in locomotor exercise-performance commonly observed after acclimatisation to high altitude. PMID:25593787

  13. Development of a Countermeasure to Enhance Postflight Locomotor Adaptability

    NASA Technical Reports Server (NTRS)

    Bloomberg, Jacob J.

    2006-01-01

    Astronauts returning from space flight experience locomotor dysfunction following their return to Earth. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially learns to learn and therefore can reorganize more rapidly when faced with a novel adaptive challenge. We have previously confirmed that subjects participating in adaptive generalization training programs using a variety of visuomotor distortions can enhance their ability to adapt to a novel sensorimotor environment. Importantly, this increased adaptability was retained even one month after completion of the training period. Adaptive generalization has been observed in a variety of other tasks requiring sensorimotor transformations including manual control tasks and reaching (Bock et al., 2001, Seidler, 2003) and obstacle avoidance during walking (Lam and Dietz, 2004). Taken together, the evidence suggests that a training regimen exposing crewmembers to variation in locomotor conditions, with repeated transitions among states, may enhance their ability to learn how to reassemble appropriate locomotor patterns upon return from microgravity. We believe exposure to this type of training will extend crewmembers locomotor behavioral repertoires, facilitating the return of functional mobility after long duration space flight. Our proposed training protocol will compel subjects to develop new behavioral solutions under varying sensorimotor demands. Over time subjects will learn to create appropriate locomotor solution more rapidly enabling acquisition of mobility sooner after long-duration space flight. Our laboratory is currently developing adaptive generalization training procedures and the

  14. L-tetrahydropalmatine inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal activity and dopamine D3 receptor expression.

    PubMed

    Yun, Jaesuk

    2014-09-25

    Methamphetamine (METH) is a psychomotor stimulant that produces hyperlocomotion in rodents. l-tetrahydropalmatine (l-THP) is an active ingredient found in Corydalis ternata which has been used as a traditional herbal preparation in Asian countries for centuries, however, the effect of l-THP on METH-induced phenotypes largely unknown. In this study, to evaluate the effect of l-THP on METH-induced psychotropic effects, rats were pretreated with l-THP (10 and 15 mg/kg) before acute METH injection, following which the total distance the rats moved in an hour was measured. To clarify a possible mechanism underlying the effect of l-THP on METH-induced behavioral changes, dopamine receptor mRNA expression levels in the striatum of the rats was measured following the locomotor activity study. In addition, the effect of l-THP (10 and 15 mg/kg) on serotonergic (5-HTergic) neuronal pathway activation was studied by measurement of 5-HT (80 μg/10μl/mouse)-induced head twitch response (HTR) in mice. l-THP administration significantly inhibited both hyperlocomotion in rats and HTR in mice. l-THP inhibited climbing behavior-induced by dopaminergic (DAergic) neuronal activation in mice. Furthermore, l-THP attenuated the decrease in dopamine D3 receptor mRNA expression levels in the striatum of the rats induced by METH. These results suggest that l-THP can ameliorate behavioral phenotype induced by METH through regulation of 5-HT neuronal activity and dopamine D3 receptor expression. PMID:25172791

  15. Retinal Stimulation on Rabbit Using Complementary Metal Oxide Semiconductor Based Multichip Flexible Stimulator toward Retinal Prosthesis

    NASA Astrophysics Data System (ADS)

    Tokuda, Takashi; Asano, Ryosuke; Sugitani, Sachie; Taniyama, Mari; Terasawa, Yasuo; Nunoshita, Masahiro; Nakauchi, Kazuaki; Fujikado, Takashi; Tano, Yasuo; Ohta, Jun

    2008-04-01

    The Functionality of a complementary metal oxide semiconductor (CMOS) LSI-based, multichip flexible retinal stimulator was demonstrated in retinal stimulation experiments on rabbits. A 1×4-configured multichip stimulator was fabricated for application to experiments on animals. An experimental procedure including surgical operations was developed, and retinal stimulation was performed with the fabricated multichip stimulator. Neural responses on the visual cortex were successfully evoked by the fabricated stimulator. The stimulator is confirmed to be applicable to acute animal experiments.

  16. Stereoselective Effects of Abused "Bath Salt" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation.

    PubMed

    Gannon, Brenda M; Williamson, Adrian; Suzuki, Masaki; Rice, Kenner C; Fantegrossi, William E

    2016-03-01

    3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit "bath salts" products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(-)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(-)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(-)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(-)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(-)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse. PMID:26769917

  17. A Locomotor Deficit Induced by Sublethal Doses of Pyrethroid and Neonicotinoid Insecticides in the Honeybee Apis mellifera.

    PubMed

    Charreton, Mercédès; Decourtye, Axel; Henry, Mickaël; Rodet, Guy; Sandoz, Jean-Christophe; Charnet, Pierre; Collet, Claude

    2015-01-01

    The toxicity of pesticides used in agriculture towards non-targeted organisms and especially pollinators has recently drawn the attention from a broad scientific community. Increased honeybee mortality observed worldwide certainly contributes to this interest. The potential role of several neurotoxic insecticides in triggering or potentiating honeybee mortality was considered, in particular phenylpyrazoles and neonicotinoids, given that they are widely used and highly toxic for insects. Along with their ability to kill insects at lethal doses, they can compromise survival at sublethal doses by producing subtle deleterious effects. In this study, we compared the bee's locomotor ability, which is crucial for many tasks within the hive (e.g. cleaning brood cells, feeding larvae…), before and after an acute sublethal exposure to one insecticide belonging to the two insecticide classes, fipronil and thiamethoxam. Additionally, we examined the locomotor ability after exposure to pyrethroids, an older chemical insecticide class still widely used and known to be highly toxic to bees as well. Our study focused on young bees (day 1 after emergence) since (i) few studies are available on locomotion at this stage and (ii) in recent years, pesticides have been reported to accumulate in different hive matrices, where young bees undergo their early development. At sublethal doses (SLD48h, i.e. causing no mortality at 48 h), three pyrethroids, namely cypermethrin (2.5 ng/bee), tetramethrin (70 ng/bee), tau-fluvalinate (33 ng/bee) and the neonicotinoid thiamethoxam (3.8 ng/bee) caused a locomotor deficit in honeybees. While the SLD48h of fipronil (a phenylpyrazole, 0.5 ng/bee) had no measurable effect on locomotion, we observed high mortality several days after exposure, an effect that was not observed with the other insecticides. Although locomotor deficits observed in the sublethal range of pyrethroids and thiamethoxam would suggest deleterious effects in the field, the case of

  18. A Locomotor Deficit Induced by Sublethal Doses of Pyrethroid and Neonicotinoid Insecticides in the Honeybee Apis mellifera

    PubMed Central

    Charreton, Mercédès; Decourtye, Axel; Henry, Mickaël; Rodet, Guy; Sandoz, Jean-Christophe; Charnet, Pierre; Collet, Claude

    2015-01-01

    The toxicity of pesticides used in agriculture towards non-targeted organisms and especially pollinators has recently drawn the attention from a broad scientific community. Increased honeybee mortality observed worldwide certainly contributes to this interest. The potential role of several neurotoxic insecticides in triggering or potentiating honeybee mortality was considered, in particular phenylpyrazoles and neonicotinoids, given that they are widely used and highly toxic for insects. Along with their ability to kill insects at lethal doses, they can compromise survival at sublethal doses by producing subtle deleterious effects. In this study, we compared the bee’s locomotor ability, which is crucial for many tasks within the hive (e.g. cleaning brood cells, feeding larvae…), before and after an acute sublethal exposure to one insecticide belonging to the two insecticide classes, fipronil and thiamethoxam. Additionally, we examined the locomotor ability after exposure to pyrethroids, an older chemical insecticide class still widely used and known to be highly toxic to bees as well. Our study focused on young bees (day 1 after emergence) since (i) few studies are available on locomotion at this stage and (ii) in recent years, pesticides have been reported to accumulate in different hive matrices, where young bees undergo their early development. At sublethal doses (SLD48h, i.e. causing no mortality at 48h), three pyrethroids, namely cypermethrin (2.5 ng/bee), tetramethrin (70 ng/bee), tau-fluvalinate (33 ng/bee) and the neonicotinoid thiamethoxam (3.8 ng/bee) caused a locomotor deficit in honeybees. While the SLD48h of fipronil (a phenylpyrazole, 0.5 ng/bee) had no measurable effect on locomotion, we observed high mortality several days after exposure, an effect that was not observed with the other insecticides. Although locomotor deficits observed in the sublethal range of pyrethroids and thiamethoxam would suggest deleterious effects in the field, the case

  19. Nifedipine and flunarizine block amphetamine-induced behavioral stimulation in mice.

    PubMed

    Grebb, J A

    1986-06-30

    Sixteen calcium channel inhibitors (CCI's) were tested in a model utilizing amphetamine-induced behavioral stimulation in mice. Nifedipine, flunarizine and possibly PY 108-068 were effective in blocking amphetamine-induced locomotor stimulation. Verapamil, diltiazem and many other CCI's were ineffective in this experimental paradigm. PMID:3724362

  20. Force wave transmission through the human locomotor system.

    PubMed

    Voloshin, A; Wosk, J; Brull, M

    1981-02-01

    A method to measure the capability of the human shock absorber system to attenuate input dynamic loading during the gait is presented. The experiments were carried out with two groups: healthy subjects and subjects with various pathological conditions. The results of the experiments show a considerable difference in the capability of each group's shock absorbers to attenuate force transmitted through the locomotor system. Comparison shows that healthy subjects definitely possess a more efficient shock-absorbing capacity than do those subjects with joint disorders. Presented results show that degenerative changes in joints reduce their shock absorbing capacity, which leads to overloading of the next shock absorber in the locomotor system. So, the development of osteoarthritis may be expected to result from overloading of a shock absorber's functional capacity. PMID:7253613

  1. Multi-terrain locomotor interactions in flying snakes

    NASA Astrophysics Data System (ADS)

    Yeaton, Isaac; Baumgardner, Grant; Ross, Shane; Socha, John

    Arboreal snakes of the genus Chrysopelea are the only known snakes to glide. To execute aerial locomotion, a snake uses one of several stereotyped jumps from a tree into the air, while simultaneously flattening its body into an aerodynamically favorable shape. Large amplitude traveling waves are propagated posteriorly during the stable glide, while landing involves body wrapping, passive body compression, and energy absorption through compliance in the landing substrate to dissipate the accumulated kinetic energy from the glide. In all of these locomotor events, from interacting with cylindrical branches, falling through the air, grasping compliant tree branches and leaves, to landing on solid ground, snakes appropriate the same body morphology and perhaps the same basic neural mechanisms. Here we discuss our use of computational models and animal experiments to understand how flying snakes interact with and locomote on and through multiple media, potentially providing principles for legless locomotor designs. Supported by NSF 1351322.

  2. Effects of muscarinic M1 receptor blockade on cocaine-induced elevations of brain dopamine levels and locomotor behavior in rats.

    PubMed

    Tanda, Gianluigi; Ebbs, Aaron L; Kopajtic, Theresa A; Elias, Lyn M; Campbell, Bettye L; Newman, Amy H; Katz, Jonathan L

    2007-04-01

    Cholinergic muscarinic systems have been shown to influence dopaminergic function in the central nervous system. In addition, previous studies of benztropine analogs that inhibit dopamine uptake and show antagonism at muscarinic receptors show these drugs to be less effective than cocaine in producing its various prototypic effects such as locomotor stimulation. Because previous pharmacological studies on these topics have used nonselective M1 antagonists, we examined the interactions of preferential M1 muscarinic antagonists and cocaine. Dose-dependent increases in extracellular levels of dopamine in selected brain areas, the nucleus accumbens (NAc) shell and core, and the prefrontal cortex, were produced by cocaine but not by the preferential M1 antagonists telenzepine and trihexyphenidyl. When administered with cocaine, however, both M1 antagonists dose-dependently increased the effects of cocaine on dopamine in the NAc shell, and these effects were selective in that they were not obtained in the NAc core or in the prefrontal cortex. Telenzepine also increased locomotor activity, although the effect was small compared with that of cocaine. The locomotor stimulant effects of trihexyphenidyl, in contrast, approached those of cocaine. Telenzepine attenuated, whereas trihexyphenidyl enhanced the locomotor stimulant effects of cocaine, with neither drug facilitating cocaine-induced stereotypy. The present results indicate that preferential antagonist effects at muscarinic M1 receptors do not uniformly alter all of the effects of cocaine, nor do they explain the differences in effects of cocaine and benztropine analogs, and that the alterations in dopamine levels in the NAc shell do not predict the behavioral effects of the interactions with cocaine. PMID:17255465

  3. Gestational Toluene Exposure Effects on Spontaneous and Amphetamine-Induced Locomotor Behavior in Rats

    PubMed Central

    Mohammadi, Michael H.; Batis, Jeffery C.; Hannigan, John H.

    2007-01-01

    The abuse of volatile organic solvents (inhalants) continues to be a major health concern throughout the world. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. The neurobehavioral teratogenic sequelae of solvent abuse (i.e., repeated, brief inhalation exposures to very high concentrations of solvents) have not been examined thoroughly. In a preclinical model of inhalant abuse, timed-pregnant Sprague-Dawley rats were exposed to 0, 8,000, or 12,000 parts per million (ppm) for 15 min twice daily from gestation day 8 (GD8) through GD20. In the first experiment, separate groups of offspring were observed individually in an open-field on postnatal day 22 (PN22), PN42 or PN63. In the second experiment, other offspring given identical prenatal toluene exposures were observed in an “open-field” following an acute i.p. injection of amphetamine (0, 0.56, 1.78 mg/kg) on PN28. Automated measurements of distance traveled and ambulatory time were recorded. Prenatal toluene exposure resulted in small alterations in spontaneous activity compared to non-exposed rats. Prenatal exposure to 12,000 ppm toluene resulted in significant hyposensitivity to the locomotor stimulatory effects of the amphetamine challenge in male but not female rats on PN28. The results demonstrate that prenatal exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous and amphetamine-induced locomotor behavior in rats. The expression of these effects also appears to depend upon the postnatal age of testing. These results imply that abuse of organic solvents during pregnancy in humans may also produce long-lasting effects on biobehavioral development. PMID:17112700

  4. Vestibular lesion-induced developmental plasticity in spinal locomotor networks during Xenopus laevis metamorphosis.

    PubMed

    Beyeler, Anna; Rao, Guillaume; Ladepeche, Laurent; Jacques, André; Simmers, John; Le Ray, Didier

    2013-01-01

    During frog metamorphosis, the vestibular sensory system remains unchanged, while spinal motor networks undergo a massive restructuring associated with the transition from the larval to adult biomechanical system. We investigated in Xenopus laevis the impact of a pre- (tadpole stage) or post-metamorphosis (juvenile stage) unilateral labyrinthectomy (UL) on young adult swimming performance and underlying spinal locomotor circuitry. The acute disruptive effects on locomotion were similar in both tadpoles and juvenile frogs. However, animals that had metamorphosed with a preceding UL expressed restored swimming behavior at the juvenile stage, whereas animals lesioned after metamorphosis never recovered. Whilst kinematic and electrophysiological analyses of the propulsive system showed no significant differences in either juvenile group, a 3D biomechanical simulation suggested that an asymmetry in the dynamic control of posture during swimming could account for the behavioral restoration observed in animals that had been labyrinthectomized before metamorphosis. This hypothesis was subsequently supported by in vivo electromyography during free swimming and in vitro recordings from isolated brainstem/spinal cord preparations. Specifically, animals lesioned prior to metamorphosis at the larval stage exhibited an asymmetrical propulsion/posture coupling as a post-metamorphic young adult. This developmental alteration was accompanied by an ipsilesional decrease in propriospinal coordination that is normally established in strict left-right symmetry during metamorphosis in order to synchronize dorsal trunk muscle contractions with bilateral hindlimb extensions in the swimming adult. Our data thus suggest that a disequilibrium in descending vestibulospinal information during Xenopus metamorphosis leads to an altered assembly of adult spinal locomotor circuitry. This in turn enables an adaptive compensation for the dynamic postural asymmetry induced by the vestibular imbalance

  5. Vestibular Lesion-Induced Developmental Plasticity in Spinal Locomotor Networks during Xenopus laevis Metamorphosis

    PubMed Central

    Beyeler, Anna; Rao, Guillaume; Ladepeche, Laurent; Jacques, André; Simmers, John; Le Ray, Didier

    2013-01-01

    During frog metamorphosis, the vestibular sensory system remains unchanged, while spinal motor networks undergo a massive restructuring associated with the transition from the larval to adult biomechanical system. We investigated in Xenopus laevis the impact of a pre- (tadpole stage) or post-metamorphosis (juvenile stage) unilateral labyrinthectomy (UL) on young adult swimming performance and underlying spinal locomotor circuitry. The acute disruptive effects on locomotion were similar in both tadpoles and juvenile frogs. However, animals that had metamorphosed with a preceding UL expressed restored swimming behavior at the juvenile stage, whereas animals lesioned after metamorphosis never recovered. Whilst kinematic and electrophysiological analyses of the propulsive system showed no significant differences in either juvenile group, a 3D biomechanical simulation suggested that an asymmetry in the dynamic control of posture during swimming could account for the behavioral restoration observed in animals that had been labyrinthectomized before metamorphosis. This hypothesis was subsequently supported by in vivo electromyography during free swimming and in vitro recordings from isolated brainstem/spinal cord preparations. Specifically, animals lesioned prior to metamorphosis at the larval stage exhibited an asymmetrical propulsion/posture coupling as a post-metamorphic young adult. This developmental alteration was accompanied by an ipsilesional decrease in propriospinal coordination that is normally established in strict left-right symmetry during metamorphosis in order to synchronize dorsal trunk muscle contractions with bilateral hindlimb extensions in the swimming adult. Our data thus suggest that a disequilibrium in descending vestibulospinal information during Xenopus metamorphosis leads to an altered assembly of adult spinal locomotor circuitry. This in turn enables an adaptive compensation for the dynamic postural asymmetry induced by the vestibular imbalance

  6. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton.

    PubMed

    Gordon, Keith E; Kinnaird, Catherine R; Ferris, Daniel P

    2013-04-01

    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to "fight" the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations. PMID:23307949

  7. Locomotor and verbal distance judgments in action and vista space.

    PubMed

    Bergmann, Johanna; Krauss, Elsa; Münch, Agnes; Jungmann, Reiner; Oberfeld, Daniel; Hecht, Heiko

    2011-04-01

    Judging distances is crucial when interacting with the environment. For short distances in action space (up to 30 m), both explicit verbal estimates and locomotor judgments are fairly accurate. For large distances, data have remained scarce. In two laboratory experiments, our observers judged distances to visual targets presented stereoscopically, either by giving a verbal estimate or by walking the distance to the target on a treadmill. While verbal judgments remained linearly scaled over the whole range of distances from 20 to 262 m, locomotor judgments fell short at distances above 100 m, indicating that observers overestimated the distance they had traveled and increasingly did so as a function of actual target distance. This pattern persisted when controlling for the potential confound of fatigue or reluctance to walk. We discuss different approaches to explain our findings and stress the importance of a differential use of distance cues. A model of leaky path integration showed a good fit with our locomotor data. PMID:21365183

  8. Timing of Locomotor Recovery from Anoxia Modulated by the white Gene in Drosophila.

    PubMed

    Xiao, Chengfeng; Robertson, R Meldrum

    2016-06-01

    Locomotor recovery from anoxia follows the restoration of disordered ion distributions and neuronal excitability. The time taken for locomotor recovery after 30 sec anoxia (around 10 min) is longer than the time for the propagation of action potentials to be restored (<1 min) in Drosophila wild type. We report here that the white (w) gene modulates the timing of locomotor recovery. Wild-type flies displayed fast and consistent recovery of locomotion from anoxia, whereas mutants of w showed significantly delayed and more variable recovery. Genetic analysis including serial backcrossing revealed a strong association between the w locus and the timing of locomotor recovery, and haplo-insufficient function of w(+) in promoting fast recovery. The locomotor recovery phenotype was independent of classic eye pigmentation, although both are associated with the w gene. Introducing up to four copies of mini-white (mw(+)) into w1118 was insufficient to promote fast and consistent locomotor recovery. However, flies carrying w(+) duplicated to the Y chromosome showed wild-type-like fast locomotor recovery. Furthermore, Knockdown of w by RNA interference (RNAi) in neurons but not glia delayed locomotor recovery, and specifically, knockdown of w in subsets of serotonin neurons was sufficient to delay the locomotor recovery. These data reveal an additional role for w in modulating the timing of locomotor recovery from anoxia. PMID:27029736

  9. Adoptive transfer of M2 macrophages promotes locomotor recovery in adult rats after spinal cord injury.

    PubMed

    Ma, Shan-Feng; Chen, Yue-Juan; Zhang, Jing-Xing; Shen, Lin; Wang, Rui; Zhou, Jian-Sheng; Hu, Jian-Guo; Lü, He-Zuo

    2015-03-01

    Classically activated pro-inflammatory (M1) and alternatively activated anti-inflammatory (M2) macrophages populate the local microenvironment after spinal cord injury (SCI). The former type is neurotoxic while the latter has positive effects on neuroregeneration and is less toxic. In addition, while the M1 macrophage response is rapidly induced and sustained, M2 induction is transient. A promising strategy for the repair of SCI is to increase the fraction of M2 cells and prolong their residence time. This study investigated the effect of M2 macrophages induced from bone marrow-derived macrophages on the local microenvironment and their possible role in neuroprotection after SCI. M2 macrophages produced anti-inflammatory cytokines such as interleukin (IL)-10 and transforming growth factor β and infiltrated into the injured spinal cord, stimulated M2 and helper T (Th)2 cells, and produced high levels of IL-10 and -13 at the site of injury. M2 cell transfer decreased spinal cord lesion volume and resulted in increased myelination of axons and preservation of neurons. This was accompanied by significant locomotor improvement as revealed by Basso, Beattie and Bresnahan locomotor rating scale, grid walk and footprint analyses. These results indicate that M2 adoptive transfer has beneficial effects for the injured spinal cord, in which the increased number of M2 macrophages causes a shift in the immunological response from Th1- to Th2-dominated through the production of anti-inflammatory cytokines, which in turn induces the polarization of local microglia and/or macrophages to the M2 subtype, and creates a local microenvironment that is conducive to the rescue of residual myelin and neurons and preservation of neuronal function. PMID:25476600

  10. Daily rhythms in locomotor circuits in Drosophila involve PDF.

    PubMed

    Pírez, Nicolás; Christmann, Bethany L; Griffith, Leslie C

    2013-08-01

    The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep. PMID:23678016

  11. Locomotor-activated neurons of the cat. II. Noradrenergic innervation and colocalization with NEα1a or NEα2b receptors in the thoraco-lumbar spinal cord

    PubMed Central

    Johnson, Dawn M. G.; Riesgo, Mirta I.; Pinzon, Alberto

    2011-01-01

    Norepinephrine (NE) is a strong modulator and/or activator of spinal locomotor networks. Thus noradrenergic fibers likely contact neurons involved in generating locomotion. The aim of the present study was to investigate the noradrenergic innervation of functionally related, locomotor-activated neurons within the thoraco-lumbar spinal cord. This was accomplished by immunohistochemical colocalization of noradrenergic fibers using dopamine-β-hydroxylase or NEα1A and NEα2B receptors with cells expressing the c-fos gene activity-dependent marker Fos. Experiments were performed on paralyzed, precollicular-postmamillary decerebrate cats, in which locomotion was induced by electrical stimulation of the mesencephalic locomotor region. The majority of Fos labeled neurons, especially abundant in laminae VII and VIII throughout the thoraco-lumbar (T13-L7) region of locomotor animals, showed close contacts with multiple noradrenergic boutons. A small percentage (10–40%) of Fos neurons in the T7-L7 segments showed colocalization with NEα1A receptors. In contrast, NEα2B receptor immunoreactivity was observed in 70–90% of Fos cells, with no obvious rostrocaudal gradient. In comparison with results obtained from our previous study on the same animals, a significantly smaller proportion of Fos labeled neurons were innervated by noradrenergic than serotonergic fibers, with significant differences observed for laminae VII and VIII in some segments. In lamina VII of the lumbar segments, the degree of monoaminergic receptor subtype/Fos colocalization examined statistically generally fell into the following order: NEα2B = 5-HT2A ≥ 5-HT7 = 5-HT1A > NEα1A. These results suggest that noradrenergic modulation of locomotion involves NEα1A/NEα2B receptors on noradrenergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments. Further study of the functional role of these receptors in locomotion is warranted. PMID:21307324

  12. High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models.

    PubMed

    Chang, Andrew D; Berges, Victoria A; Chung, Sunho J; Fridman, Gene Y; Baraban, Jay M; Reti, Irving M

    2016-06-01

    Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp2(-/y) and Shank3B(-/-) lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive self-grooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques. PMID:26606849

  13. Spaceflight Sensorimotor Analogs: Simulating Acute and Adaptive Effects

    NASA Technical Reports Server (NTRS)

    Taylor, Laura C.; Harm, Deborah L.; Kozlovskaya, Inessa; Reschke, Millard F.; Wood, Scott J.

