Cue-induced reinstatement of ethanol seeking in Sardinian alcohol-preferring rats.

PubMed

Maccioni, Paola; Orrú, Alessandro; Korkosz, Agnieszka; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo; Bienkowski, Przemyslaw

2007-02-01

The purpose of the present study was to characterize cue-induced reinstatement of ethanol seeking in selectively bred Sardinian alcohol-preferring (sP) rats trained to lever press for ethanol in 30-min self-administration sessions. Four responses on an "active" lever led to presentation of 0.1 ml of 15% (vol/vol) ethanol by a liquid dipper and concurrent activation of a set of discrete light and auditory cues. In a 70-min extinction/reinstatement session, responding was first extinguished for 60 min. Subsequently, different stimuli were delivered in a noncontingent manner and reinstatement of nonreinforced responding was assessed. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup containing 5 or 15% ethanol, potently reinstated responding on the previously active lever. The magnitude of reinstatement increased with the number of stimulus presentations and concentration of ethanol presented by the dipper cup. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup filled with water (0% ethanol), did not produce any reinstatement. These results indicate that (1) noncontingent presentations of the ethanol-predictive stimulus complex may reinstate ethanol seeking in sP rats and (2) the orosensory properties of ethanol may play an important role in reinstatement of ethanol seeking in sP rats. The latter finding concurs with clinical observations that odor and taste of alcoholic beverages elicit immediate craving responses in abstinent alcoholics.

Lateral, not medial, prefrontal cortex contributes to punishment and aversive instrumental learning

PubMed Central

Jean-Richard-dit-Bressel, Philip

2016-01-01

Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral agranular insular (RAIC), prelimbic (PL), and infralimbic (IL) cortex in instrumental aversive learning and decision-making. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused mild punishment (punished lever) but continued pressing the other lever that did not cause punishment (unpunished lever). Inactivations of OFC, RAIC, IL, or PL via the GABA agonists baclofen and muscimol (BM) had no effect on the acquisition of instrumental learning. OFC inactivations increased responding on the punished lever during expression of well-learned instrumental aversive learning, whereas RAIC inactivations increased responding on the punished lever when both levers were presented simultaneously in an unpunished choice test. There were few effects of medial PFC (PL and IL) inactivation. These results suggest that lateral PFC, notably OFC and RAIC, have complementary functions in aversive instrumental learning and decision-making; OFC is important for using established aversive instrumental memories to guide behavior away from actions that cause punishment, whereas RAIC is important for aversive decision-making under conditions of choice. PMID:27918280

The effects of nicotine exposure during Pavlovian conditioning in rats on several measures of incentive motivation for a conditioned stimulus paired with water.

PubMed

Guy, Elizabeth Glenn; Fletcher, Paul J

2014-06-01

Nicotine enhances approach toward and operant responding for conditioned stimuli (CSs), but the effect of exposure during different phases of Pavlovian incentive learning on these measures remains to be determined. These studies examined the effects of administering nicotine early, late or throughout Pavlovian conditioning trials on discriminated approach behavior, nicotine-enhanced responding for conditioned reinforcement, extinction, and the reinstatement of responding for conditioned reinforcement. We also tested the effect of nicotine on approach to a lever-CS in a Pavlovian autoshaping procedure and for this CS to serve as a conditioned reinforcer. Thirsty rats were exposed to 13 conditioning sessions where a light/tone CS was paired with the delivery of water. Nicotine was administered either prior to the first or last seven sessions, or throughout the entire conditioning procedure. Responding for conditioned reinforcement, extinction, and the reinstatement of responding by the stimulus and nicotine were compared across exposure groups. Separately, the effects of nicotine on conditioned approach toward a lever-CS during autoshaping, and responding for that CS as a conditioned reinforcer, were examined. Nicotine exposure was necessary for nicotine-enhanced responding for conditioned reinforcement and the ability for nicotine and the stimulus to additively reinstate responding on the reinforced lever. Nicotine increased contacts with a lever-CS during autoshaping, and removal of nicotine abolished this effect. Prior nicotine exposure was necessary for nicotine-enhanced responding reinforced by the lever. Enhancements in the motivating properties of CSs by nicotine occur independently from duration and timing effects of nicotine exposure during conditioning.

The sensory features of a food cue influence its ability to act as an incentive stimulus and evoke dopamine release in the nucleus accumbens core

PubMed Central

Bryan, Myranda A.; Popov, Pavlo; Scarff, Raymond; Carter, Cody; Wright, Erin; Aragona, Brandon J.; Robinson, Terry E.

2016-01-01

The sensory properties of a reward-paired cue (a conditioned stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual information, resulting in CRs that vary both within and between individuals. For example, CRs include approach to the lever-CS itself (rats that “sign-track”; ST), approach to the location of reward delivery (rats that “goal-track”; GT), or an “intermediate” combination of these behaviors. We found that the multimodal sensory features of the lever-CS were important to the development and expression of sign-tracking. When the lever-CS was covered, and thus could only be heard moving, STs not only continued to approach the lever location but also started to approach the food cup during the CS period. While still predictive of reward, the auditory component of the lever-CS was a much weaker conditioned reinforcer than the visible lever-CS. This plasticity in behavioral responding observed in STs closely resembled behaviors normally seen in rats classified as “intermediates.” Furthermore, the ability of both the lever-CS and the reward-delivery to evoke dopamine release in the nucleus accumbens was also altered by covering the lever—dopamine signaling in STs resembled neurotransmission observed in rats that normally only GT. These data suggest that while the visible lever-CS was attractive, wanted, and had incentive value for STs, when presented in isolation, the auditory component of the cue was simply predictive of reward, lacking incentive salience. Therefore, the specific sensory features of cues may differentially contribute to responding and ensure behavioral flexibility. PMID:27918279

Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

PubMed Central

Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

2012-01-01

Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

Effect of short-term prefeeding and body weight on wheel running and responding reinforced by the opportunity to run in a wheel.

PubMed

Belke, Terry W; Pierce, W David; Jensen, K

2004-07-30

A biobehavioural analysis of activity anorexia suggests that the motivation for physical activity is regulated by food supply and body weight. In the present experiment, food allocation was varied within subjects by prefeeding food-deprived rats 0, 5, 10 and 15 g of food before sessions of lever pressing for wheel-running reinforcement. The experiment assessed the effects of prefeeding on rates of wheel running, lever pressing, and postreinforcement pausing. Results showed that prefeeding animals 5 g of food had no effect. Prefeeding 10 g of food reduced lever pressing for wheel running and rates of wheel running without a significant change in body weight; the effect was, however, transitory. Prefeeding 15 g of food increased the animals' body weights, resulting in a sustained decrease of wheel running and lever pressing, and an increase in postreinforcement pausing. Overall the results indicate that the motivation for physical activity is regulated by changes in local food supply, but is sustained only when there is a concomitant change in body weight.

Effects of muscimol, amphetamine, and DAMGO injected into the nucleus accumbens shell on food-reinforced lever pressing by undeprived rats.

PubMed

Stratford, Thomas R; Wirtshafter, David

2012-05-01

Previous studies have shown that large increases in food intake in nondeprived animals can be induced by injections of both the GABA(A) agonist muscimol and the μ-opioid agonist DAMGO into the nucleus accumbens shell (AcbSh), while injections of the catecholamine agonist amphetamine have little effect. In the current study we examined whether injections of these drugs are able to increase food-reinforced lever pressing in nondeprived rats. Twelve subjects were trained to lever press on a continuous reinforcement schedule while food deprived and were then tested after being placed back on ad libitum feeding. Under these conditions, responding was markedly increased by injections of either muscimol or DAMGO, although the onset of the effects of the latter drug was delayed by 30-40 min. In contrast, amphetamine injections failed to increase reinforced lever pressing, although they did enhance responding on a non-reinforced lever, presumably reflecting alterations in behavioral activation. These results demonstrate that stimulation of GABA(A) and μ-opioid receptors within the AcbSh is able to promote not only food intake, but also food-directed operant behavior. In contrast, stimulation of AcbSh dopamine receptors may enhance behavioral arousal, but does not appear to specifically potentiate behaviors directed toward food procurement. Copyright © 2012 Elsevier Inc. All rights reserved.

CHARACTERIZATION OF THE DISCRIMINATIVE STIMULUS EFFECTS OF LORCASERIN IN RATS

PubMed Central

Serafine, Katherine M.; Rice, Kenner C.; France, Charles P.

2016-01-01

Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178–1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully understand the behavioral effects of lorcaserin while considering its potential for treating substance use disorders. PMID:27640338

Wheel-running reinforcement in free-feeding and food-deprived rats.

PubMed

Belke, Terry W; Pierce, W David

2016-03-01

Rats experiencing sessions of 30min free access to wheel running were assigned to ad-lib and food-deprived groups, and given additional sessions of free wheel activity. Subsequently, both ad-lib and deprived rats lever pressed for 60s of wheel running on fixed ratio (FR) 1, variable ratio (VR) 3, VR 5, and VR 10 schedules, and on a response-initiated variable interval (VI) 30s schedule. Finally, the ad-lib rats were switched to food deprivation and the food-deprived rats were switched to free food, as rats continued responding on the response-initiated VI 30-s schedule. Wheel running functioned as reinforcement for both ad-lib and food-deprived rats. Food-deprived rats, however, ran faster and had higher overall lever-pressing rates than free-feeding rats. On the VR schedules, wheel-running rates positively correlated with local and overall lever pressing rates for deprived, but not ad-lib rats. On the response-initiated VI 30s schedule, wheel-running rates and lever-pressing rates changed for ad-lib rats switched to food deprivation, but not for food-deprived rats switched to free-feeding. The overall pattern of results suggested different sources of control for wheel running: intrinsic motivation, contingencies of automatic reinforcement, and food-restricted wheel running. An implication is that generalizations about operant responding for wheel running in food-deprived rats may not extend to wheel running and operant responding of free-feeding animals. Copyright © 2015 Elsevier B.V. All rights reserved.

Reinstatement in a Cocaine vs. Food Choice Situation: Reversal of Preference between Drug and Non-Drug Rewards

PubMed Central

Tunstall, Brendan J.; Kearns, David N.

2013-01-01

Recent studies (for review see Ahmed, 2010; 2012) show that when given a mutually exclusive choice between cocaine and food, rats almost exclusively choose food. The present experiment investigated potential shifts in preference between levers associated with either food or cocaine which might occur during extinction (food and cocaine no longer available) and during footshock-induced, cocaine-primed, and food-primed reinstatement. During self-administration sessions where food and cocaine were simultaneously available, rats demonstrated a stable food preference, choosing food over cocaine on 83% of trials. During extinction when neither reinforcer was available, no preference between levers was evident and responding decreased until rats responded on the previously food- and cocaine-associated levers at equally low rates. Footshock resulted in a non-specific reinstatement of responding upon both levers, while cocaine priming resulted in a significant preference for cocaine seeking over food seeking. This suggests that the mechanism underlying footshock-induced reinstatement is distinct from that of cocaine-primed reinstatement. Food priming engendered a mild, non-specific increase in responding on both levers. Although rats generally prefer food over cocaine when presented with a choice between these primary reinforcers, the present results suggest that in certain situations cocaine-seeking behavior prevails over food-seeking behavior. PMID:23551949

The dopamine β-hydroxylase inhibitor, nepicastat, suppresses chocolate self-administration and reinstatement of chocolate seeking in rats.