    2009-01-01

    Adaptive changes in sensorimotor function during spaceflight are reflected by spatial disorientation, motion sickness, gaze destabilization and decrements in balance, locomotion and eye-hand coordination that occur during and following transitions between different gravitational states. The purpose of this study was to conduct a meta-synthesis of data from spaceflight analogs to evaluate their effectiveness in simulating adaptive changes in sensorimotor function. METHODS. The analogs under review were categorized as either acute analogs used to simulate performance decrements accompanied with transient changes, or adaptive analogs used to drive sensorimotor learning to altered sensory feedback. The effectiveness of each analog was evaluated in terms of mechanisms of action, magnitude and time course of observed deficits compared to spaceflight data, and the effects of amplitude and exposure duration. RESULTS. Parabolic flight has been used extensively to examine effects of acute variation in gravitational loads, ranging from hypergravity to microgravity. More recently, galvanic vestibular stimulation has been used to elicit acute postural, locomotor and gaze dysfunction by disrupting vestibular afferents. Patient populations, e.g., with bilateral vestibular loss or cerebellar dysfunction, have been proposed to model acute sensorimotor dysfunction. Early research sponsored by NASA involved living onboard rotating rooms, which appeared to approximate the time course of adaptation and post-exposure recovery observed in astronauts following spaceflight. Exposure to different bed-rest paradigms (6 deg head down, dry immersion) result in similar motor deficits to that observed following spaceflight. Shorter adaptive analogs have incorporated virtual reality environments, visual distortion paradigms, exposure to conflicting tilt-translation cues, and exposure to 3Gx centrifugation. As with spaceflight, there is considerable variability in responses to most of the analogs

  14. AN IL-1 RECEPTOR ANTAGONIST BLOCKS A MORPHINE-INDUCED ATTENUATION OF LOCOMOTOR RECOVERY AFTER SPINAL CORD INJURY

    PubMed Central

    Hook, Michelle A.; Washburn, Stephanie N.; Moreno, Georgina; Woller, Sarah A.; Puga, Denise; Lee, Kuan H.; Grau, James W.

    2010-01-01

    Morphine is one of the most commonly prescribed medications for the treatment of chronic pain after a spinal cord injury (SCI). Despite widespread use, however, little is known about the secondary consequences of morphine use after SCI. Unfortunately, our previous studies show that administration of a single dose of morphine, in the acute phase of a moderate spinal contusion injury, significantly attenuates locomotor function, reduces weight gain, and produces symptoms of paradoxical pain (Hook et al., 2009). The current study focused on the cellular mechanisms that mediate these effects. Based on data from other models, we hypothesized that pro-inflammatory cytokines might play a role in the morphine-induced attenuation of function. Experiment 1 confirmed that systemic morphine (20 mg/kg) administered one day after a contusion injury significantly increased expression levels of spinal IL-1β 24 hrs later. Experiment 2 extended these findings, demonstrating that a single dose of morphine (90 µg, i.t.) applied directly onto the spinal cord increased expression levels of spinal IL-1β at both 30 min and 24 hrs after administration. Experiment 3 showed that administration of an interleukin-1 receptor antagonist (IL-1ra, i.t.) prior to intrathecal morphine (90 µg), blocked the adverse effects of morphine on locomotor recovery. Further, pre-treatment with 3 µg IL-1ra prevented the increased expression of at-level neuropathic pain symptoms that was observed 28 days later in the group treated with morphine-alone. However, the IL-1ra also had adverse effects that were independent of morphine. Treatment with the IL-1ra alone undermined recovery of locomotor function, potentiated weight loss and significantly increased tissue loss at the injury site. Overall, these data suggest that morphine disrupts a critical balance in concentrations of pro-inflammatory cytokines in the spinal cord, and this undermines recovery of function. PMID:20974246

  15. Cathinone increases body temperature, enhances locomotor activity, and induces striatal c-fos expression in the Siberian hamster.

    PubMed

    Jones, S; Fileccia, E L; Murphy, M; Fowler, M J; King, M V; Shortall, S E; Wigmore, P M; Green, A R; Fone, K C F; Ebling, F J P

    2014-01-24

    Cathinone is a β-keto alkaloid that is the major active constituent of khat, the leaf of the Catha edulis plant that is chewed recreationally in East Africa and the Middle East. Related compounds, such as methcathinone and mephedrone have been increasing in popularity as recreational drugs, resulting in the recent proposal to classify khat as a Class C drug in the UK. There is still limited knowledge of the pharmacological effects of cathinone. This study examined the acute effects of cathinone on core body temperature, locomotor and other behaviors, and neuronal activity in Siberian hamsters. Adult male hamsters, previously implanted with radio telemetry devices, were treated with cathinone (2 or 5mg/kg i.p.), the behavioral profile scored and core body temperature and locomotor activity recorded by radio telemetry. At the end of the study, hamsters received vehicle or cathinone (5mg/kg) and neuronal activation in the brain was determined using immunohistochemical evaluation of c-fos expression. Cathinone dose-dependently induced significant (p<0.0001) increases in both temperature and locomotor activity lasting 60-90min. Cathinone (2mg/kg) increased rearing (p<0.02), and 5mg/kg increased both rearing (p<0.001) and lateral head twitches (p<0.02). Both cathinone doses decreased the time spent at rest (p<0.001). The number of c-fos immunopositive cells were significantly increased in the striatum (p<0.0001) and suprachiasmatic nucleus (p<0.05) following cathinone, indicating increased neuronal activity. There was no effect of cathinone on food intake or body weight. It is concluded that systemic administration of cathinone induces significant behavioral changes and CNS activation in the hamster. PMID:24287379

  16. Age Differences of Salivary Alpha-Amylase Levels of Basal and Acute Responses to Citric Acid Stimulation Between Chinese Children and Adults

    PubMed Central

    Yang, Ze-Min; Chen, Long-Hui; Zhang, Min; Lin, Jing; Zhang, Jie; Chen, Wei-Wen; Yang, Xiao-Rong

    2015-01-01

    It remains unclear how salivary alpha-amylase (sAA) levels respond to mechanical stimuli in different age groups. In addition, the role played by the sAA gene (AMY1) copy number and protein expression (glycosylated and non-glycosylated) in sAA activity has also been rarely reported. In this study, we analyzed saliva samples collected before and after citric acid stimulation from 47 child and 47 adult Chinese subjects. We observed that adults had higher sAA activity and sAA glycosylated levels (glycosylated sAA amount/total sAA amount) in basal and stimulated saliva when compared with children, while no differences were found in total or glycosylated sAA amount between them. Interestingly, adults showed attenuated sAA activity levels increase over those of children after stimulation. Correlation analysis showed that total sAA amount, glycosylated sAA amount, and AMY1 copy number × total sAA amount were all positively correlated with sAA activity before and after stimulation in both groups. Interestingly, correlation r between sAA levels (glycosylated sAA amount and total sAA amount) and sAA activity decreased after stimulation in children, while adults showed an increase in correlation r. In addition, the correlation r between AMY1 copy number × total sAA amount and sAA activity was higher than that between AMY1 copy number, total sAA amount, and sAA activity, respectively. Taken together, our results suggest that total sAA amount, glycosylated sAA amount, and the positive interaction between AMY1 copy number and total sAA amount are crucial in influencing sAA activity before and after stimulation in children and adults. PMID:26635626

  17. Development of a Countermeasure to Mitigate Postflight Locomotor Dysfunction

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Warren, L. E.; Ruttley, T. M.

    2006-01-01

    Astronauts returning from space flight experience locomotor dysfunction following their return to Earth. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially learns to learn and therefore can reorganize more rapidly when faced with a novel adaptive challenge. Evidence for the potential efficacy of an adaptive generalization gait training program can be obtained from numerous studies in the motor learning literature which have demonstrated that systematically varying the conditions of training enhances the ability of the performer to learn and retain a novel motor task. These variable practice training approaches have been used in applied contexts to improve motor skills required in a number of different sports. The central nervous system (CNS) can produce voluntary movement in an almost infinite number of ways. For example, locomotion can be achieved with many different combinations of joint angles, muscle activation patterns and forces. The CNS can exploit these degrees of freedom to enhance motor response adaptability during periods of adaptive flux like that encountered during a change in gravitational environment. Ultimately, the functional goal of an adaptive generalization countermeasure is not necessarily to immediately return movement patterns back to normal. Rather the training regimen should facilitate the reorganization of available sensory and motor subsystems to achieve safe and effective locomotion as soon as possible after long duration space flight. Indeed, this approach has been proposed as a basic feature underlying effective neurological rehabilitation. We have previously confirmed that subjects participating in an adaptive

  18. Locomotor rhythmogenesis in the isolated rat spinal cord: a phase-coupled set of symmetrical flexion–extension oscillators

    PubMed Central

    Juvin, Laurent; Simmers, John; Morin, Didier

    2007-01-01

    The temporal properties of limb motoneuron bursting underlying quadrupedal locomotion were investigated in isolated spinal cord preparations (without or with brainstem attached) taken from 0 to 4-day-old rats. When activated either with differing combinations of N-methyl-d,l-aspartate, serotonin and dopamine, or by electrical stimulation of the brainstem, the spinal cord generated episodes of fictive locomotion with a constant phase relationship between cervical and lumbar ventral root bursts. Alternation occurred between ipsi- and contra-lateral flexor and extensor motor root bursts, and the cervical and lumbar locomotor networks were always active in a diagonal coordination pattern that corresponded to fictive walking. However, unlike typical locomotion in adult animals in which extensor motoneuron bursts vary more with cycle period than flexor bursts, in the isolated neonatal cord, an increase in fictive locomotor speed was associated with a decrease in the durations of both extensor and flexor bursts, at cervical and lumbar levels. To determine whether this symmetry in flexor/extensor phase durations derived from the absence of sensory feedback that is normally provided from the limbs during intact animal locomotion, EMG recordings were made from hindlimb-attached spinal cords during drug-induced locomotor-like movements. Under these conditions, the duration of extensor muscle bursts increased with cycle period, while flexor burst durations now tended to remain constant. Moreover, after a complete dorsal rhizotomy, this extensor dominant pattern was replaced by flexor and extensor muscle bursts of similar duration. In vivo and in vitro experiments were also conducted on older postnatal (P10–12) rats at an age when body-supported adult-like locomotion occurs. Here again, characteristic extensor-dominated burst patterns observed during intact treadmill locomotion were replaced by symmetrical patterns during fictive locomotion expressed by the chemically

  19. Monitoring Locomotor Load in Soccer: Is Metabolic Power, Powerful?

    PubMed

    Buchheit, M; Manouvrier, C; Cassirame, J; Morin, J-B

    2015-12-01

    The aim of the present study was to examine the validity and reliability of metabolic power (P) estimated from locomotor demands during soccer-specific drills. 14 highly-trained soccer players performed a soccer-specific circuit with the ball (3×1-min bouts, interspersed with 30-s passive recovery) on 2 different occasions. Locomotor activity was monitored with 4-Hz GPSs, while oxygen update (VO2) was collected with a portable gas analyzer. P was calculated using either net VO2 responses and traditional calorimetry principles (PVO2, W.kg(-1)) or locomotor demands (PGPS, W.kg(-1)). Distance covered into different speed, acceleration and P zones was recorded. While PGPS was 29±10% lower than PVO2 (d<- 3) during the exercise bouts, it was 85±7% lower (d<- 8) during recovery phases. The typical error between PGPS vs. PVO2 was moderate: 19.8%, 90% confidence limits: (18.4;21.6). The correlation between both estimates of P was small: 0.24 (0.14;0.33). Very large day-to-day variations were observed for acceleration, deceleration and > 20 W.kg(-1) distances (all CVs > 50%), while average Po2 and PGPS showed CVs < 10%. ICC ranged from very low- (acceleration and > 20 W.kg(-1) distances) to-very high (PVO2). PGPS largely underestimates the energy demands of soccer-specific drills, especially during the recovery phases. The poor reliability of PGPS >20 W.kg(-1) questions its value for monitoring purposes in soccer. PMID:26393813

  20. The Drosophila Insulin Receptor Independently Modulates Lifespan and Locomotor Senescence

    PubMed Central

    Boylan, Michael; Achall, Rajesh; Shirras, Alan; Broughton, Susan J.

    2015-01-01

    The Insulin/IGF-like signalling (IIS) pathway plays an evolutionarily conserved role in ageing. In model organisms reduced IIS extends lifespan and ameliorates some forms of functional senescence. However, little is known about IIS in nervous system ageing and behavioural senescence. To investigate this role in Drosophila melanogaster, we measured the effect of reduced IIS on senescence of two locomotor behaviours, negative geotaxis and exploratory walking. Two long-lived fly models with systemic IIS reductions (daGAL4/UAS-InRDN (ubiquitous expression of a dominant negative insulin receptor) and d2GAL/UAS-rpr (ablation of insulin-like peptide producing cells)) showed an amelioration of negative geotaxis senescence similar to that previously reported for the long-lived IIS mutant chico. In contrast, exploratory walking in daGAL4/UAS-InRDN and d2GAL/UAS-rpr flies declined with age similarly to controls. To determine the contribution of IIS in the nervous system to these altered senescence patterns and lifespan, the InRDN was targeted to neurons (elavGAL4/UAS-InRDN), which resulted in extension of lifespan in females, normal negative geotaxis senescence in males and females, and detrimental effects on age-specific exploratory walking behaviour in males and females. These data indicate that the Drosophila insulin receptor independently modulates lifespan and age-specific function of different types of locomotor behaviour. The data suggest that ameliorated negative geotaxis senescence of long-lived flies with systemic IIS reductions is due to ageing related effects of reduced IIS outside the nervous system. The lifespan extension and coincident detrimental or neutral effects on locomotor function with a neuron specific reduction (elavGAL4/UAS-InRDN) indicates that reduced IIS is not beneficial to the neural circuitry underlying the behaviours despite increasing lifespan. PMID:26020640

  1. The Drosophila insulin receptor independently modulates lifespan and locomotor senescence.

    PubMed

    Ismail, Mohd Zamri Bin Haji; Hodges, Matt D; Boylan, Michael; Achall, Rajesh; Shirras, Alan; Broughton, Susan J

    2015-01-01

    The Insulin/IGF-like signalling (IIS) pathway plays an evolutionarily conserved role in ageing. In model organisms reduced IIS extends lifespan and ameliorates some forms of functional senescence. However, little is known about IIS in nervous system ageing and behavioural senescence. To investigate this role in Drosophila melanogaster, we measured the effect of reduced IIS on senescence of two locomotor behaviours, negative geotaxis and exploratory walking. Two long-lived fly models with systemic IIS reductions (daGAL4/UAS-InRDN (ubiquitous expression of a dominant negative insulin receptor) and d2GAL/UAS-rpr (ablation of insulin-like peptide producing cells)) showed an amelioration of negative geotaxis senescence similar to that previously reported for the long-lived IIS mutant chico. In contrast, exploratory walking in daGAL4/UAS-InRDN and d2GAL/UAS-rpr flies declined with age similarly to controls. To determine the contribution of IIS in the nervous system to these altered senescence patterns and lifespan, the InRDN was targeted to neurons (elavGAL4/UAS-InRDN), which resulted in extension of lifespan in females, normal negative geotaxis senescence in males and females, and detrimental effects on age-specific exploratory walking behaviour in males and females. These data indicate that the Drosophila insulin receptor independently modulates lifespan and age-specific function of different types of locomotor behaviour. The data suggest that ameliorated negative geotaxis senescence of long-lived flies with systemic IIS reductions is due to ageing related effects of reduced IIS outside the nervous system. The lifespan extension and coincident detrimental or neutral effects on locomotor function with a neuron specific reduction (elavGAL4/UAS-InRDN) indicates that reduced IIS is not beneficial to the neural circuitry underlying the behaviours despite increasing lifespan. PMID:26020640

  2. Locomotor energetics and leg length in hominid bipedality.

    PubMed

    Kramer, P A; Eck, G G

    2000-05-01

    Because bipedality is the quintessential characteristic of Hominidae, researchers have compared ancient forms of bipedality with modern human gait since the first clear evidence of bipedal australopithecines was unearthed over 70 years ago. Several researchers have suggested that the australopithecine form of bipedality was transitional between the quadrupedality of the African apes and modern human bipedality and, consequently, inefficient. Other researchers have maintained that australopithecine bipedality was identical to that of Homo. But is it reasonable to require that all forms of hominid bipedality must be the same in order to be optimized? Most attempts to evaluate the locomotor effectiveness of the australopithecines have, unfortunately, assumed that the locomotor anatomy of modern humans is the exemplar of consummate bipedality. Modern human anatomy is, however, the product of selective pressures present in the particular milieu in which Homo arose and it is not necessarily the only, or even the most efficient, bipedal solution possible. In this report, we investigate the locomotion of Australopithecus afarensis, as represented by AL 288-1, using standard mechanical analyses. The osteological anatomy of AL 288-1 and movement profiles derived from modern humans are applied to a dynamic model of a biped, which predicts the mechanical power required by AL 288-1 to walk at various velocities. This same procedure is used with the anatomy of a composite modern woman and a comparison made. We find that AL 288-1 expends less energy than the composite woman when locomoting at walking speeds. This energetic advantage comes, however, at a price: the preferred transition speed (from a walk to a run) of AL 288-1 was lower than that of the composite woman. Consequently, the maximum daily range of AL 288-1 may well have been substantially smaller than that of modern people. The locomotor anatomy of A. afarensis may have been optimized for a particular ecological niche

  3. Genetic NMDA receptor deficiency disrupts acute and chronic effects of cocaine but not amphetamine.

    PubMed

    Ramsey, Amy J; Laakso, Aki; Cyr, Michel; Sotnikova, Tatyana D; Salahpour, Ali; Medvedev, Ivan O; Dykstra, Linda A; Gainetdinov, Raul R; Caron, Marc G

    2008-10-01

    NMDA receptor-mediated glutamate transmission is required for several forms of neuronal plasticity. Its role in the neuronal responses to addictive drugs is an ongoing subject of investigation. We report here that the acute locomotor-stimulating effect of cocaine is absent in NMDA receptor-deficient mice (NR1-KD). In contrast, their acute responses to amphetamine and to direct dopamine receptor agonists are not significantly altered. The striking attenuation of cocaine's acute effects is not likely explained by alterations in the dopaminergic system of NR1-KD mice, since most parameters of pre- and postsynaptic dopamine function are unchanged. Consistent with the behavioral findings, cocaine induces less c-Fos expression in the striatum of these mice, while amphetamine-induced c-Fos expression is intact. Furthermore, chronic cocaine-induced sensitization and conditioned place preference are attenuated and develop more slowly in mutant animals, but amphetamine's effects are not altered significantly. Our results highlight the importance of NMDA receptor-mediated glutamatergic transmission specifically in cocaine actions, and support a hypothesis that cocaine and amphetamine elicit their effects through differential actions on signaling pathways. PMID:18185498

  4. Locomotor Dysfunction after Spaceflight: Characterization and Countermeasure Development

    NASA Technical Reports Server (NTRS)

    Mulavara, A. P.; Cohen, H. S.; Peters, B. T.; Miller, C. A.; Brady, R.; Bloomberg, Jacob J.

    2007-01-01

    Astronauts returning from space flight show disturbances in locomotor control manifested by changes in various sub-systems including head-trunk coordination, dynamic visual acuity, lower limb muscle activation patterning and kinematics (Glasauer, et al., 1995; Bloomberg, et al., 1997; McDonald, et al., 1996; 1997; Layne, et al., 1997; 1998, 2001, 2004; Newman, et al., 1997; Bloomberg and Mulavara, 2003). These post flight changes in locomotor performance, due to neural adaptation to the microgravity conditions of space flight, affect the ability of crewmembers especially after a long duration mission to egress their vehicle and perform extravehicular activities soon after landing on Earth or following a landing on the surface of the Moon or Mars. At present, no operational training intervention is available pre- or in- flight to mitigate post flight locomotor disturbances. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially "learns to learn" and therefore can reorganize more rapidly when faced with a novel adaptive challenge. Ultimately, the functional goal of an adaptive generalization countermeasure is not necessarily to immediately return movement patterns back to "normal". Rather the training regimen should facilitate the reorganization of available sensorimotor sub-systems to achieve safe and effective locomotion as soon as possible after space flight. We have previously confirmed that subjects participating in adaptive generalization training programs, using a variety of visuomotor distortions and different motor tasks from throwing to negotiating an obstacle course as the dependent measure, can learn to enhance their ability to adapt to a

  5. Predictive Measures of Locomotor Performance on an Unstable Walking Surface

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Caldwell, E. E.; Batson, C. D.; De Dios, Y. E.; Gadd, N. E.; Goel, R.; Wood, S. J.; Cohen, H. S.; Oddsson, L. I.; Seidler, R. D.

    2016-01-01

    Locomotion requires integration of visual, vestibular, and somatosensory information to produce the appropriate motor output to control movement. The degree to which these sensory inputs are weighted and reorganized in discordant sensory environments varies by individual and may be predictive of the ability to adapt to novel environments. The goals of this project are to: 1) develop a set of predictive measures capable of identifying individual differences in sensorimotor adaptability, and 2) use this information to inform the design of training countermeasures designed to enhance the ability of astronauts to adapt to gravitational transitions improving balance and locomotor performance after a Mars landing and enhancing egress capability after a landing on Earth.

  6. Evidence for a daily rhythmicity in the acute release of luteinizing hormone in response to electrical stimulation in the Japanese quail.

    PubMed

    Konishi, H; Foster, R G; Follett, B K

    1987-08-01

    This study was undertaken to examine the effect of electrical stimulation of the hypothalamus at different times of day on luteinizing hormone (LH) secretion in male castrated quail on short days (8L:16D). The posterior hypothalamus was stimulated with square-wave pulses of 80 microA for 2 min through chronically-implanted platinum microelectrodes. Stimulation was carried out on each quail at 4 (treatment A), 10 (B), or 14 h (C) after dawn. Plasma LH levels were increased markedly within 2 min of ending the stimulation but reached basal levels again over the next 20 min or so. The absolute increase was significantly greater in treatment B (10 h after lights on) than at the other times tested. This is consistent with a rhythm in hypothalamic responsivity. The results are discussed in the context of the rhythm of photoinducibility which occurs early in the night and which is used by quail as a photoperiodic clock to regulate seasonal reproduction. PMID:3625579

  7. Locomotor activity changes on zebrafish larvae with different 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) embryonic exposure modes.