PubMed

Zaru, Alessandro; Maccioni, Paola; Colombo, Giancarlo; Gessa, Gian Luigi

2013-10-01

Craving for chocolate is a common phenomenon, which may evolve to an addictive-like behaviour and contribute to obesity. Nepicastat is a selective dopamine β-hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of cocaine seeking in rats. We verified whether nepicastat was able to modify the reinforcing and motivational properties of a chocolate solution and to prevent the reinstatement of chocolate seeking in rats. Nepicastat (25, 50 and 100 mg/kg, intraperitoneal) produced a dose-related inhibition of operant self-administration of the chocolate solution in rats under fixed-ratio 10 (FR10) and progressive-ratio schedules of reinforcement, measures of the reinforcing and motivational properties of the chocolate solution, respectively. The effect of nepicastat on the reinstatement of chocolate seeking was studied in rats in which lever-responding had been extinguished by removing the chocolate solution for approximately 8 d. Nepicastat dose-dependently suppressed the reinstatement of lever-responding triggered by a 'priming' of the chocolate solution together with cues previously associated with the availability of the reward. In a separate group of food-restricted rats trained to lever-respond for regular food pellets, nepicastat reduced FR10 lever-responding with the same potency as for the chocolate solution. Spontaneous locomotor activity was not modified by nepicastat doses that reduced self-administration of the chocolate solution and regular food pellets and suppressed the reinstatement of chocolate seeking. The results indicate that nepicastat reduces motivation to food consumption sustained by appetite or palatability. Moreover, the results suggest that DBH inhibitors may be a new class of pharmacological agents potentially useful in the prevention of relapse to food seeking in human dieters.

Characterization of the discriminative stimulus effects of lorcaserin in rats.

PubMed

Serafine, Katherine M; Rice, Kenner C; France, Charles P

2016-09-01

Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178-1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully characterize the behavioral effects of lorcaserin while considering its potential for treating substance use disorders. © 2016 Society for the Experimental Analysis of Behavior.

The effect of reinforcement differences on choice and response distribution during stimulus compounding.

PubMed

Bushnell, M C; Weiss, S J

1977-03-01

In Experiments I and II, rats were trained to respond on one lever during light and another during tone. The absence of tone and light controlled response cessation. In the multiple schedule of Experiment I, all reinforcements were received for responding in tone or light; in the chain schedule of Experiment II, all reinforcements were received in no tone + no light for not responding. Experiment I subjects, for which tone and light were associated with response and reinforcement increase, responded significantly more to tone-plus-light than to tone or light alone (additive summation). Experiment II subjects, for which tone and light were associated with response increase and reinforcement decrease, responded comparably to tone, light, and tone + light. Thus, additive summation was observed when stimulus-response and stimulus-reinforcer associations in tone and light were both positive, but not when they were conflicting. All subjects in both experiments responded predominantly on the light-correlated lever during tone + light, even when light intensity was reduced in testing. Furthermore, when a light was presented to a subject engaged in tone-associated responding, all subjects immediately switched the locus of responding to the light-correlated lever. No change in locus occurred when a tone was presented to a subject engaged in light-associated responding, irrespective of the stimulus-reinforcer association conditioned to tone. The light-lever preference in tone + light indicates that the heightened responding observed in Experiment I was not the summation of tone-associated behavior with light-associated behavior. Rather, it appears to be the result of a facilitation of one operant (light-associated responding) by the reinforcement-associated cue for the other.

Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by D-amphetamine.

PubMed

Parkinson, J A; Olmstead, M C; Burns, L H; Robbins, T W; Everitt, B J

1999-03-15

Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotor-stimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 microg) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired during the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotor-stimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.

Nicotine enhances operant responding for qualitatively distinct reinforcers under maintenance and extinction conditions.

PubMed

Barret, Scott T; Bevins, Rick A

2013-12-01

Nicotine enhancement of reward has been implicated as an important contributor to tobacco addiction. Despite the attention that reward enhancement has received, the behavioral mechanisms whereby nicotine enhances operant responding remain largely unknown. The present study sought to extend previous work by evaluating the effects of nicotine on responding for two qualitatively different rewards (visual stimulation (VS) and 4% sucrose solution) under fixed-ratio (FR) maintenance and extinction conditions. Sprague–Dawley rats were trained to press an active lever for VS (Experiment 1) or 4% sucrose solution (Experiment 2) and evaluated over 15 sessions on a FR5 schedule of reinforcement. Nicotine (0.4 mg base/kg, SC) or saline were administered 5 min before each session; the alternate solution was given in the home cage after the session. The effects of nicotine on extinction responding were then assessed over 5 sessions and rats were divided into 4 groups based on drug of injection received during FR-maintenance and extinction phases (maintenance–extinction): Nic–Nic, Nic–Sal, Sal–Sal, and Sal–Nic. Nicotine increased active lever response rates for both VS and 4% sucrose under FR5 maintenance conditions. Nicotine also increased response rates in the Nic–Nic group relative to all other groups under extinction conditions in both experiments, though this effect had greater longevity following VS maintenance conditions than sucrose. Enhancement of responding during extinction does not appear dependent upon locomotor activation by nicotine.

Effect of Light/Dark Cycle on Wheel Running and Responding Reinforced by the Opportunity to Run Depends on Postsession Feeding Time

ERIC Educational Resources Information Center

Belke, T. W.; Mondona, A. R.; Conrad, K. M.; Poirier, K. F.; Pickering, K. L.

2008-01-01

Do rats run and respond at a higher rate to run during the dark phase when they are typically more active? To answer this question, Long Evans rats were exposed to a response-initiated variable interval 30-s schedule of wheel-running reinforcement during light and dark cycles. Wheel-running and local lever-pressing rates increased modestly during…

Effects of ethanol on Pavlovian autoshaping in rats.

PubMed

Tomie, A; Cunha, C; Mosakowski, E M; Quartarolo, N M; Pohorecky, L A; Benjamin, D

1998-09-01

Approach responses, consummatory behaviors, and directed motor responses maintained by food reward resemble autoshaping CRs and are increased by lower doses of ethanol. This study evaluated the effects of presession i.p. injections of ethanol doses (0.00, 0.25, 0.50, 0.70. or 1.00 g/kg) on the acquisition of lever-press autoshaping CR performance in groups of male Long-Evans hooded rats. Paired groups received 15 daily sessions of Pavlovian autoshaping procedures, wherein the insertion of a retractable lever for 5 s (CS) was followed by the response-independent presentation of food (US). Ethanol facilitated lever-press autoshaping CR acquisition, as revealed by dose-related increases in the number of trials on which CRs were performed. The form of the dose-effect curve was inverted U-shaped with maximal responding induced during sessions 1-5 by the 0.70 g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11-15, revealing that the effects of ethanol on autoshaping CR performance were relatively stable. A pseudoconditioning control group injected presession with 0.50 g/kg ethanol received training wherein the food US was presented randomly with respect to the lever CS. Few lever-presses were performed by the Random 0.50 group, indicating that ethanol's effects on autoshaping CR acquisition and maintenance observed in the Paired 0.50 group were not due to its psychomotor activating effects. A non-injection control group performed more autoshaping CRs than did the control group injected presession with saline, indicating that daily presession i.p. injections per se suppress autoshaping CR performance. Results reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor and consummatory-like responding maintained by food reward. Implications for autoshaping accounts of impulsivity and drug abuse are considered.

Intravenous nicotine self-administration and cue-induced reinstatement in mice: Effects of nicotine dose, rate of drug infusion and prior instrumental training

PubMed Central

Fowler, Christie D.; Kenny, Paul J.

2011-01-01

Intravenous nicotine self-administration is the most direct measure of nicotine reinforcement in laboratory animals, but this procedure has proven difficult to establish in mice. We found that stable responding for nicotine in C57BL6/J mice was facilitated by prior instrumental training for food reward, initial exposure of mice to a lower unit dose of nicotine (0.03 mg/kg/infusion) before access to higher doses, a slower rate of drug delivery (3-sec versus 1-sec infusion), consistency in schedule of daily testing, and low extraneous noise during testing. Under these conditions, we found that mice lever-pressing for nicotine (0.03–0.4 mg/kg/infusion; 60-min test sessions) under a fixed-ratio 5 time-out 20-sec (FR5TO20) reinforcement schedule consumed the drug according to an inverted ‘U’-shaped dose-response curve. Mice switched their responding onto a previously non-reinforced lever to continue earning nicotine infusions when the active/inactive lever assignment was reversed. The nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine decreased responding for nicotine, but not food rewards, verifying that nAChRs regulate nicotine self-administration in mice. The cue-light paired with nicotine delivery did not support responding when delivered independently of nicotine infusions, further verifying that mice responded selectivity for the drug. Nicotine-seeking responses extinguished when nicotine infusions and the cue-light were withheld, and exposure to the cue-light reinstated responding. Finally, mice without prior instrumental food training acquired stable responding for nicotine under the FR5TO20 schedule, but required a greater number of sessions. These data demonstrate that nicotine is an effective reinforcer in mice and establish conditions under which the drug is reliably self-administered by mice. PMID:21640128

Role of ventral medial prefrontal cortex in incubation of cocaine craving

PubMed Central

Koya, Eisuke; Uejima, Jamie L.; Wihbey, Kristina A.; Bossert, Jennifer M.; Hope, Bruce T.; Shaham, Yavin

2009-01-01

Cue-induced drug-seeking in rodents progressively increases after withdrawal from cocaine, suggesting that cue-induced cocaine craving incubates over time. Here, we explored the role of the medial prefrontal cortex (mPFC, a brain area previously implicated in cue-induced cocaine seeking) in this incubation. We trained rats to self-administer cocaine for 10 d (6 h/d, infusions were paired with a tone-light cue), and then assessed after 1 or 30 withdrawal days the effect of exposure to cocaine cues on lever presses in extinction tests. We found that cue-induced cocaine-seeking in the extinction tests was higher after 30 withdrawal days than after 1 day. The time-dependent increases in extinction responding were associated with large (ventral mPFC) or modest (dorsal mPFC) increases in ERK phosphorylation (a measure of ERK activity and an index of neuronal activation). After 30 withdrawal days, ventral but not dorsal injections of muscimol+baclofen (GABAa+GABAb receptor agonists that inhibit neuronal activity) decreased extinction responding. After 1 withdrawal day, ventral but not dorsal mPFC injections of bicuculline+saclofen (GABAa+GABAb receptor antagonists that increase neuronal activity) strongly increased extinction responding. Finally, muscimol+baclofen had minimal effect on extinction responding after 1 day, and in cocaine-experienced rats, ventral mPFC injections of muscimol+baclofen or bicuculline+saclofen had no effect on lever presses for an oral sucrose solution. The present results indicate that ventral mPFC neuronal activity plays an important role in the incubation of cocaine craving. PMID:18565549

Aniracetam restores motivation reduced by satiation in a choice reaction task in aged rats.