    PubMed

    Zhao, Jing; Xu, Ting; Yin, Da-Qiang

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants and are banned around the world as potent environmental contaminants. PBDE-47 is the most concerned PBDE with its environmental prevalence and various toxicity characteristics including neurotoxicity. In this paper, we studied larval zebrafish behavioral alterations caused by PBDE-47 neurotoxicity. The light-dark cycle stimulation was used to investigate the locomotor changes of zebrafish larvae at different ages (4-6 day post-fertilization, dpf) after PBDE-47 exposure (5, 50, 500 μg L(-1)). Three exposure modes, namely continuous exposure, early pulse exposure and interval exposure, were adopted to assess and compare the impacts of exposure modes on larval zebrafish locomotion. Our results showed that locomotor effects upon PBDE exposure depended on the specific exposure mode studied. In the early pulse exposure mode, the locomotion of zebrafish larvae did not change significantly at all PBDE-47 concentrations tested. In contrast, for both the continuous exposure and interval exposure modes, the highest dose of PBDE-47 (500 μg L(-1)) elicited pronounced hypoactivity at 5 dpf during dark periods except for the initial one. However, at 6 dpf, hypoactivity was only observed in the continuously exposed zebrafish larvae (to an even higher degree compared to 5 dpf), but not in the interval exposure treatment group. Our results suggested that the conventional, continuous exposure mode might not be enough to evaluate the toxicity of chemicals in the real environments. PMID:24080000

  8. Toxicity of organophosphates on morphology and locomotor behavior in brine shrimp, Artemia salina.

    PubMed

    Venkateswara Rao, J; Kavitha, P; Jakka, N M; Sridhar, V; Usman, P K

    2007-08-01

    The acute toxicity and hatching success of four organophosphorus insecticides--acephate (ACEP), chlorpyrifos (CPP), monocrotophos (MCP), and profenofos (PF)--was studied in a short-term bioassay using brine shrimp, Artemia salina. Fifty percent hatchability inhibition concentration and median lethal concentration (LC(50)) values were calculated after probit transformation of the resulting data. Among the insecticides tested, CPP is found to be the most toxic and also to inhibit hatching success of A. salina cysts in a concentration-dependent manner. In addition, the effect of these pesticides on locomotor behavior (swimming speed) and morphologic differences were studied in LC(50)-exposed nauplii after 24 hours. The in vivo effect of these insecticides on acetylcholinesterase (Enzyme commission number (EC 3.1.1.7) activity was also determined in LC(50)-exposed nauplii after 24 hours. Maximum percent decrease in their swimming speed and significant morphologic alterations were noticed in CPP-exposed brine shrimps. The order of toxicity was CPP > PF > MCP > ACEP in all the parameters studied. PMID:17549541

  9. Locomotor behavior and long bone morphology in individual free-ranging chimpanzees.

    PubMed

    Carlson, Kristian J; Doran-Sheehy, Diane M; Hunt, Kevin D; Nishida, Toshisada; Yamanaka, Atsushi; Boesch, Christophe

    2006-04-01

    We combine structural limb data and behavioral data for free-ranging chimpanzees from Taï (Ivory Coast) and Mahale National Parks (Tanzania) to begin to consider the relationship between individual variation in locomotor activity and morphology. Femoral and humeral cross sections of ten individuals were acquired via computed tomography. Locomotor profiles of seven individuals were constructed from 3387 instantaneous time-point observations (87.4 hours). Within the limited number of suitable chimpanzees, individual variation in locomotor profiles displayed neither clear nor consistent trends with diaphyseal cross-sectional shapes. The percentages of specific locomotor modes did not relate well to diaphyseal shapes since neither infrequent nor frequent locomotor modes varied consistently with shapes. The percentage of arboreal locomotion, rather than estimated body mass, apparently had comparatively greater biological relevance to variation in diaphyseal shape. The mechanical consequences of locomotor modes on femoral and humeral diaphyseal shapes (e.g., orientation of bending strains) may overlap between naturalistic modes more than currently is recognized. Alternatively, diaphyseal shape may be unresponsive to mechanical demands of these specific locomotor modes. More data are needed in order to discern between these possibilities. Increasing the sample to include additional free-ranging chimpanzees, or primates in general, as well as devoting more attention to the mechanics of a greater variety of naturalistic locomotor modes would be fruitful to understanding the behavioral basis of diaphyseal shapes. PMID:16376413

  10. Locomotor Tests Predict Community Mobility in Children and Youth with Cerebral Palsy

    ERIC Educational Resources Information Center

    Ferland, Chantale; Moffet, Helene; Maltais, Desiree

    2012-01-01

    Ambulatory children and youth with cerebral palsy have limitations in locomotor capacities and in community mobility. The ability of three locomotor tests to predict community mobility in this population (N = 49, 27 boys, 6-16 years old) was examined. The tests were a level ground walking test, the 6-min-Walk-Test (6MWT), and two tests of advanced…

  11. Differences in the neurochemical and behavioural profiles of lisdexamfetamine methylphenidate and modafinil revealed by simultaneous dual-probe microdialysis and locomotor activity measurements in freely-moving rats.

    PubMed

    Rowley, Helen L; Kulkarni, Rajiv S; Gosden, Jane; Brammer, Richard J; Hackett, David; Heal, David J

    2014-03-01

    Lisdexamfetamine dimesylate is a novel prodrug approved in North America, Europe and Brazil for treating attention deficit hyperactivity disorder (ADHD). It undergoes rate-limited hydrolysis by red blood cells to yield d-amphetamine. Following our previous work comparing lisdexamfetamine with d-amphetamine, the neurochemical and behavioural profiles of lisdexamfetamine, methylphenidate and modafinil were compared by dual-probe microdialysis in the prefrontal cortex (PFC) and striatum of conscious rats with simultaneous locomotor activity measurement. We employed pharmacologically equivalent doses of all compounds and those that spanned the therapeutically relevant and psychostimulant range. Lisdexamfetamine (0.5, 1.5, 4.5 mg/kg d-amphetamine base, per os (po)), methylphenidate (3, 10, 30 mg/kg base, po) and modafinil (100, 300, 600 mg/kg base, po) increased efflux of dopamine and noradrenaline in PFC, and dopamine in striatum. Only lisdexamfetamine increased 5-hydroxytryptamine (5-HT) efflux in PFC and striatum. Lisdexamfetamine had larger and more sustained effects on catecholaminergic neurotransmission than methylphenidate or modafinil. Linear correlations were observed between striatal dopamine efflux and locomotor activity for lisdexamfetamine and methylphenidate, but not modafinil. Regression slopes revealed greater increases in extracellular dopamine could be elicited without producing locomotor activation by lisdexamfetamine than methylphenidate. These results are consistent with clinical findings showing that lisdexamfetamine is an effective ADHD medication with prolonged duration of action and good separation between its therapeutic actions and stimulant side-effects. PMID:24327450

  12. Locomotor Trajectories of Stroke Patients during Oriented Gait and Turning

    PubMed Central

    Van Hamme, Angele; Bensmail, Djamel

    2016-01-01

    Background The Timed Up and Go (TUG) test is widely used to assess locomotion in patients with stroke and is considered to predict the risk of falls. The analysis of locomotor trajectories during the TUG appears pertinent in stroke patients. The aims of this study were i) to analyze locomotor trajectories in patients with stroke during the walking and turning sub-tasks of the TUG, and to compare them with healthy subjects, ii) to determine whether trajectory parameters provide additional information to that provided by the conventional measure (performance time), iii) to compare the trajectory parameters of fallers and non-fallers with stroke and of patients with right and left hemisphere stroke, and iv) to evaluate correlations between trajectory parameters and Berg Balance Scale scores. Methods 29 patients with stroke (mean age 54.2±12.2 years, 18 men, 8 fallers) and 25 healthy subjects (mean age 51.6±8.7 years, 11 men) underwent three-dimensional analysis of the TUG. The trajectory of the center of mass was analyzed by calculation of the global trajectory length, Hausdorff distance and Dynamic Time Warping. The parameters were compared with a reference trajectory during the total task and each sub-task (Go, Turn, Return) of the TUG. Results Values of trajectory parameters were significantly higher for the stroke group during the total TUG and the Go and Turn sub-tasks (p<0.05). Moreover, logistic regression indicated that these parameters better discriminated stroke patients and healthy subjects than the conventional timed performance during the Go sub-task. In addition, fallers were distinguished by higher Dynamic Time Warping during the Go (p<0.05). There were no differences between patients with right and left hemisphere stroke. Discussion and Conclusion The trajectories of the stroke patients were longer and more deviated during the turn and the preceding phase. Trajectory parameters provided additional information to timed performance of this locomotor

  13. Mechanisms of Acute Eosinophil Mobilization from the Bone Marrow Stimulated by Interleukin 5: The Role of Specific Adhesion Molecules and Phosphatidylinositol 3-Kinase

    PubMed Central

    Palframan, Roger T.; Collins, Paul D.; Severs, Nicholas J.; Rothery, Stephen; Williams, Timothy J.; Rankin, Sara M.

    1998-01-01

    Mobilization of bone marrow eosinophils is a critical early step in their trafficking to the lung during allergic inflammatory reactions. We have shown previously that the cytokine interleukin (IL)-5, generated during an allergic inflammatory reaction in the guinea pig, acts systemically to mobilize eosinophils from the bone marrow. Here, we have investigated the mechanisms underlying this release process. Examination by light and electron microscopy revealed the rapid migration of eosinophils from the hematopoietic compartment and across the bone marrow sinus endothelium in response to IL-5. Using an in situ perfusion system of the guinea pig hind limb, we showed that IL-5 stimulated a dose-dependent selective release of eosinophils from the bone marrow. Eosinophils released from the bone marrow in response to IL-5 expressed increased levels of β2 integrin and a decrease in L-selectin, but no change in α4 integrin levels. A β2 integrin–blocking antibody markedly inhibited the mobilization of eosinophils from the bone marrow stimulated by IL-5. In contrast, an α4 integrin blocking antibody increased the rate of eosinophil mobilization induced by IL-5. In vitro we demonstrated that IL-5 stimulates the selective chemokinesis of bone marrow eosinophils, a process markedly inhibited by two structurally distinct inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002. Wortmannin was also shown to block eosinophil release induced by IL-5 in the perfused bone marrow system. The parallel observations on the bone marrow eosinophil release process and responses in isolated eosinophils in vitro suggest that eosinophil chemokinesis is the driving force for release in vivo and that this release process is regulated by α4 and β2 integrins acting in opposite directions. PMID:9802974

  14. Insulin-induced hypoglycaemia is co-ordinately regulated by liver and muscle during acute and chronic insulin stimulation in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Polakof, Sergio; Skiba-Cassy, Sandrine; Choubert, Georges; Panserat, Stéphane

    2010-05-01

    The relative glucose intolerance of carnivorous fish species is often proposed to be a result of poor peripheral insulin action or possibly insulin resistance. In the present study, data from aortic cannulated rainbow trout receiving bovine insulin (75 mIU kg(-1)) injections show for the first time their ability to clear glucose in a very efficient manner. In another set of experiments, mRNA transcripts and protein phosphorylation status of proteins controlling glycaemia and glucose-related metabolism were studied during both acute and chronic treatment with bovine insulin. Our results show that fasted rainbow trout are well adapted at the molecular level to respond to increases in circulating insulin levels, and that this hormone is able to potentially improve glucose distribution and uptake by peripheral tissues. After acute insulin administration we found that to counter-regulate the insulin-induced hypoglycaemia, trout metabolism is strongly modified. This short-term, efficient response to hypoglycaemia includes a rapid, coordinated response involving the reorganization of muscle and liver metabolism. During chronic insulin treatment some of the functions traditionally attributed to insulin actions in mammals were observed, including increased mRNA levels of glucose transporters and glycogen storage (primarily in the muscle) as well as decreased mRNA levels of enzymes involved in de novo glucose production (in the liver). Finally, we show that the rainbow trout demonstrates most of the classic metabolic adjustments employed by mammals to efficiently utilize glucose in the appropriate insulin context. PMID:20400628

  15. Individual Differences in Ethanol Locomotor Sensitization Are Associated with Dopamine D1 Receptor Intra-Cellular Signaling of DARPP-32 in the Nucleus Accumbens

    PubMed Central

    Abrahao, Karina Possa; Oliveira Goeldner, Francine; Souza-Formigoni, Maria Lucia Oliveira

    2014-01-01

    In mice there are clear individual differences in the development of behavioral sensitization to ethanol, a progressive potentiation of its psychomotor stimulant effect. Variability in the behavioral responses to ethanol has been associated with alcohol preference. Here we investigated if the functional hyperresponsiveness of D1 receptors observed in ethanol sensitized mice leads to an increased activation of DARPP-32, a central regulatory protein in medium spiny neurons, in the nucleus accumbens - a brain region known to play a role in drug reinforcement. Swiss Webster mice received ethanol (2.2 g/kg/day) or saline i.p. administrations for 21 days and were weekly evaluated regarding their locomotor activity. From those treated with ethanol, the 33% with the highest levels of locomotor activity were classified as “sensitized” and the 33% with the lowest levels as "non-sensitized”. The latter presented similar locomotor levels to those of saline-treated mice. Different subgroups of mice received intra-accumbens administrations of saline and, 48 h later, SKF-38393, D1 receptor agonist 0.1 or 1 µg/side. Indeed, sensitized mice presented functional hyperresponsiveness of D1 receptors in the accumbens. Two weeks following the ethanol treatment, other subgroups received systemic saline or SKF 10 mg/kg, 20 min before the euthanasia. The nucleus accumbens were dissected for the Western Blot analyses of total DARPP-32 and phospho-Thr34-DARPP-32 expression. D1 receptor activation induced higher phospho-Thr34-DARPP-32 expression in sensitized mice than in non-sensitized or saline. The functionally hyperresponsiveness of D1 receptors in the nucleus accumbens is associated with an increased phospho-Thr34-DARPP-32 expression after D1 receptor activation. These data suggest that an enduring increase in the sensitivity of the dopamine D1 receptor intracellular pathway sensitivity represents a neurobiological correlate associated with the development of locomotor

  16. The effects of radio-frequency lesions of the nucleus accumbens on d-amphetamine-induced locomotor and rearing behavior in rats.

    PubMed

    Kehne, J H; Sant, W W; Sorenson, C A

    1981-01-01

    A large body of evidence supports the conclusion that mesolimbic dopaminergic neurons, particularly those that innervate the nucleus accumbens (n. ACC), are important for the expression of amphetamine-stimulated locomotor behavior (ASLB). However, a contradictory report (Wirtshafter et al. 1978), stating that bilateral lesions of the n. ACC fail to block ASLB, was based on a general measure of activity that did not distinguish between locomotion and rearing. In the present study, observer ratings of videotaped responses were used to determine the separate effects of 2.0 mg/kg d-amphetamine (d-AMP) on locomotion and rearing in rats with either sham or radio-frequency lesions of the n. ACC. The n.ACC lesions blocked the locomotor stimulation, but not the increased rearing that follows d-AMP administration. These results support the general conclusion that dopaminergic terminals in the n. ACC are important for the expression of ASLB, and further suggest that d-AMP-stimulated locomotion and rearing are mediated through different neural substrates. PMID:6803281

  17. Microcomputerized measurement of the circadian locomotor rhythm in microorganisms.

    PubMed

    Tanakadate, A; Ishikawa, H; Hasegawa, K

    1985-02-01

    A computerized close-up video/photoamplifier system was implemented for the study of circadian locomotor rhythm in a population of a ciliate protozoan, Paramecium. This fully microcomputerized system facilitated automatic long-term measurement of three parameters in parallel: (1) numbers of specimens per 10 min traversing beneath a fixed point in an experimental vessel, (2) times taken by specimens to traverse the point, and (3) interval times between subsequent specimens traversing the point. Stochastic analyses using these parameters can derive the circadian fluctuation of physiological variables, such as swimming speed and the frequency of avoiding reaction (abrupt change in swimming direction). The computerized system simultaneously accomplished the acquisition of these three sets of data, their transient storage, and their graphic display according to given format. The system software was constituted so that an experimenter with little computer knowledge, could easily operate the system by answering questions displayed on the computer monitor. PMID:3839082

  18. EEG during pedaling: Evidence for cortical control of locomotor tasks

    PubMed Central

    Jain, Sanket; Gourab, Krishnaj; Schindler-Ivens, Sheila; Schmit, Brian D.

    2014-01-01

    Objective This study characterized the brain electrical activity during pedaling, a locomotor-like task, in humans. We postulated that phasic brain activity would be associated with active pedaling, consistent with a cortical role in locomotor tasks. Methods Sixty four channels of electroencephalogram (EEG) and 10 channels of electromyogram (EMG) data were recorded from 10 neurologically-intact volunteers while they performed active and passive (no effort) pedaling on a custom-designed stationary bicycle. Ensemble averaged waveforms, 2 dimensional topographic maps and amplitude of the β (13–35 Hz) frequency band were analyzed and compared between active and passive trials. Results The peak-to-peak amplitude (peak positive–peak negative) of the EEG waveform recorded at the Cz electrode was higher in the passive than the active trials (p < 0.01). β-band oscillations in electrodes overlying the leg representation area of the cortex were significantly desynchronized during active compared to the passive pedaling (p < 0.01). A significant negative correlation was observed between the average EEG waveform for active trials and the composite EMG (summated EMG from both limbs for each muscle) of the rectus femoris (r = −0.77, p < 0.01) the medial hamstrings (r = −0.85, p < 0.01) and the tibialis anterior (r = −0.70, p < 0.01) muscles. Conclusions These results demonstrated that substantial sensorimotor processing occurs in the brain during pedaling in humans. Further, cortical activity seemed to be greatest during recruitment of the muscles critical for transitioning the legs from flexion to extension and vice versa. Significance This is the first study demonstrating the feasibility of EEG recording during pedaling, and owing to similarities between pedaling and bipedal walking, may provide valuable insight into brain activity during locomotion in humans. PMID:23036179

  19. Novel locomotor muscle design in extreme deep-diving whales.

    PubMed

    Velten, B P; Dillaman, R M; Kinsey, S T; McLellan, W A; Pabst, D A

    2013-05-15

    Most marine mammals are hypothesized to routinely dive within their aerobic dive limit (ADL). Mammals that regularly perform deep, long-duration dives have locomotor muscles with elevated myoglobin concentrations that are composed of predominantly large, slow-twitch (Type I) fibers with low mitochondrial volume densities (V(mt)). These features contribute to extending ADL by increasing oxygen stores and decreasing metabolic rate. Recent tagging studies, however, have challenged the view that two groups of extreme deep-diving cetaceans dive within their ADLs. Beaked whales (including Ziphius cavirostris and Mesoplodon densirostris) routinely perform the deepest and longest average dives of any air-breathing vertebrate, and short-finned pilot whales (Globicephala macrorhynchus) perform high-speed sprints at depth. We investigated the locomotor muscle morphology and estimated total body oxygen stores of several species within these two groups of cetaceans to determine whether they (1) shared muscle design features with other deep divers and (2) performed dives within their calculated ADLs. Muscle of both cetaceans displayed high myoglobin concentrations and large fibers, as predicted, but novel fiber profiles for diving mammals. Beaked whales possessed a sprinter's fiber-type profile, composed of ~80% fast-twitch (Type II) fibers with low V(mt). Approximately one-third of the muscle fibers of short-finned pilot whales were slow-twitch, oxidative, glycolytic fibers, a rare fiber type for any mammal. The muscle morphology of beaked whales likely decreases the energetic cost of diving, while that of short-finned pilot whales supports high activity events. Calculated ADLs indicate that, at low metabolic rates, both beaked and short-finned pilot whales carry sufficient onboard oxygen to aerobically support their dives. PMID:23393275

  20. Involvement of Glutamate NMDA Receptors in the Acute, Long-Term, and Conditioned Effects of Amphetamine on Rat 50kHz Ultrasonic Vocalizations

    PubMed Central

    Costa, Giulia; Morelli, Micaela

    2015-01-01

    Background: Rats emit 50kHz ultrasonic vocalizations (USVs) in response to either natural or pharmacological pleasurable stimuli, and these USVs have emerged as a new behavioral measure for investigating the motivational properties of drugs. Earlier studies have indicated that activation of the dopaminergic system is critically involved in 50kHz USV emissions. However, evidence also exists that non-dopaminergic neurotransmitters participate in this behavioral response. Methods: To ascertain whether glutamate transmission plays a role in 50kHz USV emissions stimulated by amphetamine, rats received five amphetamine (1–2mg/kg, i.p.) administrations on alternate days in a test cage, either alone or combined with the glutamate N-methyl-D-aspartate receptor antagonist MK-801 (0.1–0.5mg/kg, i.p.). Seven days after treatment discontinuation, rats were re-exposed to the test cage to assess drug conditioning, and afterwards received a drug challenge. USVs and locomotor activity were evaluated, along with immunofluorescence for Zif-268 in various brain regions and spontaneous alternation in a Y maze. Results: Amphetamine-treated rats displayed higher 50kHz USV emissions and locomotor activity than vehicle-treated rats, and emitted conditioned vocalizations on test cage re-exposure. Rats co-administered amphetamine and MK-801 displayed lower and dose-dependent 50kHz USV emissions, but not lower locomotor activity, during repeated treatment and challenge, and scarce conditioned vocalization compared with amphetamine-treated rats. These effects were associated with lower levels of Zif-268 after amphetamine challenge and spontaneous alternation deficits. Conclusions: These results indicate that glutamate transmission participates in the acute, long-term, and conditioned effects of amphetamine on 50kHz USVs, possibly by influencing amphetamine-induced long-term neuronal changes and/or amphetamine-associated memories. PMID:25991653

  1. Acute Toxicity and General Pharmacological Action of QGC EXT

    PubMed Central

    Lee, Jong Mi; Im, Wi Joon; Nam, Yoon Jin; Oh, Kyung Hoon; Lim, Jae Chun; Whang, Wan Kyunn

    2012-01-01

    It has been shown that QGC isolated and purified from Rumecis folium found protective effects of gastritis and esophagitis which EXT is an ethanol extract of it. We examined acute toxicity and the general pharmacological action of QGC EXT to search for any side effects of it in rats, mice, guinea pigs, and cats. In a single dose toxicity study, QGC EXT didn't show toxicological effects in rats and mice, and the LD50 was over 5 g/kg in both animals, and there were also no changes in weight, feed and water intake during these toxicological experimental periods. We examined the general pharmacological action on central controlled behavior responses, and peripheral organs including blood pressure, heart rate, respiration and gastrointestinal system, We found that there were no significant changes in body temperature, locomotors activity, stereotyped behaviors, sleeping time, and convulsion. In other studies, writhing reaction, normal body temperature, there did not appear to be any changes. The large intestine movement and electrical field stimulation-induced contraction was not changes by its EXT. In addition, the influences on blood pressure, heart rates, and respiration by QGC EXT were not found. These results indicate that QGC EXT may be very safe as a new drug, since its LD50 was very high over 5 g/kg and any side effects were not found. PMID:22416220

  2. Deep brain stimulation affects conditioned and unconditioned anxiety in different brain areas.

    PubMed

    van Dijk, A; Klanker, M; van Oorschot, N; Post, R; Hamelink, R; Feenstra, M G P; Denys, D

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive-compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC. PMID:23900312

  3. Effect of stimulating the lumbar skin caudal to a complete spinal cord injury on hindlimb locomotion.

    PubMed

    Hurteau, Marie-France; Thibaudier, Yann; Dambreville, Charline; Desaulniers, Corinne; Frigon, Alain

    2015-01-15

    Sensory feedback is a potent modulator of the locomotor pattern generated by spinal networks. The purpose of this study was to assess the effect of cutaneous inputs from the back on the spinal-generated locomotor pattern. The spinal cord of six adult cats was transected at low thoracic levels. Cats were then trained to recover hindlimb locomotion. During experiments, the skin overlying lumbar vertebrae L2 to L7 was mechanically stimulated by a small calibrated clip or by manual pinching. Trials without and with cutaneous stimulation were performed at a treadmill speed of 0.4 m/s. Although manually pinching the skin completely stopped hindlimb locomotion and abolished weight support, cutaneous stimulation with the calibrated clip produced smaller effects. Specifically, more focalized cutaneous stimulation with the clip reduced flexor and extensor muscle activity and led to a more caudal positioning of the paw at contact and liftoff. Moreover, cutaneous stimulation with the clip led to a greater number of steps with improper nonplantigrade paw placements at contact and paw drag at the stance-to-swing transition. The most consistent effects on the hindlimb locomotor pattern were observed with cutaneous stimulation at midlumbar levels, from L3 to L5. The results indicate that cutaneous stimulation of the skin modulates the excitability of spinal circuits involved in generating locomotion and weight support, particularly at spinal segments thought to be critical for rhythm generation. PMID:25339715

  4. Effects of Deep Electroacupuncture Stimulation at “Huantiao” (GB 30) on Expression of Apoptosis-Related Factors in Rats with Acute Sciatic Nerve Injury

    PubMed Central

    Dai, Lili; Han, Yanjing; Ma, Tieming; Liu, Yuli; Ren, Lu; Bai, Zenghua; Li, Ye

    2015-01-01

    SD rats were randomly divided into normal control, model, deep EA, and shallow EA groups. The model was established by mechanical clamping of the sciatic nerve stem. For deep and shallow EA, the needles were inserted into “Huantiao” (GB 30) by about 16 mm and 7 mm, respectively, once daily for 14 days. The results showed that, compared with the normal control group, the nerve-muscle excitability of rat's hip muscle decreased and the nerve conduction velocity of sciatic nerve slowed down in the model group; meanwhile, the number of apoptotic cells and the expression level of Bax protein in the injured nerve increased significantly, and the expression level of Bcl-2 protein and the ratio of Bcl-2/Bax decreased considerably. Compared with the model group, the indices mentioned above were reversed in the two treatment groups, and the changes in the deep EA group were more significant than those in the shallow EA group. These results indicate that EA stimulation at GB 30 can improve the function of injured sciatic nerve, which is closely associated with its effects in upregulating the expression of apoptosis inhibitive factor Bcl-2 and downregulating apoptosis promotive factor Bax. Deep EA is relatively better. PMID:26167187

  5. Stereoselective Effects of Abused “Bath Salt” Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation

    PubMed Central

    Gannon, Brenda M.; Williamson, Adrian; Suzuki, Masaki; Rice, Kenner C.