PubMed

Nakamura, K; Kurasawa, M

2001-01-01

This study aims to examine the effects of aniracetam on satiation-induced poor performance in a choice reaction task. Aged rats that mastered the task under food restriction stably maintained the task performance for a long period. Satiation by successive free feeding greatly diminished the performance. Satiation resulted in a decreased % correct, increased % omission and prolonged choice reaction time, indicating a reduction in lever response with low choice accuracy and slow responding speed. Repeated administration of aniracetam (30 mg/kg, po, for 14 days) partially recovered the choice accuracy and lever response, but not the responding speed, task-associated motor activity or impulsivity. In addition, aniracetam did not affect the animals' weights. These results indicate that satiation reduces motivation to perform and attain the task. Aniracetam may restore motivation, probably by improving poor behavioral states (daily attentional and vigilance failures), thereby creating the driving force.

A 3-lever discrimination procedure reveals differences in the subjective effects of low and high doses of MDMA.

PubMed

Harper, David N; Langen, Anna-Lena; Schenk, Susan

2014-01-01

Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors. A three-lever drug discrimination paradigm was used. Rats were trained to respond on different levers following saline, AMPH (0.5mg/kg, IP) or MDMA (1.5mg/kg, IP) injections. Generalization curves were generated for a range of different doses of both drugs and the effect of the D1-like antagonist, SCH23390 on the discriminative stimulus effects of different doses of MDMA was determined. Rats accurately discriminated MDMA, AMPH and saline. Low doses of MDMA produced almost exclusive responding on the MDMA lever but at doses of 3.0mg/kg MDMA or higher, responding shifted to the AMPH lever. The AMPH response produced by higher doses of MDMA was attenuated by pretreatment with SCH23390. The data suggest that low doses and higher doses of MDMA produce distinct discriminative stimuli. The shift to AMPH-like responding following administration of higher doses of MDMA, and the decrease in this response following administration of SCH23390 suggests a dopaminergic component to the subjective experience of MDMA at higher doses. Copyright © 2013 Elsevier Inc. All rights reserved.

D1 receptors in the nucleus accumbens-shell, but not the core, are involved in mediating ethanol-seeking behavior of alcohol-preferring (P) rats.

PubMed

Hauser, S R; Deehan, G A; Dhaher, R; Knight, C P; Wilden, J A; McBride, W J; Rodd, Z A

2015-06-04

Clinical and preclinical research suggest that activation of the mesolimbic dopamine (DA) system is involved in mediating the rewarding actions of drugs of abuse, as well as promoting drug-seeking behavior. Inhibition of DA D1 receptors in the nucleus accumbens (Acb) can reduce ethanol (EtOH)-seeking behavior of non-selective rats triggered by environmental context. However, to date, there has been no research on the effects of D1 receptor agents on EtOH- seeking behavior of high alcohol-preferring (P) rats following prolonged abstinence. The objective of the present study was to examine the effects of microinjecting the D1 antagonist SCH 23390 or the D1 agonist A-77636 into the Acb shell or Acb core on spontaneous recovery of EtOH-seeking behavior. After 10 weeks of concurrent access to EtOH and water, P rats underwent seven extinction sessions (EtOH and water withheld), followed by 2 weeks in their home cages without access to EtOH or operant sessions. In the 2nd week of the home cage phase, rats were bilaterally implanted with guide cannula aimed at the Acb shell or Acb core; rats were allowed 7d ays to recover before EtOH-seeking was assessed by the Pavlovian Spontaneous Recovery (PSR) model. Administration of SCH23390 (1μg/side) into the Acb shell inhibited responding on the EtOH lever, whereas administration of A-77636 (0.125μg/side) increased responding on the EtOH lever. Microinfusion of D1 receptor agents into the Acb core did not alter responding on the EtOH lever. Responses on the water lever were not altered by any of the treatments. The results suggest that activation of D1 receptors within the Acb shell, but not Acb core, are involved in mediating PSR of EtOH-seeking behavior of P rats. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Dynamic Encoding of Incentive Salience in the Ventral Pallidum: Dependence on the Form of the Reward Cue.

PubMed

Ahrens, Allison M; Ferguson, Lindsay M; Robinson, Terry E; Aldridge, J Wayne

2018-01-01

Some rats are especially prone to attribute incentive salience to a cue (conditioned stimulus, CS) paired with food reward (sign-trackers, STs), but the extent they do so varies as a function of the form of the CS. Other rats respond primarily to the predictive value of a cue (goal-trackers, GTs), regardless of its form. Sign-tracking is associated with greater cue-induced activation of mesolimbic structures than goal-tracking; however, it is unclear how the form of the CS itself influences activity in neural systems involved in incentive salience attribution. Thus, our goal was to determine how different cue modalities affect neural activity in the ventral pallidum (VP), which is known to encode incentive salience attribution, as rats performed a two-CS Pavlovian conditioned approach task in which both a lever-CS and a tone-CS predicted identical food reward. The lever-CS elicited sign-tracking in some rats (STs) and goal-tracking in others (GTs), whereas the tone-CS elicited only goal-tracking in all rats. The lever-CS elicited robust changes in neural activity (sustained tonic increases or decreases in firing) throughout the VP in STs, relative to GTs. These changes were not seen when STs were exposed to the tone-CS, and in GTs there were no differences in firing between the lever-CS and tone-CS. We conclude that neural activity throughout the VP encodes incentive signals and is especially responsive when a cue is of a form that promotes the attribution of incentive salience to it, especially in predisposed individuals.

Food deprivation enhances both autoshaping and autoshaping impairment by a latent inhibition procedure.

PubMed

Sparber, S B; Bollweg, G L; Messing, R B

1991-02-01

The influence of food deprivation on acquisition of autoshaped operant behavior was measured. In one study separate groups of young, male rats that were deprived to 75%, 80%, 85%, 90%, and 95% of ad lib weight were subjected to an autoshaping procedure in which a 6 s delay was interposed between lever retraction (which occurred when rats made a lever touch, or automatically after 15 s) and food pellet delivery. In a second study, groups of rats were deprived to 80% or 90% of ad lib weight prior to testing in a latent inhibition variation of the same autoshaping procedure. This was done to determine if greater food deprivation would enhance learning which, because of the latent inhibition manipulation, is manifest as less lever-directed behavior. Greater food deprivation was associated both with fast acquisition of autoshaped lever responding and with more reliable failure to increase lever responding in the latent inhibition paradigm. Thus, increasing food deprivation was associated with enhanced acquisition regardless of whether the required performance was an increase or a failure to increase the same behavior, indicating a specific effect on learning. Copyright © 1991. Published by Elsevier B.V.

A Phaseolus vulgaris Extract Reduces Cue-Induced Reinstatement of Chocolate Seeking in Rats

PubMed Central

Lorrai, Irene; Piga, Valentina; Carai, Mauro A. M.; Riva, Antonella; Morazzoni, Paolo; Gessa, Gian Luigi; Colombo, Giancarlo; Maccioni, Paola

2016-01-01

Previous evidence has suggested that treatment with a standardized dry extract of Phaseolus vulgaris reduced intake and operant self-administration of highly palatable foods and fluids in rats and mice. The present study was designed to assess whether such extract was also effective in reducing seeking behavior for a highly hedonic chocolate-flavored beverage, using a “reinstatement” procedure adopted from the drug addiction research field and modeling relapse behavior. Rats were initially trained to lever-respond for the chocolate-flavored beverage under the Fixed Ratio (FR) 10 schedule of reinforcement. Subsequently, rats were exposed to an extinction responding phase, during which lever-responding – being unreinforced – diminished progressively up to extinction. Lever-responding was then powerfully reinstated by the non-contingent presentation of a complex of gustatory, olfactory, auditory, and visual stimuli previously associated to the availability of the chocolate-flavored beverage. Acute, intragastric administration of P. vulgaris dry extract (100 and 500 mg/kg) reduced lever-responding by 40–45%, in comparison to vehicle condition. These results indicate the ability of P. vulgaris dry extract to reduce seeking behavior for a highly palatable nourishment in an experimental model of relapse into disordered eating of palatable foods. The unavailability of the chocolate-flavored beverage in the reinstatement session tends to exclude that the observed effect of the P. vulgaris dry extract was secondary to any inhibition of carbohydrate metabolism; conversely, it is the likely consequence on a central action on the rewarding and hedonic properties of food. PMID:27199752

Reinstatement of MDMA (ecstasy) seeking by exposure to discrete drug-conditioned cues

PubMed Central

Ball, Kevin T.; Walsh, Kelly M.; Rebec, George V.

2007-01-01

The widely used recreational drug MDMA (ecstasy) supports self-administration in animals, but it is not known whether MDMA-associated cues are able to reinstate drug seeking in a relapse model of drug addiction. To assess this possibility, drug-naïve rats were trained to press a lever for MDMA infusions (0.30 mg/kg/infusion, i.v.) paired with a compound cue (light and tone) in daily 2 hr sessions. Responding was reinforced contingent on a modified fixed-ratio 5 schedule of reinforcement. Conditioned cue-induced reinstatement tests were conducted after lever pressing was extinguished in the absence of MDMA and the conditioned cues. Conditioned cues reinstated lever pressing after extinction, and the magnitude of reinstatement was positively correlated with the level of responding during MDMA self-administration. These results show for the first time that conditioned cues can trigger reinstatement of MDMA-seeking behavior in rats, and that individual differences in the pattern of MDMA self-administration can predict the magnitude of reinstatement responding. PMID:17602729

Effects of exposure to 56Fe particles or protons on fixed-ratio operant responding in rats

NASA Technical Reports Server (NTRS)

Rabin, Bernard M.; Buhler, Lynn L.; Joseph, James A.; Shukitt-Hale, Barbara; Jenkins, Daniel G.

2002-01-01

On long-duration trips outside of the magnetosphere, astronauts will be exposed to protons and to heavy particles which can affect their performance of required tasks. It is essential to determine the range of behaviors that might be affected by exposure to these types of radiation in order to understand the nature of behavioral deficits and to develop effective countermeasures. The present experiment examined the ability of rats to make an operant response following exposure to protons (250 MeV, 4 Gy) or 56Fe particles (1 GeV/n, 1 or 2 Gy). Following irradiation, rats were trained to press a lever in order to obtain food reinforcement. They were then placed on an ascending fixed-ratio schedule from FR-1 (each lever press rewarded with a food pellet) through FR-35 (35 lever presses required for 1 food pellet). Rats exposed to 4 Gy of protons or 1 Gy of 56Fe particles responded similarly to controls, increasing their rate of responding as the ratio increased. However, rats exposed to 2 Gy of 56Fe particles failed to increase their rate of responding at ratios greater than FR-20, indicating that rats exposed to 2 Gy of 56Fe particles cannot respond appropriately to increasing work requirements.

Paired-housing selectively facilitates within-session extinction of avoidance behavior, and increases c-Fos expression in the medial prefrontal cortex, in anxiety vulnerable Wistar-Kyoto rats.

PubMed

Smith, Ian M; Pang, Kevin C H; Servatius, Richard J; Jiao, Xilu; Beck, Kevin D

2016-10-01

The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC). One means of reducing physiological responses to anxiety, and conditioned fear, in social species is the presence of a conspecific animal. The current study investigates whether or not pair-housed WKY rats would show facilitated extinction of avoidance in comparison to individual-housed WKY rats, and whether or not pair-housing influences mPFC activation during lever-press avoidance. Male WKY rats were assigned to individual-housed and pair-housed conditions. Rats were trained in lever-press avoidance. Each session of lever-press avoidance consisted of 20 trials, where pressing a lever in response to a warning tone prevented foot-shocks. Rats received 12 acquisition sessions over 4weeks; followed by 6 extinction sessions over 2weeks, where foot-shocks ceased to be delivered. Brains were harvested 90min after trials 1 and 10 of extinction sessions 1 and 6, and mPFC sections underwent c-Fos staining as a measure of activation. Pair-housed rats showed facilitated lever-press avoidance extinction rates, but the main cause for this overall difference was a selective facilitation of within-session extinction. Similar to individual-housed rats, pair-housed rats continued to avoid during trial 1 of extinction even when the avoidance responding had been significantly reduced by the end of the previous session. Pair-housed rats sacrificed on trial 1 showed greater c-Fos expression in the anterior cingulate cortex and prelimbic cortex subregions of the mPFC compared individual-housed rats sacrificed on trial 1. This data shows pair-housing to facilitate the extinction of avoidance, and to influence activity of the mPFC, in WKY rats. Despite this environmental manipulation, the pair-housed WKY rats continued to show avoidance responding on trial 1 of extinction sessions. This demonstrates that within-session extinction can be dissociated from between-session extinction-resistance in WKY rats. Furthermore, it suggests the individual-housing of WKY rats selectively slows within-session extinction, possibly by reducing neuronal activity of the mPFC during the testing situation. Published by Elsevier Inc.

Autoshaping, random control, and omission training in the rat1

PubMed Central

Locurto, Charles; Terrace, H. S.; Gibbon, John

1976-01-01

The role of the stimulus-reinforcer contingency in the development and maintenance of lever contact responding was studied in hooded rats. In Experiment I, three groups of experimentally naive rats were trained either on autoshaping, omission training, or a random-control procedure. Subjects trained by the autoshaping procedure responded more consistently than did either random-control or omission-trained subjects. The probability of at least one lever contact per trial was slightly higher in subjects trained by the omission procedure than by the random-control procedure. However, these differences were not maintained during extended training, nor were they evident in total lever-contact frequencies. When omission and random-control subjects were switched to the autoshaping condition, lever contacts increased in all animals, but a pronounced retardation was observed in omission subjects relative to the random-control subjects. In addition, subjects originally exposed to the random-control procedure, and later switched to autoshaping, acquired more rapidly than naive subjects that were exposed only on the autoshaping procedure. In Experiment II, subjects originally trained by an autoshaping procedure were exposed either to an omission, a random-control, or an extinction procedure. No differences were observed among the groups either in the rate at which lever contacts decreased or in the frequency of lever contacts at the end of training. These data implicate prior experience in the interpretation of omission-training effects and suggest limitations in the influence of stimulus-reinforcer relations in autoshaping. PMID:16811960

Autoshaping, random control, and omission training in the rat.

PubMed

Locurto, C; Terrace, H S; Gibbon, J

1976-11-01

The role of the stimulus-reinforcer contingency in the development and maintenance of lever contact responding was studied in hooded rats. In Experiment I, three groups of experimentally naive rats were trained either on autoshaping, omission training, or a random-control procedure. Subjects trained by the autoshaping procedure responded more consistently than did either random-control or omission-trained subjects. The probability of at least one lever contact per trial was slightly higher in subjects trained by the omission procedure than by the random-control procedure. However, these differences were not maintained during extended training, nor were they evident in total lever-contact frequencies. When omission and random-control subjects were switched to the autoshaping condition, lever contacts increased in all animals, but a pronounced retardation was observed in omission subjects relative to the random-control subjects. In addition, subjects originally exposed to the random-control procedure, and later switched to autoshaping, acquired more rapidly than naive subjects that were exposed only on the autoshaping procedure. In Experiment II, subjects originally trained by an autoshaping procedure were exposed either to an omission, a random-control, or an extinction procedure. No differences were observed among the groups either in the rate at which lever contacts decreased or in the frequency of lever contacts at the end of training. These data implicate prior experience in the interpretation of omission-training effects and suggest limitations in the influence of stimulus-reinforcer relations in autoshaping.

Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats.

PubMed

Baladi, Michelle G; Newman, Amy H; France, Charles P

2014-02-01

The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine. Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine. Apomorphine, quinpirole, and lisuride occasioned >90 % responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90 % responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats. These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures.

Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats

PubMed Central

Baladi, Michelle G; Newman, Amy H; France, Charles P

2013-01-01

Rationale The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. Objective This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine. Method Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine. Result Apomorphine, quinpirole, and lisuride occasioned >90% responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90% responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats. Conclusion These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures. PMID:24030470

Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol self-administration of alcohol-preferring (P) rats.

PubMed

Rodd, Zachary A; Bell, Richard L; Oster, Scott M; Toalston, Jamie E; Pommer, Tylene J; McBride, William J; Murphy, James M

2010-05-01

Several studies indicated the involvement of serotonin-3 ([5-hydroxy tryptamine] 5-HT(3)) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT(3) receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers (Coulbourn Instruments, Allentown, PA) were used to examine the effects of seven consecutive bilateral microinfusions of ICS 205-930 (ICS), a 5-HT(3) receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (vol/vol) ethanol self-administration. P rats readily acquired ethanol self-administration by the fourth session. The three highest doses (0.125, 0.25, and 1.25 microg) of ICS prevented acquisition of ethanol self-administration. During the acquisition postinjection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the three highest doses (0.75, 1.0, and 1.25 microg) of ICS significantly increased responding on the ethanol lever; after the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Microinfusion of ICS into the posterior VTA did not alter the low responding on the water lever and did not alter saccharin (0.0125% wt/v) self-administration. Microinfusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT(3) receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration and/or repeated treatments with a 5-HT(3) receptor antagonist may alter neuronal circuitry within the posterior VTA. 2010 Elsevier Inc. All rights reserved.

Effects of repeated administration of the monoamine oxidase inhibitor phenelzine on the discriminability of d-lysergic acid diethylamide (LSD) and 1-(m-trifluoromethylphenyl) piperazine (TFMPP).

PubMed

Cunningham, K A; Carroll, B A; Appel, J B

1986-01-01

Rats trained to discriminate d-lysergic acid diethylamide (LSD; 0.08 mg/kg) or 1-(m-trifluoromethylphenyl) piperazine (TFMPP; 0.8 mg/kg) were treated with the monoamine oxidase inhibitor (MAOI) phenelzine (10 mg/kg/day) for 7 days. After a 24 h "washout" period, they were challenged with the training drug (and dose) or saline, during extinction test sessions. Following 0.08 mg/kg LSD, LSD-trained rats responded primarily on the saline lever (29% drug-appropriate responding) while, after TFMPP (0.8 mg/kg), TFMPP-trained animals responded on the drug lever (75% drug-appropriate responding). These preliminary data suggest that, if serotonin receptors are involved in the behavioral effects of TFMPP, these receptors differ from those involved in the effects of LSD.

PUNISHING AND CARDIOVASCULAR EFFECTS OF INTRAVENOUS HISTAMINE IN RATS: PHARMACOLOGICAL SELECTIVITY

PubMed Central

Podlesnik, Christopher A.; Jimenez-Gomez, Corina

2014-01-01

Although drugs may serve as reinforcers or punishers of operant behavior, the punishing function has received much less experimental attention than the reinforcing function. A sensitive method for studying drug-induced punishment is to assess choice for a punished response over an unpunished response. In these experiments, rats chose between pressing one lever and receiving a sucrose pellet or pressing another lever and receiving a sucrose pellet plus an intravenous injection of histamine. When sucrose was delivered equally frequently for either the punished or the unpunished response, rats selected the unpunished lever consistently, but decreases in the punished response did not differ as a function of intravenous histamine dose (0.1–1 mg/kg/inj). Changing the procedure so that sucrose was delivered on the unpunished lever with p = .5 increased the rats’ responding on the punished lever with saline injections. In addition, the same range of histamine doses produced a much larger range of responses on the punished lever that was dose dependent. Using these procedures to assess the receptors mediating histamine’s effects, the histamine H1-receptor antagonists, pyrilamine and ketotifen, antagonized the punishing effect of histamine, but the histamine H2-receptor antagonist ranitidine did not. However, ranitidine pretreatments reduced histamine-induced heart-rate increases to a greater extent than did the histamine H1-receptor antagonists when administered at the same doses examined under conditions of histamine punishment. Overall, the present findings extend the general hypothesis that activation of histamine H1-receptors mediates the punishing effects of histamine. They also introduce methods for rapidly assessing pharmacological mechanisms underlying drug-induced punishment. PMID:23982898

An analysis of policy levers used to implement mental health reform in Australia 1992-2012.

PubMed

Grace, Francesca C; Meurk, Carla S; Head, Brian W; Hall, Wayne D; Carstensen, Georgia; Harris, Meredith G; Whiteford, Harvey A

2015-10-24

Over the past two decades, mental health reform in Australia has received unprecedented government attention. This study explored how five policy levers (organisation, regulation, community education, finance and payment) were used by the Australian Federal Government to implement mental health reforms. Australian Government publications, including the four mental health plans (published in 1992, 1998, 2003 and 2008) were analysed according to policy levers used to drive reform across five priority areas: [1] human rights and community attitudes; [2] responding to community need; [3] service structures; [4] service quality and effectiveness; and [5] resources and service access. Policy levers were applied in varying ways; with two or three levers often concurrently used to implement a single initiative or strategy. For example, changes to service structures were achieved using various combinations of all five levers. Attempts to improve service quality and effectiveness were instead made through a single lever-regulation. The use of some levers changed over time, including a move away from prescriptive, legislative use of regulation, towards a greater focus on monitoring service standards and consumer outcomes. Patterns in the application of policy levers across the National Mental Health Strategy, as identified in this analysis, represent a novel way of conceptualising the history of mental health reform in Australia. An improved understanding of the strategic targeting and appropriate utilisation of policy levers may assist in the delivery and evaluation of evidence-based mental health reform in the future.