    2016-01-01

    3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit “bath salts” products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(−)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(−)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(−)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(−)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(−)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse. PMID:26769917

  6. Enhancement of amphetamine-induced locomotor response in rats on different regimens of diet restriction and 2-deoxy-D-glucose treatment.

    PubMed

    Mamczarz, J; Bowker, J L; Duffy, K; Zhu, M; Hagepanos, A; Ingram, D K

    2005-01-01

    Diet restriction (DR) in rodents increases lifespan, reduces age-related disease and pathology, increases stress responses, and maintains better function later into life compared with conventional ad libitum (AL) feeding. We have been investigating different DR regimens and also DR mimetics that stimulate stress response pathways that are activated by DR. By inhibiting glycolysis, feeding or injection of 2-deoxy-D-glucose (2DG) has been proposed as a DR mimetic and has been shown to provide neuroprotection. In the current study, we examined whether 2DG treatment produces behavioral changes similar to those observed in DR rats following stimulation of the dopaminergic (DA) system by D-amphetamine (AMPH). Male Fischer 344 rats were maintained on different dietary regimens: 40% daily DR (40% DR); every-other-day feeding (EOD); or AL with some groups provided food containing 0.4% 2DG or injected i.p. with 2DG. In addition, we examined the persistence of effects of DR or 2DG feeding after switching rats to AL. When locomotor activity was assessed at different time points following initiation of dietary treatments, we noted that the enhancement of AMPH-induced locomotor responses emerged earlier in DR rats than observed in 2DG fed rats, but 40% DR and EOD rats responded in a similar manner. Enhanced locomotor responses persisted in 2DG fed rats even when returned to normal diet for 1 month and in the case of DR rats even after 2 months of AL feeding. Three weeks of 2DG injections also enhanced AMPH response, but this effect was transient. The most important finding was that 2DG did not affect body weight or diet intake yet had effects similar to DR. Thus, 2DG appears to activate DA pathways in the same direction as DR does but without the necessity of reducing caloric intake. PMID:15708486

  7. CCK-8 injected into the nucleus accumbens attenuates the supersensitive locomotor response to apomorphine in 6-OHDA and chronic-neuroleptic treated rats.

    PubMed

    Weiss, F; Ettenberg, A; Koob, G F

    1989-01-01

    Postsynaptic dopamine-cholecystokinin (CCK) interactions in the nucleus accumbens were studied in two behavioral preparations of DA receptor supersensitivity: chronic-neuroleptic treated and 6-hydroxydopamine (6-OHDA) denervated rats. Subcutaneous (SC) injections of apomorphine (APO; 0.15 mg/kg) in experiment 1 produced marked hyperlocomotion in rats following 12 days of pretreatment with cis-[Z]-flupenthixol (2 mg/kg; twice per day). Bilateral intra-accumbens (N.Acc.) microinjections of CCK-8 (2 ng and 2 micrograms) reliably reduced APO-stimulated hyperlocomotion. An intermediate CCK dose (20 ng) was without effect. No change in APO responsivity following chronic vehicle treatment was observed and the baseline APO response was not altered by CCK at any dose. Denervation of mesolimbic dopamine (DA) terminals by intra-N.Acc. injections of 6-hydroxydopamine (6-OHDA; 8 micrograms/side) in experiment 2 similarly resulted in intense locomotor hyperactivity after APO stimulation (0.1 mg/kg; SC). Bilateral intra-N.Acc. injections of CCK-8 (1, 10, 100 ng, and 1 micrograms) significantly attenuated the supersensitive locomotor response to APO. As in experiment 1, CCK produced "biphasic" dose-response effects with strong attenuation that persisted throughout the entire 60-min test at both high (1 microgram) and low (1 ng) doses. Intermediate CCK doses (10 and 100 ng) produced only short-term reductions in activity. Hypomotility induced by APO in SHAM-lesioned rats was not effectively reversed by CCK treatments. CCK had no effect on unstimulated baseline locomotor activity in either 6-OHDA or SHAM-lesioned rats. These results provide further evidence that CCK-8 modulates mesolimbic DA activity by functionally opposing the postsynaptic effects of DA in the region of the nucleus accumbens. PMID:2574480

  8. Hyperglycemia Determines Increased Specific MicroRNAs Levels in Sera and HDL of Acute Coronary Syndrome Patients and Stimulates MicroRNAs Production in Human Macrophages

    PubMed Central

    Carnuta, Mihaela G.; Sanda, Gabriela M.; Stancu, Camelia S.; Popescu, Andreea C.; Popescu, Mihaela R.; Vlad, Adelina; Dimulescu, Doina R.; Simionescu, Maya; Sima, Anca V.

    2016-01-01

    We aimed to determine the levels of microRNAs (miRNAs) in sera and HDL of acute coronary syndrome (ACS) compared to stable angina (SA) patients with/without hyperglycemia, and evaluate comparatively the functional effect of these sera on the processing machinery proteins (Drosha, DGCR8, Dicer) and miRNAs production in human macrophages. MiRNAs levels in sera and HDL from 35 SA and 72 ACS patients and 30 healthy subjects were measured by using microRNA TaqMan assays. MiR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels were higher in the hyperglycemic ACS compared to normoglycemic sera. MiR-223 and miR-486 prevailed in HDL2, while miR-92a predominated in HDL3, all three miRNAs discriminating between ACS and SA patients; their levels were increased in HDL from hyperglycemic ACS patients versus normoglycemic ones. The incubation of human macrophages with sera from ACS and SA patients showed that all patients’ sera induced an increase of Drosha, DGCR8 and Dicer expressions and of selected miRNAs levels compared to control sera, the effect being higher in the case of hyperglycemic versus normoglycemic ACS sera. The addition of glucose to SA and ACS sera increased Drosha, DGCR8 and Dicer expression and miRNAs levels in the exposed macrophages. In conclusion, hyperglycemia is associated with increased miR-223, miR-92a, miR-486 levels in HDL, which discriminate between ACS and SA patients. Exposure of human macrophages to ACS compared to SA sera determines the upregulation of Drosha, DGCR8 and Dicer expression and the increase of selected miRNAs production, the effect being augmented by an increased glucose concentration. PMID:27519051

  9. Hyperglycemia Determines Increased Specific MicroRNAs Levels in Sera and HDL of Acute Coronary Syndrome Patients and Stimulates MicroRNAs Production in Human Macrophages.

    PubMed

    Simionescu, Natalia; Niculescu, Loredan S; Carnuta, Mihaela G; Sanda, Gabriela M; Stancu, Camelia S; Popescu, Andreea C; Popescu, Mihaela R; Vlad, Adelina; Dimulescu, Doina R; Simionescu, Maya; Sima, Anca V

    2016-01-01

    We aimed to determine the levels of microRNAs (miRNAs) in sera and HDL of acute coronary syndrome (ACS) compared to stable angina (SA) patients with/without hyperglycemia, and evaluate comparatively the functional effect of these sera on the processing machinery proteins (Drosha, DGCR8, Dicer) and miRNAs production in human macrophages. MiRNAs levels in sera and HDL from 35 SA and 72 ACS patients and 30 healthy subjects were measured by using microRNA TaqMan assays. MiR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels were higher in the hyperglycemic ACS compared to normoglycemic sera. MiR-223 and miR-486 prevailed in HDL2, while miR-92a predominated in HDL3, all three miRNAs discriminating between ACS and SA patients; their levels were increased in HDL from hyperglycemic ACS patients versus normoglycemic ones. The incubation of human macrophages with sera from ACS and SA patients showed that all patients' sera induced an increase of Drosha, DGCR8 and Dicer expressions and of selected miRNAs levels compared to control sera, the effect being higher in the case of hyperglycemic versus normoglycemic ACS sera. The addition of glucose to SA and ACS sera increased Drosha, DGCR8 and Dicer expression and miRNAs levels in the exposed macrophages. In conclusion, hyperglycemia is associated with increased miR-223, miR-92a, miR-486 levels in HDL, which discriminate between ACS and SA patients. Exposure of human macrophages to ACS compared to SA sera determines the upregulation of Drosha, DGCR8 and Dicer expression and the increase of selected miRNAs production, the effect being augmented by an increased glucose concentration. PMID:27519051

  10. Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

    PubMed Central

    Maron, Bradley A.; Oldham, William M.; Chan, Stephen Y.; Vargas, Sara O.; Arons, Elena; Zhang, Ying-Yi; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    Background The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in PAH. Methods and Results Patients with PAH, rats with Sugen/hypoxia-PAH, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein (AP-1) site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-siRNA or treated with the AP-1 inhibitor, SR-11302, hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro, and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in Conclusions Our findings identify autonomous aldosterone synthesis in HPAECs due to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular

  11. DEVELOPMENT OF LOCOMOTOR ACTIVITY OF RAT PUPS EXPOSED TO HEAVY METALS

    EPA Science Inventory

    Cadmium (Cd), triethyltin (TET), and trimethyltin (TMT) are heavy metals which are neurotoxic to developing animals. In the present experiment, preweaning assessment of locomotor activity was used to detect and differentiate between the developmental toxicity of these metals. On ...

  12. Woodlouse locomotor behavior in the assessment of clean and contaminated field sites

    SciTech Connect

    Bayley, M.; Baatrup, E.; Bjerregaard, P.

    1997-11-01

    Specimens of the woodlouse Oniscus asellus were collected at four clean field sites and from a recently closed iron foundry heavily contaminated with zinc, lead, chromium, and nickel. Each of the 30 woodlice per group was housed individually and acclimatized to laboratory conditions for 2 d on a humid plaster of paris substrate. Thereafter, the locomotor behavior of each animal was measured for 4 h employing automated computer-aided video tracking. Linear discriminant analysis of five locomotor parameters revealed average velocity and path length as the principle components separating the polluted site and control animals. Post hoc analysis of the discriminant variable for animals from all five sites showed that the animals from the polluted site where significantly hyperactive when compared to all controls. Further, control animals collected from sites separated by several hundred kilometers were remarkably similar in their locomotor behavior. This preliminary study highlights the potential utility of quantitative analysis of animal locomotor behavior in environmental monitoring.

  13. IMPORTANCE OF D1 AND D2 RECEPTORS IN THE DORSAL CAUDATE-PUTAMEN FOR THE LOCOMOTOR ACTIVITY AND STEREOTYPED BEHAVIORS OF PREWEANLING RATS

    PubMed Central

    CHARNTIKOV, S.; DER-GHAZARIAN, T.; HERBERT, M. S.; HORN, L. R.; WIDARMA, C. B.; GUTIERREZ, A.; VARELA, F. A.; MCDOUGALL, S. A.

    2011-01-01

    Dopaminergic compounds often affect the unlearned behaviors of preweanling and adult rats differently, although the brain regions underlying these age-dependent behavioral effects have not been specified. A candidate brain region is the dorsal caudate-putamen (CPu); thus, a goal of the present study was to determine whether D1 and D2 receptors in the dorsal CPu are capable of modulating the unlearned behaviors of preweanling rats. In Experiments 1 and 2, selective and nonselective dopamine agonists were bilaterally microinjected into the dorsal CPu on postnatal day (PD) 18 and both locomotor activity and stereotypy were measured. In Experiment 3, the functional coupling of D1 and D2 receptors was assessed by microinjecting the D1 agonist SKF-82958 and the D2/D3 agonist quinpirole either alone or in combination. In Experiments 4 and 5, quinpirole and the D1 receptor antagonist SCH-23390, or SKF-82958 and the D2 receptor antagonist raclopride, were co-administered into the dorsal CPu to further assess whether a functional D1 or D2 receptor system is necessary for the expression of quinpirole- or SKF-82958-induced behaviors. Results showed that selective stimulation of D1 or D2 receptors in the dorsal CPu increased both the locomotor activity and stereotypy of preweanling rats. Receptor coupling was evident on PD 18 because co-administration of a subthreshold dose of SKF-82958 and quinpirole produced more locomotor activity than either agonist alone. Lastly, the dopamine antagonist experiments showed that both D1 and D2 receptor systems must be functional for SKF-82958- or quinpirole-induced locomotor activity to be fully manifested. When the present data are compared to results from non-ontogenetic studies, it appears that pharmacological manipulation of D1 and D2 receptors in the dorsal CPu affects the behavior of preweanling and adult rats in a generally similar manner, although some important age-dependent differences are apparent. For example, D1 and/or D2

  14. Importance of D1 and D2 receptors in the dorsal caudate-putamen for the locomotor activity and stereotyped behaviors of preweanling rats.

    PubMed

    Charntikov, S; Der-Ghazarian, T; Herbert, M S; Horn, L R; Widarma, C B; Gutierrez, A; Varela, F A; McDougall, S A

    2011-06-01

    Dopaminergic compounds often affect the unlearned behaviors of preweanling and adult rats differently, although the brain regions underlying these age-dependent behavioral effects have not been specified. A candidate brain region is the dorsal caudate-putamen (CPu); thus, a goal of the present study was to determine whether D1 and D2 receptors in the dorsal CPu are capable of modulating the unlearned behaviors of preweanling rats. In Experiments 1 and 2, selective and nonselective dopamine agonists were bilaterally microinjected into the dorsal CPu on postnatal day (PD) 18 and both locomotor activity and stereotypy were measured. In Experiment 3, the functional coupling of D1 and D2 receptors was assessed by microinjecting the D1 agonist SKF-82958 and the D₂/D₃ agonist quinpirole either alone or in combination. In Experiments 4 and 5, quinpirole and the D1 receptor antagonist SCH-23390, or SKF-82958 and the D2 receptor antagonist raclopride, were co-administered into the dorsal CPu to further assess whether a functional D1 or D2 receptor system is necessary for the expression of quinpirole- or SKF-82958-induced behaviors. Results showed that selective stimulation of D1 or D2 receptors in the dorsal CPu increased both the locomotor activity and stereotypy of preweanling rats. Receptor coupling was evident on PD 18 because co-administration of a subthreshold dose of SKF-82958 and quinpirole produced more locomotor activity than either agonist alone. Lastly, the dopamine antagonist experiments showed that both D1 and D2 receptor systems must be functional for SKF-82958- or quinpirole-induced locomotor activity to be fully manifested. When the present data are compared to results from non-ontogenetic studies, it appears that pharmacological manipulation of D1 and D2 receptors in the dorsal CPu affects the behavior of preweanling and adult rats in a generally similar manner, although some important age-dependent differences are apparent. For example, D1 and/or D2

  15. Risperidone alters food intake, core body temperature, and locomotor activity in mice

    PubMed Central

    Cope, Mark B.; Li, Xingsheng; Jumbo-Lucioni, Patricia; DiCostanzo, Catherine A.; Jamison, Wendi G.; Kesterson, Robert A.; Allison, David B.; Nagy, Tim R.

    2009-01-01

    Risperidone induces significant weight gain in female mice; however, the underlying mechanisms related to this effect are unknown. We investigated the effects of risperidone on locomotor activity, core body temperature, and uncoupling protein (UCP) and hypothalamic orexin mRNA expression. Female C57BL/6J mice were acclimated to individual housing and randomly assigned to either risperidone (4 mg/kg BW*day) or placebo (PLA). Activity and body temperature were measured over 48-hour periods twice a week for 3 weeks. Food intake and body weights were measured weekly. UCP1 (BAT), UCP3 (gastrocnemius), and orexin (hypothalamus) mRNA expressions were measured using RT-PCR. Risperidone-treated mice consumed more food (p=0.050) and gained more weight (p=0.0001) than PLA-treated mice after 3 weeks. During the initial 2-days of treatment, there was an acute effect of treatment on activity (p=0.046), but not body temperature (p=0.290). During 3 weeks of treatment, average core body temperatures were higher in risperidone-treated mice compared to controls during the light phase (p=0.0001), and tended to be higher during the dark phase (p=0.057). Risperidone-treated mice exhibited lower activity levels than controls during the dark phase (p=0.006); there were no differences in activity during the light phase (p=0.47). UCP1 (p<0.01) and UCP3 (p<0.05) mRNA expressions were greater in risperidone-treated mice compared to controls, whereas, orexin mRNA expression was lower in risperidone-treated mice (p<0.01). These results suggest that risperidone-induced weight gain in mice is a consequence of increased energy intake and reduced activity, while the elevation in body temperature may be a result of thermogenic effect of food intake and elevated UCP1, UCP3, and a reduced hypothalamic orexin expression. PMID:19084548

  16. Intranasal haloperidol-loaded miniemulsions for brain targeting: Evaluation of locomotor suppression and in-vivo biodistribution.

    PubMed

    El-Setouhy, Doaa Ahmed; Ibrahim, A B; Amin, Maha M; Khowessah, Omneya M; Elzanfaly, Eman S

    2016-09-20

    Haloperidol is a commonly prescribed antipsychotic drug currently administered as oral and injectable preparations. This study aimed to prepare haloperidol intranasal miniemulsion helpful for psychiatric emergencies and exhibiting lower systemic exposure and side effects associated with non-target site delivery. Haloperidol miniemulsions were successfully prepared by spontaneous emulsification adopting 2(3) factorial design. The effect of three independent variables at two levels each namely; oil type (Capmul®-Capryol™90), lipophilic emulsifier type (Span 20-Span 80) and HLB value (12-14) on globule size, PDI and percent locomotor activity inhibition in mice was evaluated. The optimized formula (F4, Capmul®, Tween 80/Span 20, HLB 14) showed globule size of 209.5±0.98nm, PDI of 0.402±0.03 and locomotor inhibition of 83.89±9.15% with desirability of 0.907. Biodistribution study following intranasal and intravenous administration of the radiolabeled (99m)Tc mucoadhesive F4 revealed that intranasal administration achieved 1.72-fold higher and 6 times faster peak brain levels compared with intravenous administration. Drug targeting efficiency percent and brain/blood exposure ratios remained above 100% and 1 respectively after intranasal instillation compared to a maximum brain/blood exposure ratio of 0.8 post intravenous route. Results suggested the CNS delivery of major fraction of haloperidol via direct transnasal to brain pathway that can be a promising alternative to oral and parenteral routes in chronic and acute situations. Haloperidol concentration of 275.6ng/g brain 8h post intranasal instillation, higher than therapeutic concentration range of haloperidol (0.8 to 5.15ng/ml), suggests possible sustained delivery of the drug through nasal route. PMID:27154259

  17. Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue

    PubMed Central

    Rosas, Odrick R.; Torrado, Aranza I.; Santiago, Jose M.; Rodriguez, Ana E.; Salgado, Iris K.; Miranda, Jorge D.

    2014-01-01

    The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine (PP2), a selective SFK inhibitor, after spinal cord contusion with the New York University (NYU) impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-injury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin (a guanine nucleotide exchange factor) phosphorylation in the acute phase (4 days post-injury) after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexin1 phosphorylation (activation) by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury. PMID:25657738

  18. Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue.

    PubMed

    Rosas, Odrick R; Torrado, Aranza I; Santiago, Jose M; Rodriguez, Ana E; Salgado, Iris K; Miranda, Jorge D

    2014-12-15

    The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase (SFK) activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine (PP2), a selective SFK inhibitor, after spinal cord contusion with the New York University (NYU) impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-injury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin (a guanine nucleotide exchange factor) phosphorylation in the acute phase (4 days post-injury) after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexin1 phosphorylation (activation) by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury. PMID:25657738

  19. Involvement of nigral oxytocin in locomotor activity: A behavioral, immunohistochemical and lesion study in male rats.

    PubMed

    Angioni, Laura; Cocco, Cristina; Ferri, Gian-Luca; Argiolas, Antonio; Melis, Maria Rosaria; Sanna, Fabrizio

    2016-07-01

    Oxytocin is involved in the control of different behaviors, from sexual behavior and food consumption to empathy, social and affective behaviors. An imbalance of central oxytocinergic neurotransmission has been also associated with different mental pathologies, from depression, anxiety and anorexia/bulimia to schizophrenia, autism and drug dependence. This study shows that oxytocin may also play a role in the control of locomotor activity. Accordingly, intraperitoneal oxytocin (0.5-2000μg/kg) reduced locomotor activity of adult male rats. This effect was abolished by d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist, given into the lateral ventricles at the dose of 2μg/rat, which was ineffective on locomotor activity. Oxytocin (50-200ng/site) also reduced and d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (2μg/site) increased locomotor activity when injected bilaterally into the substantia nigra, a key area in the control of locomotor activity. Conversely, the destruction of nigral neurons bearing oxytocin receptors by the recently characterized neurotoxin oxytocin-saporin injected into the substantia nigra, increased basal locomotor activity. Since oxytocin-saporin injected into the substantia nigra caused a marked reduction of neurons immunoreactive for tyrosine hydroxylase (e.g., nigrostriatal dopaminergic neurons) and for vesicular glutamate transporters VGluT1, VGluT2 and VGluT3 (e.g., glutamatergic neurons), but not for glutamic acid decarboxylase (e.g., GABAergic neurons), together these findings suggest that oxytocin influences locomotor activity by acting on receptors localized presynaptically in nigral glutamatergic nerve terminals (which control the activity of nigral GABAergic efferent neurons projecting to brain stem nuclei controlling locomotor activity), rather than on receptors localized in the cell bodies/dendrites of nigrostriatal dopaminergic neurons. PMID:27189764

  20. Locomotor behavior of fish hatched from embryos exposed to flight conditions

    NASA Technical Reports Server (NTRS)

    Kleerekoper, H.

    1978-01-01

    Embryos of Fundulus heteroclitus in various stages of development were exposed to space flight conditions aboard Apollo spacecraft and Cosmos satellites. The objective of the study was to ascertain whether fish hatched from these embryos displayed locomotor behavior different from that of control fish of the same age. An electronic monitoring technique was used to record behavior. Results indicate no change in locomotor behavior in fish on Apollo Spacecraft, but inexplicable significant changes were noted in fish aboard Cosmos Satellites.

  1. R7BP Complexes With RGS9-2 and RGS7 in the Striatum Differentially Control Motor Learning and Locomotor Responses to Cocaine

    PubMed Central

    Anderson, Garret R; Cao, Yan; Davidson, Steve; Truong, Hai V; Pravetoni, Marco; Thomas, Mark J; Wickman, Kevin; Giesler, Glenn J; Martemyanov, Kirill A

    2010-01-01

    In the striatum, signaling through G protein-coupled dopamine receptors mediates motor and reward behavior, and underlies the effects of addictive drugs. The extent of receptor responses is determined by RGS9-2/Gβ5 complexes, a striatally enriched regulator that limits the lifetime of activated G proteins. Recent studies suggest that the function of RGS9-2/Gβ5 is controlled by the association with an additional subunit, R7BP, making elucidation of its contribution to striatal signaling essential for understanding molecular mechanisms of behaviors mediated by the striatum. In this study, we report that elimination of R7BP in mice results in motor coordination deficits and greater locomotor response to morphine administration, consistent with the essential role of R7BP in maintaining RGS9-2 expression in the striatum. However, in contrast to previously reported observations with RGS9-2 knockouts, mice lacking R7BP do not show higher sensitivity to locomotor-stimulating effects of cocaine. Using a striatum-specific knockdown approach, we show that the sensitivity of motor stimulation to cocaine is instead dependent on RGS7, whose complex formation with R7BP is dictated by RGS9-2 expression. These results indicate that dopamine signaling in the striatum is controlled by concerted interplay between two RGS proteins, RGS7 and RGS9-2, which are balanced by a common subunit, R7BP. PMID:20043004

  2. A Combined Robotic and Cognitive Training for Locomotor Rehabilitation: Evidences of Cerebral Functional Reorganization in Two Chronic Traumatic Brain Injured Patients

    PubMed Central

    Sacco, Katiuscia; Cauda, Franco; D’Agata, Federico; Duca, Sergio; Zettin, Marina; Virgilio, Roberta; Nascimbeni, Alberto; Belforte, Guido; Eula, Gabriella; Gastaldi, Laura; Appendino, Silvia; Geminiani, Giuliano

    2011-01-01

    It has been demonstrated that automated locomotor training can improve walking capabilities in spinal cord-injured subjects but its effectiveness on brain damaged patients has not been well established. A possible explanation of the discordant results on the efficacy of robotic training in patients with cerebral lesions could be that these patients, besides stimulation of physiological motor patterns through passive leg movements, also need to train the cognitive aspects of motor control. Indeed, another way to stimulate cerebral motor areas in paretic patients is to use the cognitive function of motor imagery. A promising possibility is thus to combine sensorimotor training with the use of motor imagery. The aim of this paper is to assess changes in brain activations after a combined sensorimotor and cognitive training for gait rehabilitation. The protocol consisted of the integrated use of a robotic gait orthosis prototype with locomotor imagery tasks. Assessment was conducted on two patients with chronic traumatic brain injury and major gait impairments, using functional magnetic resonance imaging. Physiatric functional scales were used to assess clinical outcomes. Results showed greater activation post-training in the sensorimotor and supplementary motor cortices, as well as enhanced functional connectivity within the motor network. Improvements in balance and, to a lesser extent, in gait outcomes were also found. PMID:22275890

  3. Rotenone-stimulated superoxide release from mitochondrial complex I acutely augments L-type Ca2+ current in A7r5 aortic smooth muscle cells.

    PubMed

    Ochi, Rikuo; Dhagia, Vidhi; Lakhkar, Anand; Patel, Dhara; Wolin, Michael S; Gupte, Sachin A

    2016-05-01

    Voltage-gated L-type Ca(2+) current (ICa,L) induces contraction of arterial smooth muscle cells (ASMCs), and ICa,L is increased by H2O2 in ASMCs. Superoxide released from the mitochondrial respiratory chain (MRC) is dismutated to H2O2 We studied whether superoxide per se acutely modulates ICa,L in ASMCs using cultured A7r5 cells derived from rat aorta. Rotenone is a toxin that inhibits complex I of the MRC and increases mitochondrial superoxide release. The superoxide content of mitochondria was estimated using mitochondrial-specific MitoSOX and HPLC methods, and was shown to be increased by a brief exposure to 10 μM rotenone. ICa,L was recorded with 5 mM BAPTA in the pipette solution. Rotenone administration (10 nM to 10 μM) resulted in a greater ICa,L increase in a dose-dependent manner to a maximum of 22.1% at 10 μM for 1 min, which gradually decreased to 9% after 5 min. The rotenone-induced ICa,L increase was associated with a shift in the current-voltage relationship (I-V) to a hyperpolarizing direction. DTT administration resulted in a 17.9% increase in ICa,L without a negative shift in I-V, and rotenone produced an additional increase with a shift. H2O2 (0.3 mM) inhibited ICa,L by 13%, and additional rotenone induced an increase with a negative shift. Sustained treatment with Tempol (4-hydroxy tempo) led to a significant ICa,L increase but it inhibited the rotenone-induced increase. Staurosporine, a broad-spectrum protein kinase inhibitor, partially inhibited ICa,L and completely suppressed the rotenone-induced increase. Superoxide released from mitochondria affected protein kinases and resulted in stronger ICa,L preceding its dismutation to H2O2 The removal of nitric oxide is a likely mechanism for the increase in ICa,L. PMID:26873970

  4. Reconstructing the locomotor repertoire of Protopithecus brasiliensis. I. Body size.

    PubMed

    Halenar, Lauren B

    2011-12-01

    An accurate body size estimate is essential for reconstructing and interpreting many aspects of the paleobiology of an extinct taxon. With this in mind, the purpose of this study is two-fold: first, to create statistically robust predictive regression equations for body mass, total body length, and head and body length from postcranial elements using a platyrrhine reference sample, data that do not exist elsewhere in the literature; and, second, to apply those regression equations to the "giant" subfossil platyrrhine Protopithecus brasiliensis, a little-studied taxon represented by a nearly complete skeleton. Building on results of previous work with other primate groups, different skeletal elements, subgroups of the reference sample, and regression models lead to different body size estimates with different standard errors and prediction errors. However, relatively tight clusters of estimates around 20 kg, total length of 1,675 mm, and head and body length of 710 mm are obtained, placing the fossil in the size range of a large male baboon. While not quite as large as the original 25 kg body mass estimate for the fossil, this new estimate is still approximately 150% larger than the largest living New World monkey. Confirmation of its place in a large-bodied size class of platyrrhines has a profound effect on reconstructing the locomotor repertoire of Protopithecus and the evolutionary trajectory of the alouattin lineage. PMID:22042663

  5. Locomotor head movements and semicircular canal morphology in primates

    PubMed Central

    Malinzak, Michael D.; Kay, Richard F.; Hullar, Timothy E.

    2012-01-01

    Animal locomotion causes head rotations, which are detected by the semicircular canals of the inner ear. Morphologic features of the canals influence rotational sensitivity, and so it is hypothesized that locomotion and canal morphology are functionally related. Most prior research has compared subjective assessments of animal “agility” with a single determinant of rotational sensitivity: the mean canal radius of curvature (R). In fact, the paired variables of R and body mass are correlated with agility and have been used to infer locomotion in extinct species. To refine models of canal functional morphology and to improve locomotor inferences for extinct species, we compare 3D vector measurements of head rotation during locomotion with 3D vector measures of canal sensitivity. Contrary to the predictions of conventional models that are based upon R, we find that axes of rapid head rotation are not aligned with axes of either high or low sensitivity. Instead, animals with fast head rotations have similar sensitivities in all directions, which they achieve by orienting the three canals of each ear orthogonally (i.e., along planes at 90° angles to one another). The extent to which the canal configuration approaches orthogonality is correlated with rotational head speed independent of body mass and phylogeny, whereas R is not. PMID:23045679

  6. Sex differences in Siberian hamster ultradian locomotor rhythms.

    PubMed

    Prendergast, Brian J; Stevenson, Tyler J; Zucker, Irving

    2013-02-17

    Sex differences in ultradian activity rhythms (URs) and circadian rhythms (CRs) were assessed in Siberian hamsters kept in long day (LD) or short day (SD) photoperiods for 40 weeks. For both sexes URs of locomotor activity were more prevalent, greater in amplitude and more robust in SDs. The UR period was longer in females than males in both day lengths. The reproductive system underwent regression and body mass declined during the initial 10 weeks of SD treatment, and in both sexes these traits spontaneously reverted to the LD phenotype at or before 40 weeks in SD, reflecting the development of neuroendocrine refractoriness to SD patterns of melatonin secretion. Hamsters of both sexes, however, continued to display SD-like URs at the 40 weeks time point. CRs were less prevalent and the waveform less robust and lower in amplitude in SDs than LDs; the SD circadian waveform also did not revert to the long-day phenotype after 40 weeks of SD treatment. Short day lengths enhanced ultradian and diminished circadian rhythms in both sexes. Day length controls several UR characteristics via gonadal steroid and melatonin-independent mechanisms. Sex differences in ultradian timing may contribute to sex diphenisms in rhythms of sleep, food intake and exercise. PMID:23333554

  7. Human pendulum approach to simulate and quantify locomotor impact loading.

    PubMed

    Lafortune, M A; Lake, M J

    1995-09-01

    The understanding of impact mechanics during locomotion is important for research within the fields of injury prevention and footwear design. Instrumented missiles offer a worthy solution to the lack of control inherent in in vivo activities and to the isolated nature of tissue studies. However, missiles cannot mimic the magnitude and temporal characteristics of locomotion impacts. A human pendulum approach employed the subject's own body as the missile to impart controlled impacts to the lower extremity. The subject is swung toward a force platform instrumented wall while lying supine on a suspended lightweight bed. The ability of the pendulum to reproduce locomotor impact loading was assessed for heel-toe running. Axial reaction force and shank acceleration patterns recorded during pendulum tests in ten subjects were found to closely resemble running patterns and they were obtained without discomfort to the subjects. This new approach relies upon one's own body to impart impacts representative of locomotion. It should prove useful to study human impact loading in a controlled manner. PMID:7559680

  8. Effects of captivity and body condition on plasma corticosterone, locomotor behavior, and plasma metabolites in curve-billed thrashers.

    PubMed

    Fokidis, H Bobby; Hurley, Laura; Rogowski, Christopher; Sweazea, Karen; Deviche, Pierre

    2011-01-01

    The acute stress response involves the secretion of catabolic glucocorticoids, such as corticosterone (CORT) in birds, that mobilize intrinsic energy stores primarily through a gluconeogenic pathway involving fat breakdown, thus linking body condition and stress. We measured changes in CORT and gluconeogenic metabolites (triglycerides, free glycerols, glucose) during handling stress in curve-billed thrashers Toxostoma curvirostre from two habitats (urban vs. desert) that may differ in food abundance in the wild, in captivity, and in response to both food restriction and subsequent recovery. Urban thrashers were heavier and secreted more CORT than desert birds in the field, but differences did not persist in captivity. Decreased access to food resulted in decreased body mass and a diminished ability to elevate plasma CORT in response to handling stress. However, the opposite effect was observed as these birds recovered from food restriction. Plasma levels of glucose and triglycerides did not change with stress. Food restriction also increased locomotor activity, which likely further exacerbated energy loss. These observations suggest that body condition and stress differences between urban and desert birds may be related to differences in their relative energetic states, possibly due to food availability. Body condition may affect the extent to which an individual can elevate CORT and use free glycerol as energy during acute stress. PMID:22030852

  9. Effects of sex pheromones and sexual maturation on locomotor activity in female sea lamprey (Petromyzon marinus).

    PubMed

    Walaszczyk, Erin J; Johnson, Nicholas S; Steibel, Juan Pedro; Li, Weiming

    2013-06-01

    Synchronization of male and female locomotor rhythmicity can play a vital role in ensuring reproductive success. Several physiological and environmental factors alter these locomotor rhythms. As sea lamprey, Petromyzon marinus, progress through their life cycle, their locomotor activity rhythm changes multiple times. The goal of this study was to elucidate the activity patterns of adult female sea lamprey during the sexual maturation process and discern the interactions of these patterns with exposure to male pheromones. During these stages, preovulated and ovulated adult females are exposed to sex pheromone compounds, which are released by spermiated males and attract ovulated females to the nest for spawning. The locomotor behavior of adult females was monitored in a natural stream with a passive integrated tag responder system as they matured, and they were exposed to a sex pheromone treatment (spermiated male washings) or a control (prespermiated male washings). Results showed that, dependent on the hour of day, male sex pheromone compounds reduce total activity (p < 0.05) and cause increases in activity during several daytime hours in preovulated and ovulated females. These results are one of the first examples of how sex pheromones modulate a locomotor rhythm in a vertebrate, and they suggest that the interaction between maturity stage and sex pheromone exposure contributes to the differential locomotor rhythms found in adult female sea lamprey. This phenomenon may contribute to the reproductive synchrony of mature adults, thus increasing reproductive success in this species. PMID:23735501

  10. Effects of sex pheromones and sexual maturation on locomotor activity in female sea lamprey (Petromyzon marinus)

    USGS Publications Warehouse

    Walaszczyk, Erin J.; Johnson, Nicholas S.; Steibel, Juan Pedro; Li, Weiming

    2013-01-01

    Synchronization of male and female locomotor rhythmicity can play a vital role in ensuring reproductive success. Several physiological and environmental factors alter these locomotor rhythms. As sea lamprey, Petromyzon marinus, progress through their life cycle, their locomotor activity rhythm changes multiple times. The goal of this study was to elucidate the activity patterns of adult female sea lamprey during the sexual maturation process and discern the interactions of these patterns with exposure to male pheromones. During these stages, preovulated and ovulated adult females are exposed to sex pheromone compounds, which are released by spermiated males and attract ovulated females to the nest for spawning. The locomotor behavior of adult females was monitored in a natural stream with a passive integrated tag responder system as they matured, and they were exposed to a sex pheromone treatment (spermiated male washings) or a control (prespermiated male washings). Results showed that, dependent on the hour of day, male sex pheromone compounds reduce total activity (p < 0.05) and cause increases in activity during several daytime hours in preovulated and ovulated females. These results are one of the first examples of how sex pheromones modulate a locomotor rhythm in a vertebrate, and they suggest that the interaction between maturity stage and sex pheromone exposure contributes to the differential locomotor rhythms found in adult female sea lamprey. This phenomenon may contribute to the reproductive synchrony of mature adults, thus increasing reproductive success in this species.

  11. Seasonality in circadian locomotor activity and serum testosterone level in the subtropical tree sparrow (Passer montanus).

    PubMed

    Dixit, Anand S; Singh, Namram S

    2016-05-01

    Seasonality in daily locomotor activity pattern was investigated in the subtropical tree sparrow by exposing a group of birds to natural day lengths (NDL) for 30days and another group to 12L/12D for 14days followed by transfer to constant dim light (LLdim) for another 15days in four different seasons of the year. Serum testosterone levels were also measured during different seasons. Sparrows, under NDL, exhibited distinct circadian rhythmicity in their locomotor activity with almost similar general pattern in different seasons that restricted mainly to the light hours. However, they showed season-dependent differences in the characteristics of circadian locomotor activity rhythm. Birds, when exposed to 12L/12D, showed entrainment of their locomotor activity rhythm with the activity confined mainly during the light phase. Though, tau (τ) under free run conditions did not show any significant difference, the activity period varied significantly in different seasons. The highest level of testosterone was recorded in the spring season that corresponded with the maximum locomotor activity in spring months. The seasonality in daily locomotor activity correlates with the seasonal changes in testosterone levels suggesting the influence of gonadal steroids on endogenous circadian system which is indicative of adaptation of tree sparrow to local photoperiodic conditions. PMID:26945648

  12. Locomotor, feeding and melatonin daily rhythms in sharpsnout seabream (Diplodus puntazzo).

    PubMed

    Vera, L M; Madrid, J A; Sánchez-Vázquez, F J

    2006-06-15

    Sharpsnout seabream is a marine teleost of increasing interest for Mediterranean aquaculture, but there is still a lack of information regarding its circadian organization. In this study, we have investigated sharpsnout seabream locomotor activity, feeding and plasma melatonin daily rhythms under a 12:12-h LD cycle, as well as the persistence of locomotor activity circadian rhythmicity under constant light (LL) conditions. When submitted to an LD cycle, most sharpsnout seabream displayed a diurnal locomotor pattern, with an average 74% of activity recorded during daytime. However, along the experiment 40% of fish spontaneously changed their locomotor rhythm phasing and became nocturnal. Feeding behaviour, nevertheless, remained strictly diurnal in all cases, with 97% of food demands being made during the light period. Free-running locomotor rhythms were recorded in one third of the fish kept under LL. Daily plasma melatonin levels displayed a rhythmic profile, with low daytime values (111 pg/ml) and high nighttime concentrations (791 pg/ml). Taken together, these results evidence a high degree of plasticity for sharpsnout seabream activity patterns, as well as phasing independence of locomotor and feeding rhythms. Finally, the existence of a well-defined daily rhythm of plasma melatonin was found. PMID:16682061

  13. Establishment of a retinoic acid-resistant human acute promyelocytic leukaemia (APL) model in human granulocyte-macrophage colony-stimulating factor (hGM-CSF) transgenic severe combined immunodeficiency (SCID) mice.

    PubMed Central

    Fukuchi, Y.; Kizaki, M.; Kinjo, K.; Awaya, N.; Muto, A.; Ito, M.; Kawai, Y.; Umezawa, A.; Hata, J.; Ueyama, Y.; Ikeda, Y.

    1998-01-01

    To understand the mechanisms and identify novel approaches to overcoming retinoic acid (RA) resistance in acute promyelocytic leukaemia (APL), we established the first human RA-resistant APL model in severe combined immunodeficiency (SCID) mice. UF-1 cells, an RA-resistant APL cell line established in our laboratory, were transplanted into human granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing SCID (hGMTg SCID) mice and inoculated cells formed subcutaneous tumours in all hGMTg SCID mice, but not in the non-transgenic control SCID mice. Single-cell suspensions (UF-1/GMTg SCID cells) were similar in morphological, immunological, cytogenetic and molecular genetic features to parental UF-1 cells. All-trans RA did not change the morphological features of cells or their expression of CD11b. RA did not alter the growth curve of cells as determined by MTT assay, suggesting that UF-1/GMTg SCID cells are resistant to RA. These results demonstrate that this is the first RA-resistant APL animal model that may be useful for investigating the biology of this myeloid leukaemia in vivo, as well as for evaluating novel therapeutic approaches including patients with RA-resistant APL. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9764578

  14. A low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming regimen versus a daunorubicin plus cytarabine regimen as induction therapy for older patients with acute myeloid leukemia: A propensity score analysis.

    PubMed

    Minakata, Daisuke; Fujiwara, Shin-Ichiro; Ito, Shoko; Mashima, Kiyomi; Umino, Kento; Nakano, Hirofumi; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamasaki, Ryoko; Yamamoto, Chihiro; Ashizawa, Masahiro; Hatano, Kaoru; Okazuka, Kiyoshi; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Muroi, Kazuo; Kanda, Yoshinobu

    2016-03-01

    This retrospective analysis compared the efficacy of intensive induction therapy consisting of daunorubicin and cytarabine (DNR-AraC) to that of less-intensive therapy including low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming (CAG). Patients aged 60 years or older who were newly diagnosed as acute myeloid leukemia (AML) were analyzed. Sixty-four and 48 patients were treated with DNR-AraC and CAG, respectively. The complete remission rates, 3-year overall survival and event-free survival in the DNR-AraC group were significantly superior to those in the CAG group (65.6% vs. 29.2%, p<0.001, 38.4% vs. 12.3%, p=0.0033, and 20.3% vs. 7.8%, p=0.0030, respectively), although these differences were not statistically significant in multivariate analyses. Next, we calculated a propensity score for selecting the CAG regimen from six factors. The DNR-AraC regimen was associated with better survival than the CAG regimen in a low propensity score group, but there was no difference in survival between regimens in a high propensity score group. Intensive therapy should be performed for patients with sufficient general and comorbid conditions, but less-intensive therapy may be sufficient for patients with higher age, myelodysplasia-related changes, and lower white blood cell counts, which were relevant factors in the propensity score calculation. PMID:26790727

  15. ROCK1 in AgRP Neurons Regulates Energy Expenditure and Locomotor Activity in Male Mice

    PubMed Central

    Huang, Hu; Lee, Seung Hwan; Ye, Chianping; Lima, Ines S.; Oh, Byung-Chul; Lowell, Bradford B.; Zabolotny, Janice M.

    2013-01-01

    Normal leptin signaling is essential for the maintenance of body weight homeostasis. Proopiomelanocortin- and agouti-related peptide (AgRP)-producing neurons play critical roles in regulating energy metabolism. Our recent work demonstrates that deletion of Rho-kinase 1 (ROCK1) in the AgRP neurons of mice increased body weight and adiposity. Here, we report that selective loss of ROCK1 in AgRP neurons caused a significant decrease in energy expenditure and locomotor activity of mice. These effects were independent of any change in food intake. Furthermore, AgRP neuron-specific ROCK1-deficient mice displayed central leptin resistance, as evidenced by impaired Signal Transducer and Activator of Transcription 3 activation in response to leptin administration. Leptin's ability to hyperpolarize and decrease firing rate of AgRP neurons was also abolished in the absence of ROCK1. Moreover, diet-induced and genetic forms of obesity resulted in reduced ROCK1 activity in murine arcuate nucleus. Of note, high-fat diet also impaired leptin-stimulated ROCK1 activity in arcuate nucleus, suggesting that a defect in hypothalamic ROCK1 activity may contribute to the pathogenesis of central leptin resistance in obesity. Together, these data demonstrate that ROCK1 activation in hypothalamic AgRP neurons is required for the homeostatic regulation of energy expenditure and adiposity. These results further support previous work identifying ROCK1 as a key regulator of energy balance and suggest that targeting ROCK1 in the hypothalamus may lead to development of antiobesity therapeutics. PMID:23885017

  16. Repeated exposure to the herbicide atrazine alters locomotor activity and the nigrostriatal dopaminergic system of the albino rat.

    PubMed

    Rodríguez, Verónica M; Limón-Pacheco, Jorge H; Mendoza-Trejo, Maria Soledad; González-Gallardo, Adriana; Hernández-Plata, Isela; Giordano, Magda

    2013-01-01

    Atrazine (ATR) is used as a pre- and post-emergent herbicide; although banned in several countries of the European Community, it is still used extensively around the world. A recent study in rats has shown that chronic, daily exposure to 10 mg ATR/kg BW causes hyperactivity, disrupts motor coordination and learning of behavioral tasks, and decreases dopamine levels in the brain. In order to evaluate the short-term effect of ATR exposure on locomotor activity, monoamine markers, and antioxidants, adult male Sprague-Dawley rats received six IP injections of 100 mg ATR/kg BW or vehicle over two weeks. After every ATR injection we found hypoactivity that lasted up to five days, and it was accompanied by reductions in levels of striatal DA, DOPAC, and HVA without any alteration in the striatal expression of the mRNAs for Mn-SOD, Trx-1, DAR-D(1), or DAR-D(2). In contrast, in the nucleus accumbens no changes in monoamine markers were observed, and a down-regulation of Trx-1 expression was detected shortly after the ATR treatment. Moreover, in the ventral midbrain, we found that ATR induced a down-regulation of mRNA for Th and DAT, but it increased VMAT2 mRNA expression. Decreases of monoamine levels and of locomotor activity disappeared three months after ATR treatment; however, an amphetamine challenge (1 mg/kg) given two months after the ATR treatment resulted in a significant stimulation in the exposed group, revealing hidden effects of ATR on dopaminergic systems. These results indicate that ATR exposure differentially modifies the dopaminergic systems, and these modifications may underlie the behavioral changes observed. PMID:23123945

  17. Transcutaneous electrical spinal-cord stimulation in humans

    PubMed Central

    Gerasimenko, Yury; Gorodnichev, Ruslan; Moshonkina, Tatiana; Sayenko, Dimitry; Gad, Parag; Edgerton, V. Reggie

    2016-01-01

    Locomotor behavior is controlled by specific neural circuits called central pattern generators primarily located at the lumbosacral spinal cord. These locomotor-related neuronal circuits have a high level of automaticity; that is, they can produce a “stepping” movement pattern also seen on electromyography (EMG) in the absence of supraspinal and/or peripheral afferent inputs. These circuits can be modulated by epidural spinal-cord stimulation and/or pharmacological intervention. Such interventions have been used to neuromodulate the neuronal circuits in patients with motor-complete spinal-cord injury (SCI) to facilitate postural and locomotor adjustments and to regain voluntary motor control. Here, we describe a novel non-invasive stimulation strategy of painless transcutaneous electrical enabling motor control (pcEmc) to neuromodulate the physiological state of the spinal cord. The technique can facilitate a stepping performance in non-injured subjects with legs placed in a gravity-neutral position. The stepping movements were induced more effectively with multi-site than single-site spinal-cord stimulation. From these results, a multielectrode surface array technology was developed. Our preliminary data indicate that use of the multielectrode surface array can fine-tune the control of the locomotor behavior. As well, the pcEmc strategy combined with exoskeleton technology is effective for improving motor function in paralyzed patients with SCI. The potential impact of using pcEmc to neuromodulate the spinal circuitry has significant implications for furthering our understanding of the mechanisms controlling locomotion and for rehabilitating sensorimotor function even after severe SCI. PMID:26205686

  18. Locomotor disability: meaning, causes and effects of interventions.

    PubMed

    Ebrahim, Shah; Adamson, Joy; Ayis, Salma; Beswick, Andrew; Gooberman-Hill, Rachael

    2008-10-01

    This paper provides a synopsis of a long-term programme of MRC-funded work on locomotor disability in older people. Specifically it describes the meaning and experience of disability, examines the risk factors for disability and systematically reviews the evidence from randomized trials of complex interventions for disability. We undertook a national prospective study of a representative sample of 999 people aged 65 years or more plus in-depth interviews with a small subsample and a selected sample obtained from hospital sources. Secondary analysis of several large prospective studies was carried out and a systematic review and meta-analysis of published randomized controlled trials of the effects of complex interventions for disability. Very few participants subscribed to the constructs of longstanding illness, disability or infirmity that surveys often use. A wide range of social and psychological factors, independently of chronic diseases, were strongly associated with disability. People with greater functional reserve capacity and those with greater self-efficacy were generally less likely to suffer from catastrophic decline in ability and had better quality of life in the face of disability. In reviewing 89 trials (over 97,000 participants) of complex interventions for disability, evidence of benefits was found although no relationship with intensity of intervention was apparent. Our findings on the meaning and experience of disability suggest the need for modifications to routinely used survey questions and for different ways of understanding the need for and receipt of care among older people with disabilities. The diverse risk factors for disability suggest that novel approaches across social, psychological as well as more traditional rehabilitation and behavioural risk factor modification would be worth exploring. Complex interventions appeared to help older people to live independently and limit functional decline irrespective of age and health status

  19. General and Specific Strategies Used to Facilitate Locomotor Maneuvers

    PubMed Central

    Wu, Mengnan; Matsubara, Jesse H.; Gordon, Keith E.