Assessing the Role of Effort Reduction in the Reinforcing Efficacy of Timeout from Avoidance

ERIC Educational Resources Information Center

Galuska, Chad M.; Mikorski, Jeff; Perone, Michael

2012-01-01

Rats responded on concurrent schedules of shock-postponement or deletion (avoidance) and timeout from avoidance. In Experiment 1, 3 rats' responses on one lever postponed shocks for 20 s and responses on a second lever produced a 1-min timeout according to a variable-interval 45-s schedule. Across conditions, a warning signal (white noise) was…

Learning not to respond: Role of the hippocampus in withholding responses during omission training.

PubMed

White, Norman M; Naeem, Maliha

2017-02-01

Autoshaping is a Pavlovian learning paradigm in which rats experience pairings of a CS and a US independently of their behavior. When the CS is a lever inserted into the test cage and the US is food delivered to an adjacent magazine, many rats acquire a lever-pressing response called 'sign-tracking' even though that response has no effect on the occurrence of either the CS or the US. Since these lever presses are always followed by the US, it has been suggested that sign-tracking could be due to unintended reinforcement of the response. To eliminate the possibility of such instrumental learning the omission schedule, in which a response to the CS cancels the US, was introduced. Previous research has shown that training rats on autoshaping and switching them to an omission schedule generally reduces but does not eliminate sign-tracking, suggesting that it may be due to both Pavlovian and instrumental learning. In the present study naive rats trained on an omission schedule sign-tracked less than a control group exposed to random, unpaired CS and US presentations, suggesting that they learned to withhold the lever press response because of the negative contingency between that response and the US. In a second experiment rats with dorsal hippocampus lesions sign-tracked more than sham-lesioned rats on omission schedules, suggesting that this case of learning not to respond is hippocampus-based. This conclusion is consistent with many previous findings on the inability of hippocampal rats to withhold or suppress responding, and with studies suggesting that one form of extinction of learned responses in normal rats is due to competition from hippocampus-based learning not to respond. Copyright © 2016 Elsevier B.V. All rights reserved.

Shoulder Muscular Demand During Lever-Activated Vs Pushrim Wheelchair Propulsion in Persons With Spinal Cord Injury

PubMed Central

Requejo, Philip Santos; Lee, Sharon E; Mulroy, Sara J; Haubert, Lisa Lighthall; Bontrager, Ernest L; Gronley, JoAnne K; Perry, Jacquelin

2008-01-01

Background/Objective: The high demand on the upper limbs during manual wheelchair (WC) use contributes to a high prevalence of shoulder pathology in people with spinal cord injury (SCI). Lever-activated (LEVER) WCs have been presented as a less demanding alternative mode of manual WC propulsion. The objective of this study was to evaluate the shoulder muscle electromyographic activity and propulsion characteristics in manual WC users with SCI propelling a standard pushrim (ST) and LEVER WC design. Methods: Twenty men with complete injuries (ASIA A or B) and tetraplegia (C6, n = 5; C7, n = 7) or paraplegia (n = 8) secondary to SCI propelled ST and LEVER WCs at 3 propulsion conditions on a stationary ergometer: self-selected free, self-selected fast, and simulated graded resistance. Average velocity, cycle distance, and cadence; median and peak electromyographic intensity; and duration of electromyography of anterior deltoid, pectoralis major, supraspinatus, and infraspinatus muscles were compared between LEVER and ST WC propulsion. Results: Significant decreases in pectoralis major and supraspinatus activity were recorded during LEVER compared with ST WC propulsion. However, anterior deltoid and infraspinatus intensities tended to increase during LEVER WC propulsion. Participants with tetraplegia had similar or greater anterior deltoid, pectoralis major, and infraspinatus activity for both ST and LEVER WC propulsion compared with the men with paraplegia. Conclusions: Use of the LEVER WC reduced and shifted the shoulder muscular demands in individuals with paraplegia and tetraplegia. Further studies are needed to determine the impact of LEVER WC propulsion on long-term shoulder function. PMID:19086715

Contributions of basolateral amygdala and nucleus accumbens subregions to mediating motivational conflict during punished reward-seeking.

PubMed

Piantadosi, Patrick T; Yeates, Dylan C M; Wilkins, Mathew; Floresco, Stan B

2017-04-01

The involvement of different nodes within meso-cortico-limbic-striatal circuitry in mediating reward-seeking has been well described, yet comparatively less is known about how such circuitry may regulate appetitively-motivated behaviors that may be punished. The basolateral amygdala (BLA) is one nucleus that has been implicated in suppressing punished reward-seeking, and this structure can modulate goal-directed behavior via projections to subregions of the nucleus accumbens (NAc). Here, we examined the effects of reversible inactivations of the BLA, NAc Shell (NAcS), and core (NAcC) on performance of a "Conflict" task where rats pressed a lever for sucrose reinforcement during three distinct 5min phases. During the first and last phases of a session, rats lever-pressed for food reward delivered on a VI-15/FR5 schedule. In between these phases was a signaled "Conflict" period, where each lever-press yielded food, but 50% of presses were also punished with foot-shock. Under control conditions, well-trained rats responded vigorously during the two "safe" VI-15/FR5 periods, but reduced responding during the punished Conflict period. Inactivation of either the BLA or the NAcS via infusions of baclofen/muscimol disinhibited punished seeking, increasing lever-pressing during the conflict period, while attenuating pressing during VI-15/FR5 phases. In contrast, NAcC inactivation markedly decreased responding across all three phases. Similar inactivation of the BLA or NAcS did not alter responding in a separate control experiment where rats pressed for food on schedules identical to the Conflict task in the absence of any punishment, while NAcC inactivation again suppressed responding. These results imply that BLA and NAcS are part of a circuit that suppresses reward-seeking in the face of danger, which in turn may have implications for disorders characterized by punishment resistance, including substance abuse and obsessive-compulsive disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

Oral operant ethanol self-administration in the absence of explicit cues, food restriction, water restriction and ethanol fading in C57BL/6J mice

PubMed Central

Stafford, Alexandra M.; Anderson, Shawn M.; Shelton, Keith L.; Brunzell, Darlene H.

2015-01-01

Rationale Mouse models of EtOH self-administration are useful to identify genetic and biological underpinnings of alcohol use disorder. Objectives These experiments developed a novel method of oral operant EtOH self-administration in mice without explicitly paired cues, food/water restriction, or EtOH fading. Methods Following magazine and lever training for 0.2% saccharin (SAC), mice underwent 9 weekly overnight sessions with lever pressing maintained by dipper presentation of 0, 3, 10 or 15% EtOH in SAC or water vehicle. Ad libitum water was available from a bottle. Results Water vehicle mice ingested most fluid from the water bottle in contrast to SAC vehicle mice, which despite lever pressing demands, drank most of their fluid from the liquid dipper. Although EtOH in SAC vehicle mice showed concentration-dependent increases of g/kg EtOH intake, lever pressing decreased with increasing EtOH concentration and did not exceed that of SAC vehicle alone at any EtOH concentration. Mice reinforced with EtOH in water ingested less EtOH than mice reinforced with EtOH in SAC. EtOH in water mice, however, showed concentration-dependent increases in g/kg EtOH intake and lever presses. 15% EtOH in water mice showed significantly greater levels of lever pressing than water vehicle mice and a significant escalation of responding across weeks of exposure. Naltrexone pretreatment reduced EtOH self-administration and intake in these mice without altering responding in the vehicle control condition during the first hour of the session. Conclusions SAC facilitated EtOH intake but prevented observation of EtOH reinforcement. Water vehicle unmasked EtOH's reinforcing effects. PMID:26268145

Oral operant ethanol self-administration in the absence of explicit cues, food restriction, water restriction and ethanol fading in C57BL/6J mice.

PubMed

Stafford, Alexandra M; Anderson, Shawn M; Shelton, Keith L; Brunzell, Darlene H

2015-10-01

Mouse models of ethanol (EtOH) self-administration are useful to identify genetic and biological underpinnings of alcohol use disorder. These experiments developed a novel method of oral operant EtOH self-administration in mice without explicitly paired cues, food/water restriction, or EtOH fading. Following magazine and lever training for 0.2 % saccharin (SAC), mice underwent nine weekly overnight sessions with lever pressing maintained by dipper presentation of 0, 3, 10, or 15 % EtOH in SAC or water vehicle. Ad libitum water was available from a bottle. Water vehicle mice ingested most fluid from the water bottle in contrast to SAC vehicle mice, which despite lever pressing demands, drank most of their fluid from the liquid dipper. Although EtOH in SAC vehicle mice showed concentration-dependent increases of g/kg EtOH intake, lever pressing decreased with increasing EtOH concentration and did not exceed that of SAC vehicle alone at any EtOH concentration. Mice reinforced with EtOH in water ingested less EtOH than mice reinforced with EtOH in SAC. EtOH in water mice, however, showed concentration-dependent increases in g/kg EtOH intake and lever presses. Fifteen percent EtOH in water mice showed significantly greater levels of lever pressing than water vehicle mice and a significant escalation of responding across weeks of exposure. Naltrexone pretreatment reduced EtOH self-administration and intake in these mice without altering responding in the vehicle control condition during the first hour of the session. SAC facilitated EtOH intake but prevented observation of EtOH reinforcement. Water vehicle unmasked EtOH's reinforcing effects.

Rats' Memory for Time and Relational Responding in the Duration-Comparison Procedure

ERIC Educational Resources Information Center

Santi, Angelo; Hoover, Claire; Simmons, Sabrina

2011-01-01

Rats were trained in a duration-comparison task to press one lever if the comparison duration ("c") was 1.2-s shorter than a standard duration ("s"), and another lever if c was 1.2-s longer than s. The interval between s and c duration was 1 s. The 10 duration pairs used during training controlled for the absolute duration of "c" and the total…

Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses

PubMed Central

Nett, Kelle E.; Cosme, Caitlin V.; Worth, Wensday R.; Wemmie, John A.

2017-01-01

The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period. SIGNIFICANCE STATEMENT The infralimbic cortex (IL) contributes to the extinction of cocaine-seeking behavior, but the precise relationship among IL activity, lever pressing during extinction, and extinction learning has not been elucidated using traditional methods. Using a closed-loop optogenetic approach, we found that selective inhibition of the IL immediately after unreinforced lever pressing impaired within-session extinction learning and promoted the subsequent cued reinstatement of cocaine seeking. These studies suggest that IL activity immediately after the instrumental response during extinction learning of cocaine seeking encodes information required for such learning and that altering such activity produces long-lasting changes in subsequent measures of cocaine craving/relapse. PMID:28539416

Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses.

PubMed

Gutman, Andrea L; Nett, Kelle E; Cosme, Caitlin V; Worth, Wensday R; Gupta, Subhash C; Wemmie, John A; LaLumiere, Ryan T

2017-06-21

The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period. SIGNIFICANCE STATEMENT The infralimbic cortex (IL) contributes to the extinction of cocaine-seeking behavior, but the precise relationship among IL activity, lever pressing during extinction, and extinction learning has not been elucidated using traditional methods. Using a closed-loop optogenetic approach, we found that selective inhibition of the IL immediately after unreinforced lever pressing impaired within-session extinction learning and promoted the subsequent cued reinstatement of cocaine seeking. These studies suggest that IL activity immediately after the instrumental response during extinction learning of cocaine seeking encodes information required for such learning and that altering such activity produces long-lasting changes in subsequent measures of cocaine craving/relapse. Copyright © 2017 the authors 0270-6474/17/376075-12$15.00/0.

Suppressing effect of COR659 on alcohol, sucrose, and chocolate self-administration in rats: involvement of the GABAB and cannabinoid CB1 receptors.

PubMed

Maccioni, Paola; Colombo, Giancarlo; Lorrai, Irene; Zaru, Alessandro; Carai, Mauro A M; Gessa, Gian Luigi; Brizzi, Antonella; Mugnaini, Claudia; Corelli, Federico

2017-09-01

COR659 [methyl2-(4-chlorophenylcarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate] is a new, positive allosteric modulator (PAM) of the GABA B receptor. This study evaluated whether COR659 shared with previously tested GABA B PAMs the capacity to reduce alcohol self-administration in rats. Treatment with non-sedative doses of COR659 (2.5, 5, and 10 mg/kg; i.p.) suppressed lever-responding for alcohol (15% v/v) in Sardinian alcohol-preferring (sP) rats under the fixed ratio (FR) 4 (FR4) and progressive ratio (PR) schedules of reinforcement; COR659 was more potent and effective than the reference GABA B PAM, GS39783. Treatment with COR659, but not GS39783, suppressed (a) lever-responding for a sucrose solution (1-3% w/v) in sP rats under the FR4 and PR schedules, (b) lever-responding for a chocolate solution [5% (w/v) Nesquik®] in Wistar rats under the FR10 and PR schedules, and (c) cue-induced reinstatement of chocolate seeking in Wistar rats. Treatment with COR659 was completely ineffective on lever-responding (FR10) for regular food pellets in food-deprived Wistar rats. Pretreatment with the GABA B receptor antagonist, SCH50911, partially blocked COR659-induced reduction of alcohol self-administration, being ineffective on reduction of chocolate self-administration. Pretreatment with the cannabinoid CB 1 receptor antagonist, AM4113, fully blocked COR659-induced reduction of chocolate self-administration, being ineffective on reduction of alcohol self-administration. COR659 might exert its behavioral effects via a composite mechanism: (i) positive allosteric modulation of the GABA B receptor, responsible for a large proportion of reduction of alcohol self-administration; (ii) an action at other receptor system(s), including the cannabinoid CB 1 receptor, through which COR659 affects seeking and consumption of highly palatable foods.

The effects of psychotomimetics and psychomotor stimulants on two schedules promoting response switching in the rat.

PubMed

Evenden, John

2002-10-01

Psychosis and psychotomimetic drugs result in a disorganisation of the structure of thought and behaviour. Normalising these is one of the objects of antipsychotic therapy, and methods for predicting such a therapeutic effect would be of value. The effects of a number of psychotomimetic agents were examined on the way in which rats distributed responding over two response levers using two different procedures, to assay their effects on behavioural organisation. Previously, amphetamine has been found to increase response switching using these schedules. In the first, the random reinforcement procedure, one of the two levers was selected at random as "correct", and responses on this lever were reinforced with food under a random ratio schedule. No signal was given to distinguish the levers. Responding could also result in the food tray being illuminated, but no food pellet was delivered ("no-food" event). Responses on the second lever ("incorrect") had no programmed consequences. After each food delivery or "no-food" event the levers designated as "correct" and "incorrect" were reassigned at random, and the rat had to open the food tray to restart the schedule. In the second procedure, the rats were required to make 21 responses before a switch between the two levers resulted in food delivery [Fixed Ratio (FR) 21-switch]. The responses making up the FR could be distributed freely between the two levers. Phencyclidine (PCP), scopolamine, caffeine and ethanol increased switching under the random reinforcement procedure, but (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and atropine did not. PCP, caffeine, lysergic acid diethylamide (LSD) and atropine increased switching under the FR21-switch procedure, but ethanol did not. The increases in switching produced by PCP, LSD and the anticholinergics were accompanied by marked reductions in response rate, whereas those produced by amphetamine and caffeine were not. The effects of amphetamine, and PCP were strongly dependent on the baseline probability of switching, those of atropine and caffeine moderately so, and those of LSD and ethanol only weakly so. Of the agents tested, psychomotor stimulants appear to produce the most selective increases in switching. The procedures described here may be useful for assaying the disorganisation of behaviour produced by other psychotomimetics and may have value in the detection of novel antipsychotic drugs.

Autoshaping in micrencephalic rats.

PubMed

Goldstein, L H; Oakley, D A

1989-06-01

An autoshaping procedure in which the illumination of a lever was predictive of food reinforcement was used to compare learning in rats with micrencephaly induced by irradiation on the 16th day of gestation and in sham-irradiated controls. Both groups showed equivalent levels of lever-directed activity, and the micrencephalic animals differentiated as well as the control animals between the predictive lever and a nonpredictive lever. The micrencephalic animals were able to redistribute their lever-directed activity when the significance of the levers was reversed and did so more readily than the control animals. Results support the claim that association learning survives either traumatic or developmental neocortical damage and have implications for remedial procedures following both head injury and developmental cerebral pathology in humans.

Reduction by the Positive Allosteric Modulator of the GABAB Receptor, GS39783, of Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats Exposed to the “Sipper” Procedure

PubMed Central

Maccioni, Paola; Flore, Paolo; Carai, Mauro A. M.; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

2010-01-01

The present study was designed to evaluate (a) alcohol self-administration behavior of selectively bred, Sardinian alcohol-preferring (sP) rats exposed to the so-called “sipper” procedure (characterized by the temporal separation between alcohol-seeking and -taking phases), and (b) the effect of the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in sP rats exposed to this procedure. To this end, sP rats were initially trained to lever-respond under a reinforcement requirement (RR) 55 (RR55) for alcohol. Achievement of RR55 resulted in the 20-min presentation of the alcohol (15%, v/v)-containing sipper bottle. Once stable levels of lever-responding and alcohol consumption were reached, rats were treated with 0, 25, 50, and 100 mg/kg GS39783 (i.g.) 60 min before the self-administration session. Rats displayed robust alcohol-seeking (as suggested by relatively short latencies to the first lever-response and high frequencies of lever-responding) and -taking (as suggested by alcohol intakes averaging approximately 1.5 g/kg) behaviors. Pretreatment with GS39783 inhibited both alcohol-seeking (the number of rats achieving RR55 and the mean RR value were virtually halved) and -taking (the amount of self-administered alcohol was reduced by approximately 60%). The results of the present study suggest the power of the “sipper” procedure in triggering high levels of alcohol-seeking and -taking behavior in sP rats. Further, these results extend to this additional procedure of alcohol self-administration the capacity of GS39783 to reduce the motivational properties of alcohol and alcohol consumption in sP rats. PMID:21423431

Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs)

PubMed Central

Sable, Helen J. K.; Monaikul, Supida; Poon, Emily; Eubig, Paul A.; Schantz, Susan L.

2010-01-01

Polychlorinated biphenyls (PCBs) are environmental neurotoxicants known to affect the brain dopaminergic (DA) system. This project investigated whether developmental exposure to PCBs would alter the discriminative stimulus effects of psychostimulant drugs known to act on the DA system. Female Long-Evans rats were orally exposed to 0, 3, or 6 mg/kg/day of an environmentally relevant PCB mixture from four weeks prior to breeding through weaning of their litters on PND 21. When they reached adulthood one male and female/litter were trained to discriminate cocaine (10.0 mg/kg, IP) from saline by repeatedly pairing cocaine injections with reinforcement on one operant response lever, and saline injections with reinforcement on the other lever. After response training, generalization tests to four lower doses of cocaine (7.5, 5.0, 2.5, and 1.25 mg/kg, IP) and to amphetamine (1.0, 0.5, 0.25, and 0.125 mg/kg, IP) were given two days/week, with additional training dose days in-between. Percent responding of the PCB-exposed rats on the cocaine-paired lever was significantly higher than that of controls for the highest generalization dose of cocaine, and lower than that of controls for the highest dose of amphetamine. Response rate and percent responding on the cocaine lever did not differ among the exposure groups on the days when the training dose of cocaine was given, suggesting the generalization test results were not due to pre-existing differences in discrimination ability or rate of responding. These findings suggest developmental PCB exposure can alter the interoceptive cues of psychostimulants. PMID:20933596

Suppressing effect of saikosaponin A, an active ingredient of Bupleurum falcatum, on chocolate self-administration and reinstatement of chocolate seeking in rats.

PubMed

Lorrai, Irene; Maccioni, Paola; Carai, Mauro A M; Capra, Alessandro; Castelli, M Paola; Riva, Antonella; Morazzoni, Paolo; Gessa, Gian Luigi; Colombo, Giancarlo

2017-01-18

Recent lines of experimental evidence have indicated that saikosaponin A (SSA) - a bioactive ingredient of the medicinal plant, Bupleurum falcatum L. - suppressed alcohol, morphine, and cocaine self-administration in rats. The present paper was designed to assess whether the protective properties of SSA on addiction-related behaviors generalize to a hyperpalatable food such as a chocolate-flavored beverage (CFB). To this end, rats were initially trained to lever-respond for CFB [5% (w/v) Nesquik ® powder in water] under fixed ratio (FR) 10 (FR10) schedule of reinforcement. Once lever-responding reached stable levels, rats were treated acutely with two different dose ranges of SSA (0, 0.25, 0.5, and 1mg/kg; 0, 1, 2.5, and 5mg/kg; i.p.) and exposed to the FR10 and progressive ratio (PR) schedules of reinforcement in four independent experiments. The effect of acutely administered SSA (0, 0.25, 0.5, and 1mg/kg; i.p.) on cue-induced reinstatement of seeking behavior for CFB was also assessed. Under the FR and PR schedules of reinforcement, treatment with SSA diminished lever-responding for CFB, amount of self-administered CFB, and breakpoint for CFB. All variables were virtually completely suppressed after treatment with 5mg/kg SSA. Treatment with SSA also suppressed reinstatement of CFB-seeking behavior. No dose of SSA altered rat motor-performance, evaluated exposing all rats to an inverted screen test immediately after the self-administration session. These results demonstrate that acute treatment with SSA potently suppressed several addictive-like behaviors motivated by highly hedonic nourishment. These data extend to a highly rewarding natural stimulus the anti-addictive properties of SSA recently disclosed in rats self-administering alcohol, morphine, and cocaine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The relationship between involuntary pelvic floor muscle activity, muscle awareness and experienced threat in women with and without vaginismus.