    2015-01-01

    People make anticipatory changes in gait patterns prior to initiating a rapid change of direction. How they prepare will change based on their knowledge of the maneuver. To investigate specific and general strategies used to facilitate locomotor maneuvers, we manipulated subjects’ ability to anticipate the direction of an upcoming lateral “lane-change” maneuver. To examine specific anticipatory adjustments, we observed the four steps immediately preceding a maneuver that subjects were instructed to perform at a known time in a known direction. We hypothesized that to facilitate a specific change of direction, subjects would proactively decrease margin of stability in the future direction of travel. Our results support this hypothesis: subjects significantly decreased lateral margin of stability by 69% on the side ipsilateral to the maneuver during only the step immediately preceding the maneuver. This gait adaptation may have improved energetic efficiency and simplified the control of the maneuver. To examine general anticipatory adjustments, we observed the two steps immediately preceding the instant when subjects received information about the direction of the maneuver. When the maneuver direction was unknown, we hypothesized that subjects would make general anticipatory adjustments that would improve their ability to actively initiate a maneuver in multiple directions. This second hypothesis was partially supported as subjects increased step width and stance phase hip flexion during these anticipatory steps. These modifications may have improved subjects’ ability to generate forces in multiple directions and maintain equilibrium during the onset and execution of the rapid maneuver. However, adapting these general anticipatory strategies likely incurred an additional energetic cost. PMID:26167931

  20. Rhythmic 24 h Variation of Core Body Temperature and Locomotor Activity in a Subterranean Rodent (Ctenomys aff. knighti), the Tuco-Tuco

    PubMed Central

    Tachinardi, Patricia; Bicudo, José Eduardo Wilken; Oda, Gisele Akemi; Valentinuzzi, Verónica Sandra

    2014-01-01

    The tuco-tuco Ctenomys aff. knighti is a subterranean rodent which inhabits a semi-arid area in Northwestern Argentina. Although they live in underground burrows where environmental cycles are attenuated, they display robust, 24 h locomotor activity rhythms that are synchronized by light/dark cycles, both in laboratory and field conditions. The underground environment also poses energetic challenges (e.g. high-energy demands of digging, hypoxia, high humidity, low food availability) that have motivated thermoregulation studies in several subterranean rodent species. By using chronobiological protocols, the present work aims to contribute towards these studies by exploring day-night variations of thermoregulatory functions in tuco-tucos, starting with body temperature and its temporal relationship to locomotor activity. Animals showed daily, 24 h body temperature rhythms that persisted even in constant darkness and temperature, synchronizing to a daily light/dark cycle, with highest values occurring during darkness hours. The range of oscillation of body temperature was slightly lower than those reported for similar-sized and dark-active rodents. Most rhythmic parameters, such as period and phase, did not change upon removal of the running wheel. Body temperature and locomotor activity rhythms were robustly associated in time. The former persisted even after removal of the acute effects of intense activity on body temperature by a statistical method. Finally, regression gradients between body temperature and activity were higher in the beginning of the night, suggesting day-night variation in thermal conductance and heat production. Consideration of these day-night variations in thermoregulatory processes is beneficial for further studies on thermoregulation and energetics of subterranean rodents. PMID:24454916

  1. Characterization of dopamine transporter and locomotor effects of cocaine, GBR 12909, epidepride, and SCH 23390 in C57BL and DBA mice.

    PubMed

    Womer, D E; Jones, B C; Erwin, V G

    1994-06-01

    C57BL/6 and DBA/2 mice were used to examine genetic differences in locomotor activating effects of acute cocaine administration and to determine whether differences were mediated by dopaminergic systems. C57BL/6 mice were less activated than DBA/2 mice at 5 and 10 min after 10 and 15 mg/kg cocaine. HPLC analysis showed equivalent brain cocaine concentrations in the two strains at 5 and 10 min after 10, 15, or 20 mg/kg doses. The selective dopamine uptake inhibitor, GBR 12909, at 5 and 7.5 mg/kg, produced greater locomotor activation in DBA/2 mice than in C57BL/6 mice. However, binding studies with the selective dopamine uptake ligand [3H]GBR 12935, revealed no between-strain difference in Kd or Bmax in caudate putamen (CP) or nucleus accumbens (NA) membranes. Competition assays using unlabeled dopamine to compete for [3H]GBR 12935 binding in CP or NA membranes showed no between-strain difference by brain region. The specific D1 or D2 antagonists, SCH 23390 or epidepride, respectively, produced dose-dependent decreases in locomotor activity but there were no between-strain differences. However, epidepride, at a dose of 0.003 mg/kg, completely reversed cocaine-induced (15 mg/kg) activation in both strains. These findings show that C57BL/6 and DBA/2 mice differ in dopamine-related behaviors and suggest that dopaminergic processes may mediate genetic differences in cocaine sensitivity. PMID:8090798

  2. Rhythmic 24 h variation of core body temperature and locomotor activity in a subterranean rodent (Ctenomys aff. knighti), the tuco-tuco.

    PubMed

    Tachinardi, Patricia; Bicudo, José Eduardo Wilken; Oda, Gisele Akemi; Valentinuzzi, Verónica Sandra

    2014-01-01

    The tuco-tuco Ctenomys aff. knighti is a subterranean rodent which inhabits a semi-arid area in Northwestern Argentina. Although they live in underground burrows where environmental cycles are attenuated, they display robust, 24 h locomotor activity rhythms that are synchronized by light/dark cycles, both in laboratory and field conditions. The underground environment also poses energetic challenges (e.g. high-energy demands of digging, hypoxia, high humidity, low food availability) that have motivated thermoregulation studies in several subterranean rodent species. By using chronobiological protocols, the present work aims to contribute towards these studies by exploring day-night variations of thermoregulatory functions in tuco-tucos, starting with body temperature and its temporal relationship to locomotor activity. Animals showed daily, 24 h body temperature rhythms that persisted even in constant darkness and temperature, synchronizing to a daily light/dark cycle, with highest values occurring during darkness hours. The range of oscillation of body temperature was slightly lower than those reported for similar-sized and dark-active rodents. Most rhythmic parameters, such as period and phase, did not change upon removal of the running wheel. Body temperature and locomotor activity rhythms were robustly associated in time. The former persisted even after removal of the acute effects of intense activity on body temperature by a statistical method. Finally, regression gradients between body temperature and activity were higher in the beginning of the night, suggesting day-night variation in thermal conductance and heat production. Consideration of these day-night variations in thermoregulatory processes is beneficial for further studies on thermoregulation and energetics of subterranean rodents. PMID:24454916

  3. Locomotor Dysfunction after Long-duration Space Flight and Development of Countermeasures to Facilitate Faster Recovery

    NASA Astrophysics Data System (ADS)

    Mulavara, Ajitkumar; Wood, Scott; Cohen, Helen; Bloomberg, Jacob

    2012-07-01

    movement control and a functional mobility test to investigate overall functional locomotor ability. Postflight sessions were given on days 1, 2, 4, 7 after their return. Subjects walked on a treadmill driven at 1.8 m/s while performing a visual task. Motion data from head and trunk segmental motion data were obtained to calculate the angular head pitch (HP) movements during walking trials while subjects performed the visual task, to estimate the contributions of vestibular reflexive mechanisms in HP movements. Astronauts showed a heterogeneous response pattern of both increases and decreases in the amplitude of HP movement. We investigated the underlying mechanisms of this heterogeneity in postflight responses in head movement control by examining data obtained using the same experimental test paradigm on a vestibular clinical population (VC) and in normal subjects undergoing adaptation to acute body load support unloading. Results showed that exposure to unloaded locomotion caused a significant increase in HP movements, whereas in the VC patients the HP movements were significantly decreased. We infer that BLS-mediated somatosensory input centrally modulates vestibular input and can adaptively modify head-movement control during locomotion. Thus, space flight may cause a central adaptation of the converging vestibular and body load-sensing somatosensory systems. To investigate changes in functional mobility astronaut subjects walked at their preferred pace around an obstacle course consisting of several pylons and obstacles set up on a foam floor, which provided an unstable walking surface. Subjects were instructed to walk around the course as fast as possible without touching any of the objects on the course for a total of six individual trials per test session. One of the dependent measures was time to complete the course (TCC, sec). The learning rate over the six trials performed on preflight and the first day after landing (micro curve) was used to characterize the

  4. Locomotor responses of human CD45 lymphocyte subsets: preferential locomotion of CD45RO+ lymphocytes in response to attractants and mitogens.

    PubMed Central

    Newman, I; Wilkinson, P C

    1993-01-01

    The CD45RO+ population of lymphocytes from human blood contains a higher proportion of locomotor cells than the CD45RA+ population. Direct from blood there were few locomotor lymphocytes (< 15%), but, among these, a higher proportion of CD45RO+ than of CD45RA+ cells responded to the chemotactic stimuli, foetal calf serum (FCS) and interleukin-2 (IL-2) in polarization assays. Likewise, after overnight culture, a higher proportion of CD45RO+ cells responded to IL-8. Culture for 24-72 hr in activators such as anti-CD3, purified protein derivative (PPD), phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) or in an allogeneic mixed leucocyte reaction (AMLR) increased the proportion of locomotor lymphocytes to 20-60%, and the CD45RO+ subset showed proportionately more polarized cells than the CD45RA+ subset after culture with all the above activators. Preferential migration of CD45RO+ cells into collagen gels was also seen after culture in antigenic stimuli (PPD or AMLR) but not with polyclonal activators (alpha CD3 or Con A). Double labelling showed that, within the CD4+ and CD8+ subsets, antigen-stimulated CD45RO+ T cells invaded collagen gels in higher proportions than CD45RA+ T cells. Clustering of lymphocytes with accessory cells is an essential prerequisite for locomotion and, after culture in alpha CD3, CD45RO+ lymphocytes were found preferentially in clusters with monocytes. In all of the above populations, CD45RO+ lymphocytes were larger in size. These findings suggest that, not only selective adhesion to vascular endothelium as reported earlier, but also selective locomotion recruits CD45RO+ lymphocytes into sites of inflammation. PMID:8436407

  5. Altered Patterns of Reflex Excitability, Balance, and Locomotion Following Spinal Cord Injury and Locomotor Training

    PubMed Central

    Bose, Prodip K.; Hou, Jiamei; Parmer, Ronald; Reier, Paul J.; Thompson, Floyd J.

    2012-01-01

    Spasticity is an important problem that complicates daily living in many individuals with spinal cord injury (SCI). While previous studies in human and animals revealed significant improvements in locomotor ability with treadmill locomotor training, it is not known to what extent locomotor training influences spasticity. In addition, it would be of considerable practical interest to know how the more ergonomically feasible cycle training compares with treadmill training as therapy to manage SCI-induced spasticity and to improve locomotor function. Thus the main objective of our present studies was to evaluate the influence of different types of locomotor training on measures of limb spasticity, gait, and reflex components that contribute to locomotion. For these studies, 30 animals received midthoracic SCI using the standard Multicenter Animal Spinal cord Injury Studies (MASCIS) protocol (10 g 2.5 cm weight drop). They were divided randomly into three equal groups: control (contused untrained), contused treadmill trained, and contused cycle trained. Treadmill and cycle training were started on post-injury day 8. Velocity-dependent ankle torque was tested across a wide range of velocities (612–49°/s) to permit quantitation of tonic (low velocity) and dynamic (high velocity) contributions to lower limb spasticity. By post-injury weeks 4 and 6, the untrained group revealed significant velocity-dependent ankle extensor spasticity, compared to pre-surgical control values. At these post-injury time points, spasticity was not observed in either of the two training groups. Instead, a significantly milder form of velocity-dependent spasticity was detected at postcontusion weeks 8–12 in both treadmill and bicycle training groups at the four fastest ankle rotation velocities (350–612°/s). Locomotor training using treadmill or bicycle also produced significant increase in the rate of recovery of limb placement measures (limb axis, base of support, and open field

  6. Interplay between postcranial morphology and locomotor types in Neotropical sigmodontine rodents

    PubMed Central

    Carrizo, Luz V; Tulli, María J; Dos Santos, Daniel A; Abdala, Virginia

    2014-01-01

    Sigmodontine rats are one of the most diverse components of the Neotropical mammal fauna. They exhibit a wide ecological diversity and a variety of locomotor types that allow them to occupy different environments. To explore the relationship between morphology and locomotor types, we analyzed traits of the postcranial osteology (axial and appendicular skeletons) of 329 specimens belonging to 51 species and 29 genera of sigmodontines exhibiting different locomotor types. In this work, postcranial skeletal characters of these rats are considered in an ecomorphological study for the first time. Statistical analyses showed that of the 34 osteological characters considered, 15 were related to the locomotor types studied, except for ambulatory. However, character mapping showed that climbing and jumping sigmodontines are the only taxa exhibiting clear adaptations in their postcranial osteology, which are highly consistent with the tendencies described in many other mammal taxa. Climbing, digging and swimming rats presented statistically differences in traits associated with their vertebral column and limbs, whereas jumping rats showed modifications associated with all the skeletal regions. Our data suggest that sigmodontine rats retain an all-purpose morphology that allows them to use a variety of habitats. This versatility is particularly important when considering the lack of specialization of sigmodontines for a specific locomotor mode. Another possible interpretation is that our dataset probably did not consider relevant information about these groups and should be increased with other types of characters (e.g. characters from the external morphology, myology, etc.). PMID:24372154

  7. A feasibility study on the design and walking operation of a biped locomotor via dynamic simulation

    NASA Astrophysics Data System (ADS)

    Wang, Mingfeng; Ceccarelli, Marco; Carbone, Giuseppe

    2016-06-01

    A feasibility study on the mechanical design and walking operation of a Cassino biped locomotor is presented in this paper. The biped locomotor consists of two identical 3 degrees-of-freedom tripod leg mechanisms with a parallel manipulator architecture. Planning of the biped walking gait is performed by coordinating the motions of the two leg mechanisms and waist. A threedimensional model is elaborated in SolidWorks® environment in order to characterize a feasible mechanical design. Dynamic simulation is carried out in MSC.ADAMS® environment with the aims of characterizing and evaluating the dynamic walking performance of the proposed design. Simulation results show that the proposed biped locomotor with proper input motions of linear actuators performs practical and feasible walking on flat surfaces with limited actuation and reaction forces between its feet and the ground. A preliminary prototype of the biped locomotor is built for the purpose of evaluating the operation performance of the biped walking gait of the proposed locomotor.

  8. Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression.

    PubMed

    Tortorelli, Lucas Silva; Engelke, Douglas Senna; Lunardi, Paula; Mello E Souza, Tadeu; Santos-Junior, Jair Guilherme; Gonçalves, Carlos-Alberto

    2015-01-01

    Neuroimmune signalling underlies addiction and comorbid depression. Clinical observations indicate that infections and chronic lesions are more frequent in drug users and elevated inflammatory states are evident in cocaine dependents. Therefore, lipopolysaccharide (LPS) and inflammatory cytokines represent an important tool for the investigation of sickness, depressive illness and addiction behaviour. A major component of addiction is the progressive and persistent increase in locomotor activity after repeated drug administration and even prolonged periods of abstinence. The aim of this study was to investigate the response of locomotor sensitization when a non-sensitizing dose of cocaine is paired with a systemic inflammatory stimulus. LPS and cocaine were administered intraperitonealy in young-adult male C57bl/6 mice during a 5-day acquisition phase. After a 48-h withdrawal period all groups were challenged with cocaine to evaluate locomotor expression. During the acquisition phase, the LPS-treated groups displayed characteristic hypolocomotion related to sickness behaviour. The low dose of cocaine did not increase the distance travelled, characterizing a non-sensitization dose. Groups that received both LPS and cocaine did not display hypolocomotion, indicating that cocaine might counteract hypolocomotion sickness behaviour. Moreover, during challenge, only these animals expressed locomotor sensitization. Our results indicate that LPS could facilitate the expression of locomotor sensitization in mice and that the immune system may modulate cocaine-induced sensitization. PMID:25835320

  9. Repeated stimulation of dopamine D1-like receptor and hyperactivation of mTOR signaling lead to generalized seizures, altered dentate gyrus plasticity, and memory deficits.

    PubMed

    Gangarossa, Giuseppe; Ceolin, Laura; Paucard, Alexia; Lerner-Natoli, Mireille; Perroy, Julie; Fagni, Laurent; Valjent, Emmanuel

    2014-12-01

    The acute activation of the dopamine D1-like receptors (D1R) is involved in a plethora of functions ranging from increased locomotor activity to the facilitation of consolidation, storage, and retrieval of memories. Although much less characterized, epileptiform activities, usually triggered by disruption of the glutamate and GABA balance, have also been reported to involve the dopaminergic transmission. Using a combination of biochemical, immunohistochemical, electrophysiological, and behavioral approaches we have investigated the consequences of repeated stimulation of D1R using the selective D1R-like agonist SKF81297. Here, we report that repeated systemic administration of SKF81297 induces kindled seizures in mice. These seizure episodes parallel the hyperactivation of the mTOR signaling in the hippocampus, leading to disrupted long-term potentiation (LTP) in the dentate gyrus (DG) and altered recognition memories. The mTOR inhibitor rapamycin delays the development of SKF81297-induced kindled seizures, and rescues LTP in the DG and object recognition. Our results show that repeated stimulation of D1R is sufficient to induce generalized seizures leading to the overactivation of mTOR signaling, disrupted hippocampal plasticity, and impaired long-term recognition memories. This work highlights the interest of mTOR inhibitors as therapeutic strategies to reverse plasticity and cognitive deficits. PMID:25044816

  10. Frequency dependence of behavioral modulation by hippocampal electrical stimulation

    PubMed Central

    La Corte, Giorgio; Wei, Yina; Chernyy, Nick; Gluckman, Bruce J.

    2013-01-01

    Electrical stimulation offers the potential to develop novel strategies for the treatment of refractory medial temporal lobe epilepsy. In particular, direct electrical stimulation of the hippocampus presents the opportunity to modulate pathological dynamics at the ictal focus, although the neuroanatomical substrate of this region renders it susceptible to altering cognition and affective processing as a side effect. We investigated the effects of three electrical stimulation paradigms on separate groups of freely moving rats (sham, 8-Hz and 40-Hz sine-wave stimulation of the ventral/intermediate hippocampus, where 8- and 40-Hz stimulation were chosen to mimic naturally occurring hippocampal oscillations). Animals exhibited attenuated locomotor and exploratory activity upon stimulation at 40 Hz, but not at sham or 8-Hz stimulation. Such behavioral modifications were characterized by a significant reduction in rearing frequency, together with increased freezing behavior. Logistic regression analysis linked the observed changes in animal locomotion to 40-Hz electrical stimulation independently of time-related variables occurring during testing. Spectral analysis, conducted to monitor the electrophysiological profile in the CA1 area of the dorsal hippocampus, showed a significant reduction in peak theta frequency, together with reduced theta power in the 40-Hz vs. the sham stimulation animal group, independent of locomotion speed (theta range: 4–12 Hz). These findings contribute to the development of novel and safe medical protocols by indicating a strategy to constrain or optimize parameters in direct hippocampal electrical stimulation. PMID:24198322

  11. Fenproporex increases locomotor activity and alters energy metabolism, and mood stabilizers reverse these changes: a proposal for a new animal model of mania.

    PubMed

    Rezin, Gislaine T; Furlanetto, Camila B; Scaini, Giselli; Valvassori, Samira S; Gonçalves, Cinara L; Ferreira, Gabriela K; Jeremias, Isabela C; Resende, Wilson R; Cardoso, Mariane R; Varela, Roger B; Quevedo, João; Streck, Emilio L

    2014-04-01

    Fenproporex (Fen) is converted in vivo into amphetamine, which is used to induce mania-like behaviors in animals. In the present study, we intend to present a new animal model of mania. In order to prove through face, construct, and predictive validities, we evaluated behavioral parameters (locomotor activity, stereotypy activity, and fecal boli amount) and brain energy metabolism (enzymes citrate synthase; malate dehydrogenase; succinate dehydrogenase; complexes I, II, II-III, and IV of the mitochondrial respiratory chain; and creatine kinase) in rats submitted to acute and chronic administration of fenproporex, treated with lithium (Li) and valproate (VPA). The administration of Fen increased locomotor activity and decreased the activity of Krebs cycle enzymes, mitochondrial respiratory chain complexes, and creatine kinase, in most brain structures evaluated. In addition, treatment with mood stabilizers prevented and reversed this effect. Our results are consistent with the literature that demonstrates behavioral changes and mitochondrial dysfunction caused by psychostimulants. These findings suggest that chronic administration of Fen may be a potential animal model of mania. PMID:24126971

  12. Rats classified as low or high cocaine locomotor responders: A unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors

    PubMed Central

    Yamamoto, Dorothy J.; Nelson, Anna M.; Mandt, Bruce H.; Larson, Gaynor A.; Rorabaugh, Jacki M.; Ng, Christopher M.C.; Barcomb, Kelsey M.; Richards, Toni L.; Allen, Richard M.; Zahniser, Nancy R.

    2013-01-01

    Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition of in vivo DAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine’s discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors. PMID:23850581

  13. Rats classified as low or high cocaine locomotor responders: a unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors.

    PubMed

    Yamamoto, Dorothy J; Nelson, Anna M; Mandt, Bruce H; Larson, Gaynor A; Rorabaugh, Jacki M; Ng, Christopher M C; Barcomb, Kelsey M; Richards, Toni L; Allen, Richard M; Zahniser, Nancy R

    2013-09-01

    Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition of in vivo DAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine's discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors. PMID:23850581

  14. [Detection of nootropic activity indicated by acute inhibition of orientation reaction].

    PubMed

    Ostrovskaia, R U; Gudasheva, T A

    1991-05-01

    Exploratory locomotor activity was studied in the experiments on adult male mice. It was shown that routine nootropic drugs as well as newly synthesized nootropic compounds were able to facilitate the development of inhibition during one registration session. Inhibition may be used for revealing only selective nootropic drugs devoid of sedative and stimulating effects. PMID:1878564

  15. Do morphological condition indices predict locomotor performance in the lizard Podarcis sicula?

    NASA Astrophysics Data System (ADS)

    Vervust, Bart; Lailvaux, Simon P.; Grbac, Irena; Van Damme, Raoul

    2008-09-01

    Biologists have developed a number of simple metrics to assess the health and energetic status of individual organisms and populations. While these condition indices have been widely used to address questions in evolutionary ecology and conservation biology, the ability of such indices to predict ecologically relevant locomotor performance abilities remains unknown. We show here that the functional links between six commonly used morphological condition indices and locomotor performance in two populations of Adriatic lizards ( Podarcis sicula) are weak at best. Indeed, no indices consistently predict either maximum sprint speed or maximum exertion across sexes, seasons or populations. These results cast doubt on the ecological relevance of morphological condition indices in terms of locomotor performance, measured in laboratory conditions, at least in this species. We urge caution in using condition indices as proxies for individual physiological or phenotypic quality in ecological and evolutionary studies.

  16. Voluntary locomotor activity mitigates oxidative damage associated with isolation stress in the prairie vole (Microtus ochrogaster)

    PubMed Central

    Fletcher, Kelsey L.; Whitley, Brittany N.; Treidel, Lisa A.; Thompson, David; Williams, Annie; Noguera, Jose C.; Stevenson, Jennie R.; Haussmann, Mark F.

    2015-01-01

    Organismal performance directly depends on an individual's ability to cope with a wide array of physiological challenges. For social animals, social isolation is a stressor that has been shown to increase oxidative stress. Another physiological challenge, routine locomotor activity, has been found to decrease oxidative stress levels. Because we currently do not have a good understanding of how diverse physiological systems like stress and locomotion interact to affect oxidative balance, we studied this interaction in the prairie vole (Microtus ochrogaster). Voles were either pair housed or isolated and within the isolation group, voles either had access to a moving wheel or a stationary wheel. We found that chronic periodic isolation caused increased levels of oxidative stress. However, within the vole group that was able to run voluntarily, longer durations of locomotor activity were associated with less oxidative stress. Our work suggests that individuals who demonstrate increased locomotor activity may be better able to cope with the social stressor of isolation. PMID:26179798

  17. Voluntary locomotor activity mitigates oxidative damage associated with isolation stress in the prairie vole (Microtus ochrogaster).

    PubMed

    Fletcher, Kelsey L; Whitley, Brittany N; Treidel, Lisa A; Thompson, David; Williams, Annie; Noguera, Jose C; Stevenson, Jennie R; Haussmann, Mark F

    2015-07-01

    Organismal performance directly depends on an individual's ability to cope with a wide array of physiological challenges. For social animals, social isolation is a stressor that has been shown to increase oxidative stress. Another physiological challenge, routine locomotor activity, has been found to decrease oxidative stress levels. Because we currently do not have a good understanding of how diverse physiological systems like stress and locomotion interact to affect oxidative balance, we studied this interaction in the prairie vole (Microtus ochrogaster). Voles were either pair housed or isolated and within the isolation group, voles either had access to a moving wheel or a stationary wheel. We found that chronic periodic isolation caused increased levels of oxidative stress. However, within the vole group that was able to run voluntarily, longer durations of locomotor activity were associated with less oxidative stress. Our work suggests that individuals who demonstrate increased locomotor activity may be better able to cope with the social stressor of isolation. PMID:26179798

  18. Plasticity and modular control of locomotor patterns in neurological disorders with motor deficits

    PubMed Central

    Ivanenko, Y. P.; Cappellini, G.; Solopova, I. A.; Grishin, A. A.; MacLellan, M. J.; Poppele, R. E.; Lacquaniti, F.

    2013-01-01

    Human locomotor movements exhibit considerable variability and are highly complex in terms of both neural activation and biomechanical output. The building blocks with which the central nervous system constructs these motor patterns can be preserved in patients with various sensory-motor disorders. In particular, several studies highlighted a modular burst-like organization of the muscle activity. Here we review and discuss this issue with a particular emphasis on the various examples of adaptation of locomotor patterns in patients (with large fiber neuropathy, amputees, stroke and spinal cord injury). The results highlight plasticity and different solutions to reorganize muscle patterns in both peripheral and central nervous system lesions. The findings are discussed in a general context of compensatory gait mechanisms, spatiotemporal architecture and modularity of the locomotor program. PMID:24032016

  19. Differential Effects of Sex Pheromone Compounds on Adult Female Sea Lamprey (Petromyzon marinus) Locomotor Patterns.

    PubMed

    Walaszczyk, Erin J; Goheen, Benjamin B; Steibel, Juan Pedro; Li, Weiming

    2016-06-01

    Synchronization of male and female locomotor activity plays a critical role in ensuring reproductive success, especially in semelparous species. The goal of this study was to elucidate the effects of individual chemical signals, or pheromones, on the locomotor activity in the sea lamprey (Petromyzon marinus). In their native habitat, adult preovulated females (POF) and ovulated females (OF) are exposed to sex pheromone compounds that are released from spermiated males and attract females to nests during their migration and spawning periods. In this study, locomotor activity of individual POF and OF was measured hourly in controlled laboratory conditions using an automated video-tracking system. Differences in the activity between a baseline day (no treatment exposure) and a treatment day (sex pheromone compound or control exposure) were examined for daytime and nighttime periods. Results showed that different pheromone compound treatments affected both POF and OF sea lamprey (p < 0.05) but in different ways. Spermiated male washings (SMW) and one of its main components, 7α,12α,24-trihydroxy-5α-cholan-3-one 24 sulfate (3kPZS), decreased activity of POF during the nighttime. SMW also reduced activity in POF during the daytime. In contrast, SMW increased activity of OF during the daytime, and an additional compound found in SMW, petromyzonol sulfate (PZS), decreased the activity during the nighttime. In addition, we examined factors that allowed us to infer the overall locomotor patterns. SMW increased the maximum hourly activity during the daytime, decreased the maximum hourly activity during the nighttime, and reduced the percentage of nocturnal activity in OF. Our findings suggest that adult females have evolved to respond to different male compounds in regards to their locomotor activity before and after final maturation. This is a rare example of how species-wide chemosensory stimuli can affect not only the amounts of activity but also the overall locomotor

  20. Kinematic study of locomotor recovery after spinal cord clip compression injury in rats.

    PubMed

    Alluin, Olivier; Karimi-Abdolrezaee, Soheila; Delivet-Mongrain, Hugo; Leblond, Hugues; Fehlings, Michael G; Rossignol, Serge

    2011-09-01

    After spinal cord injury (SCI), precise assessment of motor recovery is essential to evaluate the outcome of new therapeutic approaches. Very little is known on the recovery of kinematic parameters after clinically-relevant severe compressive/contusive incomplete spinal cord lesions in experimental animal models. In the present study we evaluated the time-course of kinematic parameters during a 6-week period in rats walking on a treadmill after a severe thoracic clip compression SCI. The effect of daily treadmill training was also assessed. During the recovery period, a significant amount of spontaneous locomotor recovery occurred in 80% of the rats with a return of well-defined locomotor hindlimb pattern, regular plantar stepping, toe clearance and homologous hindlimb coupling. However, substantial residual abnormalities persisted up to 6 weeks after SCI including postural deficits, a bias of the hindlimb locomotor cycle toward the back of the animals with overextension at the swing/stance transition, loss of lateral balance and impairment of weight bearing. Although rats never recovered the antero-posterior (i.e. homolateral) coupling, different levels of decoupling between the fore and hindlimbs were measured. We also showed that treadmill training increased the swing duration variability during locomotion suggesting an activity-dependent compensatory mechanism of the motor control system. However, no effect of training was observed on the main locomotor parameters probably due to a ceiling effect of self-training in the cage. These findings constitute a kinematic baseline of locomotor recovery after clinically relevant SCI in rats and should be taken into account when evaluating various therapeutic strategies aimed at improving locomotor function. PMID:21770755

  1. Acute Bronchitis

    MedlinePlus

    ... or though physical contact (for example, on unwashed hands). Being exposed to tobacco smoke, air pollution, dusts, vapors, and fumes can also cause acute bronchitis. Less often, bacteria can also cause acute bronchitis. To diagnose acute ...

  2. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  3. A fully implanted programmable stimulator based on wireless communication for epidural spinal cord stimulation in rats.

    PubMed

    Zhou, Hui; Xu, Qi; He, Jiping; Ren, Hangkong; Zhou, Houlun; Zheng, Kejia

    2012-03-15

    Clinical research indicates that the epidural spinal cord stimulation (ESCS) has shown potential in promoting locomotor recovery in patients with incomplete spinal cord injury (ISCI). This paper presents the development of a fully implantable voltage-regulated stimulator with bi-directional wireless communication for investigating underlying neural mechanisms of ESCS facilitating motor function improvement. The stimulation system consists of a computer, an external controller, an implantable pulse generator (IPG), a magnet, the extension leads and a stimulation electrode. The telemetry transmission between the IPG and the external controller is achieved by a commercially available transceiver chip with 2.4GHz carrier band. The magnet is used to activate the IPG only when necessary to minimize the power consumption. The encapsulated IPG measures 33mm×24mm×8mm, with a total mass of ∼12.6g. Feasibility experiments are conducted in three Sprague-Dawley rats to validate the function of the stimulator, and to investigate the relationship between lumbar-sacral ESCS and hindlimb electromyography (EMG) responses. The results show that the stimulation system provides an effective tool for investigation of ESCS application in motor function recovery in small animals. PMID:22085835

  4. The locomotor system as seen in Brazilian scientific journals: a mini review

    PubMed Central

    Rocha e Silva, Mauricio

    2010-01-01

    OBJECTIVE: To make recent selected publications on the locomotor system available to the readership of Clinics. METHOD: A general survey of articles published in selected Brazilian journals was inspected and 91 articles were critically analyzed. They were categorized and briefly described. A final summary of themes is reproduced here. RESULTS: Papers fall into two main categories: articular and muscular pathology and therapeutics; medical sports. A number of papers are not classifiable under these headings. CONCLUSION: The locomotor system has been extensively analyzed and discussed in the Brazilian scientific press in recent years. Not surprisingly, knee and ankle pathology, soccer and running are dominant themes. PMID:21340230

  5. A novel approach in automatic estimation of rats' loco-motor activity

    NASA Astrophysics Data System (ADS)

    Anishchenko, Lesya N.; Ivashov, Sergey I.; Vasiliev, Igor A.

    2014-05-01

    The paper contains feasibility study of a method for bioradar monitoring of small laboratory animals loco-motor activity improved by using a corner reflector. It presents results of mathematical simulation of bioradar signal reflection from the animal with the help of finite-difference time-domain method. It was proved both by theoretical and experimental results that a corner reflector usage during monitoring of small laboratory animals loco-motor activity improved the effectiveness of the method by reducing the dependency of the power flux density level from the distance between antennas block and the object.

  6. Encounters with aggressive conspecifics enhance the locomotor-activating effects of cocaine in the rat.

    PubMed

    Marrow, L P; Overton, P G; Brain, P F; Clark, D

    1999-10-01

    Evidence suggests that stress enhances the behavioural actions of cocaine in the rat. Paradoxically, however, encounters with aggressive conspecifics lead to a pattern of cocaine self-administration indicative of a reduced functional impact of the drug. Hence, we examined the effects of aggressive encounters on another behavioural measure-locomotor activity. Encounters between Lister Hooded rats and rats of the aggressive Tryon Maze Dull strain significantly enhanced the locomotor-activating effects of cocaine (20 mg/kg) in the Lister Hooded rats. The results suggest that the discrepant findings derived from self-administration studies are a property of the paradigm rather than a property of the stressor. PMID:20575812

  7. Ventral Tegmental Area Neurotensin Signaling Links the Lateral Hypothalamus to Locomotor Activity and Striatal Dopamine Efflux in Male Mice

    PubMed Central

    Patterson, Christa M.; Wong, Jenny-Marie T.; Leinninger, Gina M.; Allison, Margaret B.; Mabrouk, Omar S.; Kasper, Chelsea L.; Gonzalez, Ian E.; Mackenzie, Alexander; Jones, Justin C.

    2015-01-01

    Projections from the lateral hypothalamic area (LHA) innervate components of the mesolimbic dopamine (MLDA) system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc), to modulate motivation appropriately for physiologic state. Neurotensin (NT)-containing LHA neurons respond to multiple homeostatic challenges and project to the VTA, suggesting that these neurons could link such signals to MLDA function. Indeed, we found that pharmacogenetic activation of LHA NT neurons promoted prolonged DA-dependent locomotor activity and NAc DA efflux, suggesting the importance of VTA neurotransmitter release by LHA NT neurons for the control of MLDA function. Using a microdialysis-mass spectrometry technique that we developed to detect endogenous NT in extracellular fluid in the mouse brain, we found that activation of LHA NT cells acutely increased the extracellular concentration of NT (a known activator of VTA DA cells) in the VTA. In contrast to the prolonged elevation of extracellular NAc DA, however, VTA NT concentrations rapidly returned to baseline. Intra-VTA infusion of NT receptor antagonist abrogated the ability of LHA NT cells to increase extracellular DA in the NAc, demonstrating that VTA NT promotes NAc DA release. Thus, transient LHA-derived NT release in the VTA couples LHA signaling to prolonged changes in DA efflux and MLDA function. PMID:25734363

  8. Transplanted oligodendrocytes and motoneuron progenitors generated from human embryonic stem cells promote locomotor recovery after spinal cord transection.

    PubMed

    Erceg, Slaven; Ronaghi, Mohammad; Oria, Marc; Roselló, Mireia García; Aragó, Maria Amparo Pérez; Lopez, Maria Gomez; Radojevic, Ivana; Moreno-Manzano, Victoria; Rodríguez-Jiménez, Francisco-Javier; Bhattacharya, Shom Shanker; Cordoba, Juan; Stojkovic, Miodrag

    2010-09-01

    Human embryonic stem cells (hESC) hold great promise for the treatment of patients with many neurodegenerative diseases particularly those arising from cell loss or neural dysfunction including spinal cord injury. This study evaluates the therapeutic effects of transplanted hESC-derived oligodendrocyte progenitors (OPC) and/or motoneuron progenitors (MP) on axonal remyelination and functional recovery of adult rats after complete spinal cord transection. OPC and/or MP were grafted into the site of injury in the acute phase. Based on Basso-Beattie-Bresnahan scores recovery of locomotor function was significantly enhanced in rats treated with OPC and/or MP when compared with control animals. When transplanted into the spinal cord immediately after complete transection, OPC and MP survived, migrated, and differentiated into mature oligodendrocytes and neurons showing in vivo electrophysiological activity. Taken together, these results indicate that OPC and MP derived from hESC could be a useful therapeutic strategy to repair injured spinal cord. PMID:20665739

  9. Transplanted Oligodendrocytes and Motoneuron Progenitors Generated from Human Embryonic Stem Cells Promote Locomotor Recovery After Spinal Cord Transection

    PubMed Central

    Erceg, Slaven; Ronaghi, Mohammad; Oria, Marc; García Roselló, Mireia; Aragó, Maria Amparo Pérez; Lopez, Maria Gomez; Radojevic, Ivana; Moreno-Manzano, Victoria; Rodríguez-Jiménez, Francisco-Javier; Shanker Bhattacharya, Shom; Cordoba, Juan; Stojkovic, Miodrag

    2010-01-01

    Human embryonic stem cells (hESC) hold great promise for the treatment of patients with many neurodegenerative diseases particularly those arising from cell loss or neural dysfunction including spinal cord injury. This study evaluates the therapeutic effects of transplanted hESC-derived oligodendrocyte progenitors (OPC) and/or motoneuron progenitors (MP) on axonal remyelination and functional recovery of adult rats after complete spinal cord transection. OPC and/or MP were grafted into the site of injury in the acute phase. Based on Basso-Beattie-Bresnahan scores recovery of locomotor function was significantly enhanced in rats treated with OPC and/or MP when compared with control animals. When transplanted into the spinal cord immediately after complete transection, OPC and MP survived, migrated, and differentiated into mature oligodendrocytes and neurons showing in vivo electrophysiological activity. Taken together, these results indicate that OPC and MP derived from hESC could be a useful therapeutic strategy to repair injured spinal cord. Stem Cells 2010; 28:1541–1549. PMID:20665739

  10. AMPHETAMINE-, SCOPOLAMINE-, AND CAFFEINE-INDUCED LOCOMOTOR ACTIVITY FOLLOWING 6-HYDROXYDOPAMINE LESIONS OF THE MESOLIMBIC DOPAMINE SYSTEM

    EPA Science Inventory

    As previously reported, 6-hydroxydopamine (6-OHDA) lesions to the region of the nucleus accumbens blocked the locomotor activation induced by low doses of d-amphetamine, and produced a supersensitive locomotor response to the dopamine (DA) agonist, apomorphine. This same lesion, ...

  11. Quantification of locomotor activity in larval zebrafish: considerations for the design of high-throughput behavioral studies

    PubMed Central

    Ingebretson, Justin J.; Masino, Mark A.

    2013-01-01

    High-throughput behavioral studies using larval zebrafish often assess locomotor activity to determine the effects of experimental perturbations. However, the results reported by different groups are difficult to compare because there is not a standardized experimental paradigm or measure of locomotor activity. To address this, we investigated the effects that several factors, including the stage of larval development and the physical dimensions (depth and diameter) of the behavioral arena, have on the locomotor activity produced by larval zebrafish. We provide evidence for differences in locomotor activity between larvae at different stages and when recorded in wells of different depths, but not in wells of different diameters. We also show that the variability for most properties of locomotor activity is less for older than younger larvae, which is consistent with previous reports. Finally, we show that conflicting interpretations of activity level can occur when activity is assessed with a single measure of locomotor activity. Thus, we conclude that although a combination of factors should be considered when designing behavioral experiments, the use of older larvae in deep wells will reduce the variability of locomotor activity, and that multiple properties of locomotor activity should be measured to determine activity level. PMID:23772207

  12. Infant Stimulation.

    ERIC Educational Resources Information Center

    International Children's Centre, Paris (France).

    This set of documents consists of English, French, and Spanish translations of four pamphlets on infant stimulation. The pamphlets provide information designed for lay persons, educators and primary care personnel, academics and professionals, and for health administrators and family-planning organizations. The contents cover infant needs; infant…

  13. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    PubMed Central

    Amin, Bahareh; Nakhsaz, Alireza; Hosseinzadeh, Hossein

    2015-01-01

    Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration. PMID:26468466

  14. Pharmacological Effects of a Monoclonal Antibody against 6-Monoacetylmorphine upon Heroin-Induced Locomotor Activity and Pharmacokinetics in Mice.

    PubMed

    Kvello, Anne Marte Sjursen; Andersen, Jannike Mørch; Øiestad, Elisabeth Leere; Mørland, Jørg; Bogen, Inger Lise

    2016-08-01

    Immunotherapy can provide a supplemental treatment strategy against heroin use on the principle of sequestering the active drug in the bloodstream, thereby reducing its distribution to the brain. Previous studies have shown that heroin's first metabolite, 6-monoacetylmorphine (6-MAM), is the main mediator of acute heroin effects. The objective of the present study was to characterize the pharmacological potential of a monoclonal antibody against 6-MAM (anti-6-MAM mAb) to counteract the heroin response. The individual contributions from heroin and 6-MAM to heroin effects were also examined by pretreating mice with anti-6-MAM mAb (10-100 mg/kg) prior to either heroin or 6-MAM injection (1.25-2.5 μmol/kg). The opioid-induced behavioral response was assessed in a locomotor activity test, followed by opioid and antibody quantification in blood and brain tissue. Pretreatment with mAb caused a profound reduction of heroin- and 6-MAM-induced behavior, accompanied by correspondingly decreased levels of 6-MAM in brain tissue. mAb pretreatment was more efficient against 6-MAM injection than against heroin, leading to an almost complete blockade of 6-MAM-induced effects. mAb pretreatment was unable to block the immediate (5-minute) transport of active metabolites across the blood-brain barrier after heroin injection, indicating that heroin itself appears to enhance the immediate delivery of 6-MAM to the brain. The current study provides additional evidence that 6-MAM sequestration is crucial for counteracting the acute heroin response, and demonstrates the pharmacological potential of immunotherapy against heroin use. PMID:27217591

  15. Effects of acute feed restriction combined with targeted use of increasing luteinizing hormone content of follicle-stimulating hormone preparations on ovarian superstimulation, fertilization, and embryo quality in lactating dairy cows.

    PubMed

    Bender, R W; Hackbart, K S; Dresch, A R; Carvalho, P D; Vieira, L M; Crump, P M; Guenther, J N; Fricke, P M; Shaver, R D; Combs, D K; Wiltbank, M C

    2014-02-01

    Multiple metabolic and hormonal factors can affect the success of protocols for ovarian superstimulation. In this study, the effect of acute feed restriction and increased LH content in the superstimulatory FSH preparation on numbers of ovulations, fertilization, and embryo quality in lactating dairy cows was evaluated. Two experiments were performed using a Latin square design with treatments arranged as a 2 × 2 factorial: feed restriction (FR; 25% reduction in dry matter intake) compared with ad libitum (AL) feeding, combined with high (H) versus low (L) LH in the last 4 injections of the superstimulatory protocol. As expected, FR decreased circulating insulin concentrations (26.7 vs. 46.0 μU/mL). Two analyses were performed: one that evaluated the complete Latin square in experiment 2 and a second that evaluated only the first periods of experiments 1 and 2. For both analyses, follicle numbers, ovulation rates, and corpora lutea on d 7 were not different. In the first period analysis of experiments 1 and 2, we observed an interaction between feed allowance and amount of LH on fertilization rates, percentage of embryos or oocytes that were quality 1 and 2 embryos, and number of embryos or oocytes that were degenerate. Fertilization rates were greater for the AL-L (89.4%) and FR-H (80.1%) treatments compared with the AL-H (47.9%) and FR-L (59.9%) treatments. Similarly, the proportion of total embryos or oocytes designated as quality 1 and 2 embryos was greater for AL-L (76.7%) and FR-H (73.4%) treatments compared with AL-H (35.6%) and FR-L (47.3%) treatments. In addition, the number of degenerate embryos was decreased for AL-L (1.3) and FR-H (0.4) treatments compared with the AL-H (2.6) and FR-L (2.3) treatments. Thus, cows with either too low (FR-L) or too high (AL-H) insulin and LH stimulation had lesser embryo production after superstimulation because of reduced fertilization rate and increased percentage of degenerate embryos. Therefore, interaction of the

  16. The Developmental Effect of Concurrent Cognitive and Locomotor Skills: Time-Sharing from a Dynamical Perspective.

    ERIC Educational Resources Information Center

    Whitall, Jill

    1991-01-01

    Presents research on the effects of concurrent verbal cognition on locomotor skills. Results revealed no interference with coordination variables across age, but some interference with control variables, particularly in younger subjects. Coordination of gait required less attention than setting of control parameters. This coordination was in place…

  17. Prenatal Iron Deficiency in Guinea Pigs Increases Locomotor Activity but Does Not Influence Learning and Memory

    PubMed Central

    Fiset, Catherine; Rioux, France M.; Surette, Marc E.; Fiset, Sylvain

    2015-01-01

    The objective of the current study was to determine whether prenatal iron deficiency induced during gestation in guinea pigs affected locomotor activity and learning and memory processes in the progeny. Dams were fed either iron-deficient anemic or iron-sufficient diets throughout gestation and lactation. After weaning, all pups were fed an iron-sufficient diet. On postnatal day 24 and 40, the pups’ locomotor activity was observed within an open-field test, and from postnatal day 25 to 40, their learning and memory processes were assessed within a Morris Water Maze. The behavioural and cognitive tests revealed that the iron deficient pup group had increased locomotor activity, but solely on postnatal day 40, and that there were no group differences in the Morris Water Maze. In the general discussion, we propose that prenatal iron deficiency induces an increase in nervousness due to anxiety in the progeny, which, in the current study, resulted in an increase of locomotor activity. PMID:26186713

  18. Chemogenetic ablation of dopaminergic neurons leads to transient locomotor impairments in zebrafish larvae.

    PubMed

    Godoy, Rafael; Noble, Sandra; Yoon, Kevin; Anisman, Hymie; Ekker, Marc

    2015-10-01

    To determine the impact of a controlled loss of dopaminergic neurons on locomotor function, we generated transgenic zebrafish, Tg(dat:CFP-NTR), expressing a cyan fluorescent protein-nitroreductase fusion protein (CFP-NTR) under the control of dopamine transporter (dat) cis-regulatory elements. Embryonic and larval zebrafish express the transgene in several groups of dopaminergic neurons, notably in the olfactory bulb, telencephalon, diencephalon and caudal hypothalamus. Administration of the pro-drug metronidazole (Mtz) resulted in activation of caspase 3 in CFP-positive neurons and in a reduction in dat-positive cells by 5 days post-fertilization (dpf). Loss of neurons coincided with impairments in global locomotor parameters such as swimming distance, percentage of time spent moving, as well as changes in tail bend parameters such as time to maximal bend and angular velocity. Dopamine levels were transiently decreased following Mtz administration. Recovery of some of the locomotor parameters was observed by 7 dpf. However, the total numbers of dat-expressing neurons were still decreased at 7, 12, or 14 dpf, even though there was evidence for production of new dat-expressing cells. Tg(dat:CFP-NTR) zebrafish provide a model to correlate altered dopaminergic neuron numbers with locomotor function and to investigate factors influencing regeneration of dopaminergic neurons. PMID:26118896

  19. An automated tracking system for Caenorhabditis elegans locomotor behavior and circadian studies application.

    PubMed

    Simonetta, Sergio H; Golombek, Diego A

    2007-04-15

    Automation of simple behavioral patterns, such as locomotor activity, is fundamental for pharmacological and genetic screening studies. Recently, circadian behaviors in locomotor activity and stress responses were reported in the nematode Caenorhabditis elegans, a well-known model in genetics and developmental studies. Here we present a new method for long-term recordings of C. elegans (as well as other similar-sized animals) locomotor activity based on an infrared microbeam scattering. Individual nematodes were cultured in a 96-well microtiter plate; we tested L15, CeMM and E. coli liquid cultures in long-term activity tracking experiments, and found CeMM to be the optimal medium. Treatment with 0.2% azide caused an immediate decrease in locomotor activity as recorded with our system. In addition to the validation of the method (including hardware and software details), we report its application in chronobiological studies. Circadian rhythms in animals entrained to light-dark and constant dark conditions (n=48 and 96 worms, respectively) at 16 degrees C, were analyzed by LS periodograms. We obtained a 24.2+/-0.44 h period (52% of significantly rhythmic animals) in LD, and a 23.1+/-0.40 h period (37.5% of significantly rhythmic animals) under DD. The system is automateable using microcontrollers, of low-cost construction and highly reproducible. PMID:17207862

  20. The effects of nutritional polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats.

    PubMed

    Hauser, Joachim; Makulska-Gertruda, Ewelina; Reissmann, Andreas; Sontag, Thomas-A; Tucha, Oliver; Lange, Klaus W

    2014-06-01

    The present study investigated the effects of nutritional omega-3 polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats (SHRs), which are used as an animal model of attention-deficit/hyperactivity disorder (ADHD). For 6 weeks, two groups of randomly assigned SHRs received food either enriched with or deficient in omega-3 fatty acids (based on the American Institute of Nutrition-93 G/AIN93G). Using an open field, locomotor activity was subsequently assessed for 6 days. A marked difference in locomotor activity as assessed by the distance travelled in the open field was found between the two groups of rats. In comparison with rats fed with omega-3 fatty acid-enriched food, the animals on the omega-3 fatty acid-deficient diet showed a significantly higher locomotor activity. The present findings demonstrated that nutritional enrichment with omega-3 fatty acids was associated with reduced motor activity in an established animal model of ADHD and support the notion that omega-3 polyunsaturated fatty acids may play a role in the pathophysiology of ADHD. PMID:24415401

  1. Water balance and locomotor performance in three species of neotropical toads that differ in geographical distribution.