PubMed

van der Velde, J; Everaerd, W

2001-04-01

This study assessed the relationship between involuntary pelvic floor muscle activity, muscle awareness and experienced threat in women with and without vaginismus. Information about this relationship may help understand the mechanism of vaginismus. Twenty-two women with vaginismus and seven control women participated in the study. Women were exposed to four emotion-inducing film excerpts. Vaginal electromyography was recorded. Experienced threat was continuously monitored with the use of a lever. Women responded with increased pelvic floor muscle activity to the threatening and sexually-threatening film excerpt. No changes occurred during the neutral and erotic excerpt. The subjective experienced threat as indicated with the lever showed the same response pattern. However, awareness of changes in muscle activity showed a slightly different pattern. Individual data were inspected. In general, agreement was found between recorded changes in muscle activity and experienced threat. The results of the erotic excerpt showed that awareness of changes in muscle activity is not only determined by information from the pelvic floor muscles, but also by other factors like situational information and the expectations of the women. The data support the idea of a general defense reaction as a mechanism of involuntary pelvic floor muscle activity.

Differential Acquisition of Lever Pressing in Inbred and Outbred Mice: Comparison of One-Lever and Two-Lever Procedures and Correlation with Differences in Locomotor Activity

PubMed Central

McKerchar, Todd L; Zarcone, Troy J; Fowler, Stephen C

2005-01-01

Recent progress in mouse genetics has led to an increased interest in developing procedures for assessing mouse behavior, but relatively few of the behavioral procedures developed involve positively reinforced operant behavior. When operant methods are used, nose poking, not lever pressing, is the target response. In the current study differential acquisition of milk-reinforced lever pressing was observed in five inbred strains (C57BL/6J, DBA/2J, 129X1/SvJ, C3H/HeJ, and BALB/cJ) and one outbred stock (CD-1) of mice. Regardless of whether one or two levers (an “operative” and “inoperative” lever) were in the operant chamber, a concomitant variable-time fixed-ratio schedule of milk reinforcement established lever pressing in the majority of mice within two 120-min sessions. Substantial differences in lever pressing were observed across mice and between procedures. Adding an inoperative lever retarded acquisition in C57BL/6J, DBA/2J, 129X1/SvJ, and C3H/HeJ mice, but not in CD-1 and BALB/cJ mice. Locomotor activity was positively correlated with number of lever presses in both procedures. Analyses of durations of the subcomponents (e.g., time to move from hopper to lever) of operant behavior revealed further differences among the six types of mice. Together, the data suggest that appetitively reinforced lever pressing can be acquired rapidly in mice and that a combination of procedural, behavioral, and genetic variables contributes to this acquisition. PMID:16596969

Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, P.K.; Wang, G.; Thanos, P.K.

Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and amore » progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.« less

Parametric changes in response equilibrium during an intra-cranial self stimulation (ICSS) task: can reward value be assessed independently of absolute threshold?

PubMed

Easterling, K W; Holtzman, S G

1997-01-01

Traditional ICSS methodologies have attempted to evaluate changes in the rewarding value of brain stimulation by assessing the lowest value of the stimulation that will support responding. However, orderly changes in suprathreshold indicants of hedonic magnitude such as titration point have been shown. In the present experiments, rats were trained to respond on two ICSS autotitration schedules in which every response on one lever produced stimulation of the medial forebrain bundle, and every Xth response decreased either the stimulation current or the stimulation frequency. At any time, a response on a second "reset" lever restored the stimulation current or frequency available on the stimulation lever to its starting level and operationally defined changes in "reward value". In order to study this titration point measure, two response requirements (responses/stepdown; step size) and two stimulation parameters (initial stimulation level; train duration) were systematically varied. Under both current and frequency titration schedules, data indicated that response rate and titration point remained stable over repeated trials and multiple testing days--parameters being constant. Across all conditions, compared to the frequency titration schedule, subjects responding under the current titration schedule showed significantly higher titration points and lower rates of responding. Indicating the independence of rate and titration point data, parametric manipulations did not affect titration point and rate data concurrently. Results support the conclusion that titration point is a relative measure of "reward value" that is generally independent of response rate, but that is affected by manipulations that alter the amount of stimulation available between "resets". Additional work is needed in order to determine the relationship between the magnitude of stimulation needed to maintain minimal responding and that needed to maintain response equilibrium in an autotitration task.

Ethanol induces impulsive-like responding in a delay-of-reward operant choice procedure: impulsivity predicts autoshaping.

PubMed

Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D

1998-10-01

Autoshaping conditioned responses (CRs) are reflexive and targeted motor responses expressed as a result of experience with reward. To evaluate the hypothesis that autoshaping may be a form of impulsive responding, within-subjects correlations between performance on autoshaping and impulsivity tasks were assessed in 15 Long-Evans hooded rats. Autoshaping procedures [insertion of retractable lever conditioned stimulus (CS) followed by the response-independent delivery of food (US)] were followed by testing for impulsive-like responding in a two-choice lever-press operant delay-of-reward procedure (immediate small food reward versus delayed large food reward). Delay-of-reward functions revealed two distinct subject populations. Subjects in the Sensitive group (n=7) were more impulsive-like, increasing immediate reward choices at longer delays for large reward, while those in the Insensitive group (n=8) responded predominantly on only one lever. During the prior autoshaping phase, the Sensitive group had performed more autoshaping CRs, and correlations revealed that impulsive subjects acquired the autoshaping CR in fewer trials. In the Sensitive group, acute injections of ethanol (0, 0.25, 0.50, 1.00, 1.50 g/kg) given immediately before delay-of-reward sessions yielded an inverted U-shaped dose-response curve with increased impulsivity induced by the 0.25, 0.50, and 1.00 g/kg doses of ethanol, while choice strategy of the Insensitive group was not influenced by ethanol dose. Ethanol induced impulsive-like responding only in rats that were flexible in their response strategy (Sensitive group), and this group also performed more autoshaping CRs. Data support the hypothesis that autoshaping and impulsivity are linked.

75 FR 48921 - Administrative Guidance for Multistate Extension Activities and Integrated Research and Extension...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-12

.... Section 105 of AREERA amended the Smith-Lever Act to require that a specified amount of agricultural... Hatch Act and Smith-Lever Act to require that a specified amount of agricultural research and extension... Smith- Lever Act funds on multistate extension activities and 25 percent on integrated research and...

The effects of amphetamine sensitization on conditioned inhibition during a Pavlovian-instrumental transfer task in rats.

PubMed

Shiflett, Michael W; Riccie, Meaghan; DiMatteo, RoseMarie

2013-11-01

Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Adult male Long-Evans rats were given conditioned inhibition (A+/AX-) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to D-amphetamine (2 mg/kg daily injections for 7 days) or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50 % of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever pressing on BX trials and reduced lever pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food cup approach. Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor by enhancing the excitation of conditioned stimuli and reducing the inhibition of conditioned inhibitors.

Effects of an ethanol-paired CS on responding for ethanol and food: Comparisons with a stimulus in a Truly-Random-Control group and to a food-paired CS on responding for food.

PubMed

Lamb, R J; Ginsburg, Brett C; Schindler, Charles W

2016-12-01

Motivational increases due to exposure to alcohol-paired Conditioned Stimuli (CS) are central to some accounts of alcoholism. However, few studies isolate a stimulus's function as a CS from its other potential functions. Pavlovian-Instrumental-Transfer (PIT) procedures isolate a stimulus's function as a CS from its other functions. Though there are several relevant studies using PIT, knowledge gaps exist. Particularly, it is not clear that an alcohol-paired CS will increase alcohol seeking compared to the same stimulus in a Truly-Random-Control group, nor whether such increases are specific to alcohol seeking. To address these knowledge gaps in Experiment 1, rats responded for ethanol (0.1 ml 8% w/v) under an RI 30-sec schedule, then the lever was removed and half the rats had ethanol delivered during occasional 120-sec light presentations, while the remainder had ethanol and the light presented under independent RT schedules. Later the lever was returned and the light was presented during responding in extinction (PIT test). Following this test, levers were again removed and the light was presented without ethanol (light extinction), following again by a PIT test. Responding in the two groups during light presentations did not differ in either PIT test. Experiment 2 repeated Experiment 1 using food instead of ethanol. In Experiment 2, responding during light presentations increased in the paired group. In Experiment 3, rats were trained on a concurrent FR schedule of food and ethanol delivery. Ethanol was delivered following 5 responses and the response requirement for food adjusted so that similar numbers of food and ethanol deliveries were obtained. Subsequently, rats underwent conditioning, control and testing procedures identical to those in Experiment 1. In Experiment 3, the ethanol-paired CS increased ethanol-responding, but not food-responding. These results are most easily interpreted as changes in responding resulting from CS-elicited behavior rather than motivational changes. This interpretation is more compatible with some descriptions of the role of an alcohol-paired CS in alcoholism than others. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison between male and female rats in a model of self-administration of a chocolate-flavored beverage: Behavioral and neurochemical studies.

PubMed

Contini, Andrea; Sanna, Fabrizio; Maccioni, Paola; Colombo, Giancarlo; Argiolas, Antonio

2018-05-15

The existence of sex differences was studied in a rat model of operant self-administration of a chocolate-flavored beverage (CFB), which possesses strong reinforcing properties and is avidly consumed by rats. Whether these differences occurred concomitantly to changes in extracellular dopamine in the dialysate obtained from the nucleus accumbens, was assessed by intracerebral microdialysis. Male, ovariectomized and intact female rats showed similar self-administration profiles, with minor differences in both acquisition and maintenance phases. Intact females self-administered larger amounts of CFB, when expressed per body weight, than males and ovariectomized females, in spite of similar values of lever-responding, latency to the first lever-response and consumption efficiency (a measure of rat's licking effectiveness) in males, ovariectomized and intact females and no difference in breakpoint value and number of lever-responses emerged when males, ovariectomized and intact females were exposed to a progressive ratio schedule of reinforcement. Intracerebral microdialysis revealed a slight but significant increase in dopamine activity in the shell of the nucleus accumbens of male rats when compared to intact female rats during CFB self-administration. The above differences may be caused by the hormonal (mainly estradiol) fluctuations that occur during the estrus cycle in intact females. Accordingly, in intact females CFB self-administration and dopamine activity were found to fluctuate across the estrus cycle, with lower parameters of CFB self-administration and lower dopamine activity in the Proestrus and Estrus phases vs. the Metestrus and Diestrus phases of the cycle. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute ethanol effects on neural encoding of reward size and delay in the nucleus accumbens

PubMed Central

Gutman, Andrea L.

2016-01-01

Acute ethanol administration can cause impulsivity, resulting in increased preference for immediately available rewards over delayed but more valuable alternatives. The manner in which reward size and delay are represented in neural firing is not fully understood, and very little is known about ethanol effects on this encoding. To address this issue, we used in vivo electrophysiology to characterize neural firing in the core of the nucleus accumbens (NAcc) in rats responding for rewards that varied in size or delay after vehicle or ethanol administration. The NAcc is a central element in the circuit that governs decision-making and importantly, promotes choice of delayed rewards. We found that NAcc firing in response to reward-predictive cues encoded anticipated reward value after vehicle administration, but ethanol administration disrupted this encoding, resulting in a loss of discrimination between immediate and delayed rewards in cue-evoked neural responses. In addition, NAcc firing occurring at the time of the operant response (lever pressing) was inversely correlated with behavioral response latency, such that increased firing rates were associated with decreased latencies to lever press. Ethanol administration selectively attenuated this lever press-evoked firing when delayed but not immediate rewards were expected. These effects on neural firing were accompanied by increased behavioral latencies to respond for delayed rewards. Our results suggest that ethanol effects on NAcc cue- and lever press-evoked encoding may contribute to ethanol-induced impulsivity. PMID:27169507

The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay

PubMed Central

Strickland, Justin C.; Feinstein, Max A.; Lacy, Ryan T.; Smith, Mark A.

2016-01-01

Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-second delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures. PMID:26964905

Pavlovian conditioning with ethanol: sign-tracking (autoshaping), conditioned incentive, and ethanol self-administration.

PubMed

Krank, Marvin D

2003-10-01

Conditioned incentive theories of addictive behavior propose that cues signaling a drug's reinforcing effects activate a central motivational state. Incentive motivation enhances drug-taking and drug-seeking behavior. We investigated the behavioral response to cues associated with ethanol and their interaction with operant self-administration of ethanol. In two experiments, rats received operant training to press a lever for a sweetened ethanol solution. After operant training, the animals were given Pavlovian pairings of a brief and localized cue light with the sweetened ethanol solution (no lever present). Lever pressing for ethanol was then re-established, and the behavioral effects of the cue light were tested during an ethanol self-administration session. The conditioned responses resulting from pairing cue lights with the opportunity to ingest ethanol had three main effects: (1) induction of operant behavior reinforced by ethanol, (2) stimulation of ethanol-seeking behavior (magazine entries), and (3) signal-directed behavior (i.e., autoshaping, or sign-tracking). Signal-directed behavior interacted with the other two effects in a manner predicted by the location of the cue light. These conditioned responses interact with operant responding for ethanol reinforcement. These findings demonstrate the importance of Pavlovian conditioning effects on ethanol self-administration and are consistent with conditioned incentive theories of addictive behavior.

Long-lasting resistance to extinction of response reinstatement induced by ethanol-related stimuli: role of genetic ethanol preference.

PubMed

Ciccocioppo, R; Angeletti, S; Weiss, F

2001-10-01

The conditioning of ethanol's reinforcing effects with specific environmental stimuli is thought to be a critical factor in long-lasting relapse risk associated with alcoholism. To study the significance of such learning factors in the addictive potential of ethanol, this experiment was designed (1) to characterize the effects of stimuli associated with alcohol availability on the reinstatement of responding at a previously ethanol-paired lever in rats with genetically determined ethanol preference versus nonpreference and (2) to examine the persistence of the motivating effects of these stimuli over time. Male alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were trained to operantly self-administer ethanol (10% w/v) or water on a fixed-ratio 1 schedule in a 30-min daily session. Ethanol and water sessions were scheduled in random sequence across training days. Ethanol availability was signaled by an olfactory discriminative stimulus (banana extract, S+), and each lever press was paired with brief presentation of the conditioning chamber's house light (CS+). The discriminative stimulus signaling water availability (i.e., nonreward) consisted of anise odor (S-), and lever-responses during water sessions were paired with a brief white noise generation (CS-). The rats then were placed on extinction conditions during which ethanol and water, as well as the corresponding stimuli, were withheld. The effects of noncontingent exposure to the S+ versus S- paired with response-contingent presentation of the CS+ versus CS- on responding at the previously active lever were then determined in 30-min reinstatement sessions. To study the resistance to extinction of the effects of the ethanol-associated stimuli, additional tests were conducted at 3-day intervals for a total of 50 days. The number of ethanol-reinforced responses during self-administration training was significantly greater in P than in NP rats (p < 0.01). After extinction, a significant recovery of responding was observed in both groups of rats under the stimulus conditions associated with ethanol (S+/CS+) but not those associated with water (S-/CS-). However, the response reinstatement was significantly greater in P than NP rats (p < 0.01). In addition, the results revealed a considerable resistance to extinction to the effects of the ethanol-associated stimuli. Throughout the 50-day test period, responding remained significantly above extinction levels in both P and NP rats (p < 0.01), but with an overall greater number of responses in P than NP rats (p < 0.05). The results support the hypothesis that conditioning factors contribute importantly to compulsive ethanol seeking and long-lasting vulnerability to relapse. In addition, the results suggest that genetic predisposition toward heightened ethanol intake extends to greater susceptibility to the motivating effects of ethanol-related environmental stimuli.

Recovery of Pavlovian sign-tracking (autoshaping) following the discontinuation of inter-trial interval food in rats.

PubMed

Kearns, David N; Weiss, Stanley J

2007-07-01

In pigeons, Pavlovian autoshaped keypecking produced by keylight-food pairings has been eliminated by introducing food during periods between CS presentations (i.e., during the inter-trial intervals). Keypecking eliminated in this manner reappears when the inter-trial USs are discontinued even though the CS is no longer paired with US. The present experiment investigated whether this recovery of responding produced by discontinuing unpaired inter-trial US presentations could be extended to another species, rats, within a Pavlovian sign-tracking paradigm. Rats were initially trained on a procedure where insertion of one retractable lever (CS(+)) was followed, response independently, with food, while insertion of another lever (CS(-)) was not paired with food. Rats quickly came to contact the CS(+) lever at high rates, but contacted the CS(-) lever infrequently. In the next phase, CS(+) was no longer followed by food. Explicitly unpaired food was presented only during the inter-trial intervals when both levers were absent. This treatment essentially eliminated the sign-tracking response. In the final phase, the unpaired inter-trial food presentations were discontinued while both CSs continued to be presented without food. This produced a significant recovery of the sign-tracking elicited by the CS(+) lever, extending the species generality of the Pavlovian resurgence phenomenon that has previously only been reported in pigeons, to rats.

Comparison of the effect of the GABAB receptor agonist, baclofen, and the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in three different lines of alcohol-preferring rats

PubMed Central

Maccioni, Paola; Zaru, Alessandro; Loi, Barbara; Lobina, Carla; Carai, Mauro A.M.; Gessa, Gian Luigi; Capra, Alessandro; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Hyytiä, Petri; Lumeng, Lawrence; Colombo, Giancarlo

2012-01-01

Background Administration of the GABAB receptor agonist, baclofen, and positive allosteric modulator (PAM), GS39783, has been repeatedly reported to suppress multiple alcohol-related behaviors, including operant oral alcohol self-administration, in rats. The present study was designed to compare the effect of baclofen and GS39783 on alcohol self-administration in three lines of selectively bred, alcohol-preferring rats: Indiana alcohol-preferring (P), Sardinian alcohol-preferring (sP), and Alko Alcohol (AA). Methods Rats of each line were initially trained to respond on a lever, on a fixed ratio (FR) 4 (FR4) schedule of reinforcement, to orally self-administer alcohol (15%, v/v) in daily 30-min sessions. Once responding reached stable levels, rats were exposed to a sequence of experiments testing baclofen (0, 1, 1.7, and 3 mg/kg; i.p.) and GS39783 (0, 25, 50, and 100 mg/kg; i.g.) on FR4 and progressive ratio (PR) schedules of reinforcement. Finally, to assess the specificity of baclofen and GS39783 action, rats were slightly food-deprived and trained to lever-respond for food pellets. Results The rank of order of the reinforcing and motivational properties of alcohol was: P>sP>AA rats. Under both FR and PR schedules of reinforcement, the rank of order of potency and efficacy of baclofen and GS39783 in suppressing alcohol self-administration was: P>sP>AA rats. Only the highest dose of baclofen reduced lever-responding for food pellets; this effect was common to all three rat lines. Conversely, no dose of GS39783 altered lever-responding for food in any rat line. Conclusions These results suggest that: (a) the strength of the reinforcing and motivational properties of alcohol differ among P, sP, and AA rats; (b) the reinforcing and motivational properties of alcohol in P, sP, and AA rats are differentially sensitive to treatment with baclofen and GS39783; (c) the heterogeneity in sensitivity to baclofen and GS39783 of alcohol self-administration in P, sP, and AA rats may resemble the differential effectiveness of pharmacotherapies among the different typologies of human alcoholics; (d) the GABAB receptor is part of the neural substrate mediating the reinforcing and motivational properties of alcohol. PMID:22486245

Effects of contingent and noncontingent nicotine on lever pressing for liquids and consumption in water-deprived rats.

PubMed

Frenk, Hanan; Martin, Jeffrey; Vitouchanskaia, Cristina; Dar, Reuven; Shalev, Uri

2017-01-05

Nicotine has been proposed to be a primary reinforcer and a reinforcement enhancer. To date, no studies have examined whether nicotine enhances consummatory behaviors or only operant responding (appetitive behaviors). Experiments were designed to test whether contingent and noncontingent nicotine enhance lever pressing for and consumption of fluids in water-deprived rats. Animals were water-deprived throughout all experiments. They were trained to press two levers under a variable interval (VI-20, 1-35s). Their lever pressing and water consumption were measured after noncontingent subcutaneous (s.c.) injection of nicotine (1mg/kg), and in 3 choice conditions (water and quinine solution (18µg/ml); water and nicotine (32µg/ml) solution; quinine (18µg/ml) and nicotine (32µg/ml) solutions) where nicotine was thus delivered contingently upon lever pressing. The effects of nicotine (1mg/kg; s.c.) on the consumption of water in a time-limited free access (1h) paradigm were assessed. Nicotine significantly increased lever pressing and the number of earned reinforcements on both levers in the two choice conditions and when administered s.c. compared to all groups that did not receive nicotine. However, under no condition did animals consume more fluids than baseline. Under the time-limited free access condition nicotine reduced water consumption. Although our findings do not support a reinforcing effect for nicotine, they are consistent with the incentive-amplification hypothesis. Its relevance for human smoking is yet unclear. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of the basolateral amygdala in punishment

PubMed Central

Jean-Richard-Dit-Bressel, Philip

2015-01-01

Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects punishment task to assess the role of the BLA in the acquisition and expression of punishment as well as aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of GABA agonists baclofen and muscimol (BM) into the BLA significantly impaired the acquisition of this suppression. BLA inactivations using BM also reduced the expression of well