    PubMed

    Titon, Braz; Navas, Carlos Arturo; Jim, Jorge; Gomes, Fernando Ribeiro

    2010-05-01

    Water availability in the environment is a fundamental factor in determining the limits of geographical distribution and the evolution of the physiological characters associated to water balance in anurans. In this paper, we compare some aspects of water balance and the sensitivity of locomotor performance to dehydration at different temperatures for three species of toads from the genus Rhinella, with different levels of dependence on forested environments. Results show patterns associated to interspecific differences in both geographical distribution and time of seasonal reproduction. Sensitivity of locomotor performance to dehydration was lower at low temperatures for R. icterica, the species that are reproductively active during winter and lower at intermediate temperatures for R. schneideri, the species that reproduces mostly during spring, suggesting a pattern of thermal adaptation of locomotor performance for these species. Otherwise, R. ornata, a species with broader reproductive season, shows high sensitivity of locomotor performance to dehydration at all temperatures tested, suggesting a stronger relation of breeding activity with patterns of rainfall than temperature variation. Furthermore, the low rates of water uptake of R. ornata may pose restrictions on the occupation of open areas by this species. PMID:20096361

  2. Tonic Pain Experienced during Locomotor Training Impairs Retention Despite Normal Performance during Acquisition

    PubMed Central

    Bouffard, Jason; Bouyer, Laurent J.; Roy, Jean-Sébastien

    2014-01-01

    Many patients are in pain when they receive gait training during rehabilitation. Based on animal studies, it has been proposed that central sensitization associated to nociception (maladaptive plasticity) and plasticity related to the sensorimotor learning (adaptive plasticity) share similar neural mechanisms and compete with each other. The aim of this study was to evaluate whether experimental tonic pain influences motor learning (acquisition and next-day retention) of a new locomotor task. Thirty healthy human subjects performed a locomotor adaptation task (perturbing force field applied to the ankle during swing using a robotized orthosis) on 2 consecutive days. Learning was assessed using kinematic measures (peak and mean absolute plantarflexion errors) and electromyographic (EMG) activity. Half of the participants performed the locomotor adaptation task with pain on Day 1 (capsaicin cream around the ankle), while the task was performed pain-free for all subjects on Day 2 to assess retention. Pain had no significant effect on baseline gait parameters nor on performance during the locomotor adaptation task (for either kinematic or EMG measures) on Day 1. Despite this apparently normal motor acquisition, pain-free Day 2 performance was markedly and significantly impaired in the Pain group, indicating that pain during training had an impact on the retention of motor memories (interfering with consolidation and/or retrieval). These results suggest that the same motor rehabilitation intervention could be less effective if administered in the presence of pain. PMID:25009252

  3. Locomotor diversification in new world monkeys: running, climbing, or clawing along evolutionary branches.

    PubMed

    Youlatos, Dionisios; Meldrum, Jeff

    2011-12-01

    Modern platyrrhines exhibit a remarkable diversity of locomotor and postural adaptations, which evolved along multiple trajectories since the initial immigration to the island continent of South America. We trace this diversification by reviewing the available paleontological and neontological data for postcranial morphology and ecological adaptation. Fossil platyrrhines are notably diverse, from the Oligocene Branisella, to the varied Patagonian early Miocene quadurpedal-leaping and quadrupedal-climbing fossils of disputed affinities, on through the rich middle Miocene Colombian quadurpedal-leaping forms. More recent taxa exhibit even more derived positional patterns, from the largest suspensory atelids in Pleistocene Brazil, to the remarkable Antillean radiation with suspensory forms and also semiterrestrial species, with postcranial morphology convergent on some Old World monkeys. Field studies of positional behavior of modern platyrrhines set the framework for a spectrum of locomotor adaptations. Central within this spectrum is a cluster of medium-sized species with generalized locomotion (quadrupedal-leaping). At opposite poles lie the more derived conditions: large-bodied species exhibiting locomotor specializations for climbing-suspension; small-bodied species exhibiting adaptations for claw climbing and leaping. This behavior-based spectrum of locomotor diversification is similarly evident in a morphology-based pattern, that is, that produced by the shape of the talus. The implications of the record of platyrrhine postcranial evolution for the competing hypotheses of platyrrhine phylogenetic patterns, the "long lineage hypothesis" and the "stem platyrrhine hypothesis," are considered. PMID:22042747

  4. Developmental Exposure to a Dopaminergic Toxicant Produces Altered Locomotor Activity in Larval Zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after developmental exposure to various classes of prototypic drugs that act on the central nervous system. ...

  5. Posture, gait and the ecological relevance of locomotor costs and energy-saving mechanisms in tetrapods.

    PubMed

    Reilly, Stephen M; McElroy, Eric J; Biknevicius, Audrone R

    2007-01-01

    A reanalysis of locomotor data from functional, energetic, mechanical and ecological perspectives reveals that limb posture has major effects on limb biomechanics, energy-saving mechanisms and the costs of locomotion. Regressions of data coded by posture (crouched vs. erect) reveal nonlinear patterns in metabolic cost, limb muscle mass, effective mechanical advantage, and stride characteristics. In small crouched animals energy savings from spring and pendular mechanisms are inconsequential and thus the metabolic cost of locomotion is driven by muscle activation costs. Stride frequency appears to be the principal functional parameter related to the decreasing cost of locomotion in crouched animals. By contrast, the shift to erect limb postures invoked a series of correlated effects on the metabolic cost of locomotion: effective mechanical advantage increases, relative muscle masses decrease, metapodial limb segments elongate dramatically (as limbs shift from digitigrade to unguligrade designs) and biological springs increase in size and effectiveness. Each of these factors leads to decreases in the metabolic cost of locomotion in erect forms resulting from real and increasing contributions of pendular savings and spring savings. Comparisons of the relative costs and ecological relevance of different gaits reveal that running is cheaper than walking in smaller animals up to the size of dogs but running is more expensive than walking in horses. Animals do not necessarily use their cheapest gaits for their predominant locomotor activity. Therefore, locomotor costs are driven more by ecological relevance than by the need to optimize locomotor economy. PMID:17482802

  6. Self-Motion Perception during Locomotor Recalibration: More than Meets the Eye

    ERIC Educational Resources Information Center

    Durgin, Frank H.; Pelah, Adar; Fox, Laura F.; Lewis, Jed; Kane, Rachel; Walley, Katherine A.

    2005-01-01

    Do locomotor after effects depend specifically on visual feedback? In 7 experiments, 116 college students were tested, with closed eyes, at stationary running or at walking to a previewed target after adaptation, with closed eyes, to treadmill locomotion. Subjects showed faster inadvertent drift during stationary running and increased distance…

  7. From Walking to Running: Applying a Dynamical Systems Approach to the Development of Locomotor Skills.

    ERIC Educational Resources Information Center

    Whitall, Jill; Getchell, Nancy

    1995-01-01

    The locomotor skills of walking and running were compared in newly running infants at 5.5, 7.5, and 9.5 months of independent walking, and then again at 3 years of age. Collective variables showed transitional forms over the first few months of running, indicating a relatively continuous change across the two gait forms. (MDM)

  8. AGE-DEPENDENT EFFECTS OF 6-HYDROXYDOPAMINE ON LOCOMOTOR ACTIVITY IN THE RAT

    EPA Science Inventory

    This experiment examined the effects on locomotor activity of intraventricular 6-hydroxydopamine (6-OHDA) administered to developing and adult rats. 6-OHDA was administered subsequent to pargyline treatment at 3 and 6 days of age; or 6-OHDA was administered subsequent to desmethy...

  9. Dissociation of locomotor and cerebellar deficits in a murine Angelman syndrome model.

    PubMed

    Bruinsma, Caroline F; Schonewille, Martijn; Gao, Zhenyu; Aronica, Eleonora M A; Judson, Matthew C; Philpot, Benjamin D; Hoebeek, Freek E; van Woerden, Geeske M; De Zeeuw, Chris I; Elgersma, Ype

    2015-11-01

    Angelman syndrome (AS) is a severe neurological disorder that is associated with prominent movement and balance impairments that are widely considered to be due to defects of cerebellar origin. Here, using the cerebellar-specific vestibulo-ocular reflex (VOR) paradigm, we determined that cerebellar function is only mildly impaired in the Ube3am-/p+ mouse model of AS. VOR phase-reversal learning was singularly impaired in these animals and correlated with reduced tonic inhibition between Golgi cells and granule cells. Purkinje cell physiology, in contrast, was normal in AS mice as shown by synaptic plasticity and spontaneous firing properties that resembled those of controls. Accordingly, neither VOR phase-reversal learning nor locomotion was impaired following selective deletion of Ube3a in Purkinje cells. However, genetic normalization of αCaMKII inhibitory phosphorylation fully rescued locomotor deficits despite failing to improve cerebellar learning in AS mice, suggesting extracerebellar circuit involvement in locomotor learning. We confirmed this hypothesis through cerebellum-specific reinstatement of Ube3a, which ameliorated cerebellar learning deficits but did not rescue locomotor deficits. This double dissociation of locomotion and cerebellar phenotypes strongly suggests that the locomotor deficits of AS mice do not arise from impaired cerebellar cortex function. Our results provide important insights into the etiology of the motor deficits associated with AS. PMID:26485287

  10. CHARACTERIZATION OF LOCOMOTOR ACTIVITY OF ZEBRAFISH LARVAE: TEMPORAL VARIABILITY AND PHOTORESPONSE.

    EPA Science Inventory

    As part of EPA’s effort to develop a rapid, in vivo, vertebrate screen for toxic chemicals, we have begun research to characterize the locomotor activity of 6-day post-fertilization (dpf) zebrafish (Danio rerio) larvae. Larvae were individually housed and tested in 96-well micro...

  11. Effects of Cholestasis on Learning and Locomotor Activity in Bile Duct Ligated Rats

    PubMed Central

    HOSSEINI, Nasrin; ALAEI, Hojjatallah; NASEHI, Mohammad; RADAHMADI, Maryam; Mohammad Reza, ZARRINDAST

    2014-01-01

    Background: Cognitive functions are impaired in patients with liver disease. Bile duct ligation causes cholestasis that impairs liver function. This study investigated the impact of cholestasis progression on the acquisition and retention times in the passive avoidance test and on the locomotor activity of rats. Methods: Cholestasis was induced in male Wistar rats by ligating the main bile duct. Locomotor activity, learning and memory were assessed by the passive avoidance learning test at day 7, day 14, and day 21 post-bile duct ligation. The serum levels of bilirubin, alanine aminotransferase, and alkaline phosphatase were measured. Results: The results showed that acquisition time and locomotor activity were not affected at day 7 and day 14, but they were significantly (P < 0.05) impaired at day 21 post-bile duct ligation compared with the results for the control group. Additionally, memory was significantly impaired on day 7 (P < 0.01), day 14, and day 21 (P < 0.001) compared with the control groups. The levels of total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, and alkaline phosphatase were significantly higher at day 7, day 14, and day 21 post-bile duct ligation compared with the levels in the sham group. Conclusion: Based on these findings, both liver and memory function were affected in the early stage of cholestasis (7 days after bile duct ligation), while learning and locomotor activity were impaired at 21 days after bile duct ligation following the progression of cholestasis. PMID:24639608

  12. Electrical stimulation of the sural cutaneous afferent nerve controls the amplitude and onset of the swing phase of locomotion in the spinal cat

    PubMed Central

    Ollivier-Lanvin, Karen; Krupka, Alexander J.; AuYong, Nicholas; Miller, Kassi; Prilutsky, Boris I.

    2011-01-01

    Sensory feedback plays a crucial role in the control of locomotion and in the recovery of function after spinal cord injury. Investigations in reduced preparations have shown that the locomotor cycle can be modified through the activation of afferent feedback at various phases of the gait cycle. We investigated the effect of phase-dependent electrical stimulation of a cutaneous afferent nerve on the locomotor pattern of trained spinal cord-injured cats. Animals were first implanted with chronic nerve cuffs on the sural and sciatic nerves and electromyographic electrodes in different hindlimb muscles. Cats were then transected at T12 and trained daily to locomote on a treadmill. We found that electrical stimulation of the sural nerve can enhance the ongoing flexion phase, producing higher (+129%) and longer (+17.4%) swing phases of gait even at very low threshold of stimulation. Sural nerve stimulation can also terminate an ongoing extension and initiate a flexion phase. A higher prevalence of early switching to the flexion phase was observed at higher stimulation levels and if stimulation was applied in the late stance phase. All flexor muscles were activated by the stimulation. These results suggest that electrical stimulation of the sural nerve may be used to increase the magnitude of the swing phase and control the timing of its onset after spinal cord injury and locomotor training. PMID:21389308

  13. Electrical stimulation of the sural cutaneous afferent nerve controls the amplitude and onset of the swing phase of locomotion in the spinal cat.

    PubMed

    Ollivier-Lanvin, Karen; Krupka, Alexander J; AuYong, Nicholas; Miller, Kassi; Prilutsky, Boris I; Lemay, Michel A

    2011-05-01

    Sensory feedback plays a crucial role in the control of locomotion and in the recovery of function after spinal cord injury. Investigations in reduced preparations have shown that the locomotor cycle can be modified through the activation of afferent feedback at various phases of the gait cycle. We investigated the effect of phase-dependent electrical stimulation of a cutaneous afferent nerve on the locomotor pattern of trained spinal cord-injured cats. Animals were first implanted with chronic nerve cuffs on the sural and sciatic nerves and electromyographic electrodes in different hindlimb muscles. Cats were then transected at T12 and trained daily to locomote on a treadmill. We found that electrical stimulation of the sural nerve can enhance the ongoing flexion phase, producing higher (+129%) and longer (+17.4%) swing phases of gait even at very low threshold of stimulation. Sural nerve stimulation can also terminate an ongoing extension and initiate a flexion phase. A higher prevalence of early switching to the flexion phase was observed at higher stimulation levels and if stimulation was applied in the late stance phase. All flexor muscles were activated by the stimulation. These results suggest that electrical stimulation of the sural nerve may be used to increase the magnitude of the swing phase and control the timing of its onset after spinal cord injury and locomotor training. PMID:21389308

  14. Generation of Locomotor-Like Activity in the Isolated Rat Spinal Cord Using Intraspinal Electrical Microstimulation Driven by a Digital Neuromorphic CPG

    PubMed Central

    Joucla, Sébastien; Ambroise, Matthieu; Levi, Timothée; Lafon, Thierry; Chauvet, Philippe; Saïghi, Sylvain; Bornat, Yannick; Lewis, Noëlle; Renaud, Sylvie; Yvert, Blaise

    2016-01-01

    Neural prostheses based on electrical microstimulation offer promising perspectives to restore functions following lesions of the central nervous system (CNS). They require the identification of appropriate stimulation sites and the coordination of their activation to achieve the restoration of functional activity. On the long term, a challenging perspective is to control microstimulation by artificial neural networks hybridized to the living tissue. Regarding the use of this strategy to restore locomotor activity in the spinal cord, to date, there has been no proof of principle of such hybrid approach driving intraspinal microstimulation (ISMS). Here, we address a first step toward this goal in the neonatal rat spinal cord isolated ex vivo, which can display locomotor-like activity while offering an easy access to intraspinal circuitry. Microelectrode arrays were inserted in the lumbar region to determine appropriate stimulation sites to elicit elementary bursting patterns on bilateral L2/L5 ventral roots. Two intraspinal sites were identified at L1 level, one on each side of the spinal cord laterally from the midline and approximately at a median position dorso-ventrally. An artificial CPG implemented on digital integrated circuit (FPGA) was built to generate alternating activity and was hybridized to the living spinal cord to drive electrical microstimulation on these two identified sites. Using this strategy, sustained left-right and flexor-extensor alternating activity on bilateral L2/L5 ventral roots could be generated in either whole or thoracically transected spinal cords. These results are a first step toward hybrid artificial/biological solutions based on electrical microstimulation for the restoration of lost function in the injured CNS. PMID:27013936

  15. Generation of Locomotor-Like Activity in the Isolated Rat Spinal Cord Using Intraspinal Electrical Microstimulation Driven by a Digital Neuromorphic CPG.

    PubMed

    Joucla, Sébastien; Ambroise, Matthieu; Levi, Timothée; Lafon, Thierry; Chauvet, Philippe; Saïghi, Sylvain; Bornat, Yannick; Lewis, Noëlle; Renaud, Sylvie; Yvert, Blaise

    2016-01-01

    Neural prostheses based on electrical microstimulation offer promising perspectives to restore functions following lesions of the central nervous system (CNS). They require the identification of appropriate stimulation sites and the coordination of their activation to achieve the restoration of functional activity. On the long term, a challenging perspective is to control microstimulation by artificial neural networks hybridized to the living tissue. Regarding the use of this strategy to restore locomotor activity in the spinal cord, to date, there has been no proof of principle of such hybrid approach driving intraspinal microstimulation (ISMS). Here, we address a first step toward this goal in the neonatal rat spinal cord isolated ex vivo, which can display locomotor-like activity while offering an easy access to intraspinal circuitry. Microelectrode arrays were inserted in the lumbar region to determine appropriate stimulation sites to elicit elementary bursting patterns on bilateral L2/L5 ventral roots. Two intraspinal sites were identified at L1 level, one on each side of the spinal cord laterally from the midline and approximately at a median position dorso-ventrally. An artificial CPG implemented on digital integrated circuit (FPGA) was built to generate alternating activity and was hybridized to the living spinal cord to drive electrical microstimulation on these two identified sites. Using this strategy, sustained left-right and flexor-extensor alternating activity on bilateral L2/L5 ventral roots could be generated in either whole or thoracically transected spinal cords. These results are a first step toward hybrid artificial/biological solutions based on electrical microstimulation for the restoration of lost function in the injured CNS. PMID:27013936

  16. Differential Effects of Inhaled Toluene on Locomotor Activity in Adolescent and Adult Rats

    PubMed Central

    Batis, Jeffery C.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Inhalant abuse is a world-wide public health concern among adolescents. Most preclinical studies have assessed inhalant effects in adult animals leaving unclear how behavioral effects differ in younger animals. We exposed adolescent (postnatal day [PN] 28) and adult (PN90) male rats to toluene using 1 of 3 exposure patterns. These patterns modeled those reported in toluene abuse in teens and varied concentration, number and length of exposures, as well as the inter-exposure interval. Animals were exposed repeatedly over 12 days to toluene concentrations of 0, 8,000 or 16,000 parts per million (ppm). Locomotor activity was quantified during toluene exposures and for 30 min following completion of the final daily toluene exposure. For each exposure pattern, there were significant toluene concentration-related increases and decreases in locomotor activity compared to the 0-ppm “air” controls at both ages. These changes depended upon when activity was measured – during or following exposure. Compared to adults, adolescents displayed greater locomotor activity on the first day and generally greater increases in activity over days than adults during toluene exposure. Adults displayed greater locomotor activity than adolescents in the “recovery” period following exposure on the first and subsequent days. Age group differences were clearest following the pattern of paced, brief (5-min) repeated binge exposures. The results suggest that locomotor behavior in rats during and following inhalation of high concentrations of toluene depends on age and the pattern of exposure. The results are consistent with dose-dependent shifts in sensitivity and sensitization or tolerance to repeated toluene in the adolescent animals compared to the adult animals. Alternate interpretations are possible and our interpretation is limited by the range of very high concentrations of toluene used. The results imply that both pharmacological and psychosocial factors contribute to the teen

  17. Functional Reorganization of the Locomotor Network in Parkinson Patients with Freezing of Gait

    PubMed Central

    Fling, Brett W.; Cohen, Rajal G.; Mancini, Martina; Carpenter, Samuel D.; Fair, Damien A.; Nutt, John G.; Horak, Fay B.

    2014-01-01

    Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson’s disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG− and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG− patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss

  18. Oxidized trilinoleate and tridocosahexaenoate induce pica behavior and change locomotor activity.

    PubMed

    Kitamura, Fuki; Watanabe, Hiroyuki; Umeno, Aya; Yoshida, Yasukazu; Kurata, Kenji; Gotoh, Naohiro

    2013-01-01

    Pica behavior, a behavior that is characterized by eating a nonfood material such as kaolin and relates to the degree of discomfort in animals, and the variations of locomotor activity of rats after eating deteriorated fat and oil extracted from instant noodles were examined in our previous study. The result shows that oxidized fat and oil with at least 100 meq/kg in peroxide value (PV) increase pica behavior and decrease locomotor activity. In the present study, the same two behaviors were measured using autoxidized trilinoleate (tri-LA) and tridocosahexaenoate (tri-DHA) as a model of vegetable and fish oil, respectively, to compare fatty acid differences against the induction of two behaviors. The oxidized levels of tri-LA and tri-DHA were analyzed with PV and p-anisidine value (AnV), the method to analyze secondary oxidized products. The oxidation levels of respective triacylglycerol (TAG) samples were carefully adjusted to make them having almost the same PV and AnV. As the results, 600 or more meq/kg in PV of both TAGs significantly increased the consumption of kaolin pellets compared to the control group. Furthermore, 300 or more meq/kg in PV of tri-LA and 200 or more meq/kg in PV of tri-DHA demonstrated significant decrease in locomotor activity compared to control group. These results would indicate that the oxidized TAG having the same PV and/or AnV would induce the same type of pica behavior and locomotor activity. Furthermore, that the structure of oxidized products might not be important and the amount of hydroperoxide group and/or aldehyde group in deteriorated fats and oils might affect the pica behavior and locomotor activity were thought. PMID:23535307

  19. Assaying Locomotor Activity to Study Circadian Rhythms and Sleep Parameters in Drosophila

    PubMed Central

    Chiu, Joanna C.; Low, Kwang Huei; Pike, Douglas H.; Yildirim, Evrim; Edery, Isaac

    2010-01-01

    Most life forms exhibit daily rhythms in cellular, physiological and behavioral phenomena that are driven by endogenous circadian (≡24 hr) pacemakers or clocks. Malfunctions in the human circadian system are associated with numerous diseases or disorders. Much progress towards our understanding of the mechanisms underlying circadian rhythms has emerged from genetic screens whereby an easily measured behavioral rhythm is used as a read-out of clock function. Studies using Drosophila have made seminal contributions to our understanding of the cellular and biochemical bases underlying circadian rhythms. The standard circadian behavioral read-out measured in Drosophila is locomotor activity. In general, the monitoring system involves specially designed devices that can measure the locomotor movement of Drosophila. These devices are housed in environmentally controlled incubators located in a darkroom and are based on using the interruption of a beam of infrared light to record the locomotor activity of individual flies contained inside small tubes. When measured over many days, Drosophila exhibit daily cycles of activity and inactivity, a behavioral rhythm that is governed by the animal's endogenous circadian system. The overall procedure has been simplified with the advent of commercially available locomotor activity monitoring devices and the development of software programs for data analysis. We use the system from Trikinetics Inc., which is the procedure described here and is currently the most popular system used worldwide. More recently, the same monitoring devices have been used to study sleep behavior in Drosophila. Because the daily wake-sleep cycles of many flies can be measured simultaneously and only 1 to 2 weeks worth of continuous locomotor activity data is usually sufficient, this system is ideal for large-scale screens to identify Drosophila manifesting altered circadian or sleep properties. PMID:20972399

  20. Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats

    PubMed Central

    Uban, Kristina A.; Comeau, Wendy L.; Bodnar, Tamara; Yu, Wayne K.; Weinberg, Joanne; Galea, Liisa A. M.

    2014-01-01

    Rationale Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE. Methods Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1–2mg/kg) or saline-treated conditions, with injections every other day for 15 days. 14 days later, all animals received an amphetamine challenge (1mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1–29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed. Results PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (mPFC) compared to controls. Conclusions PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents w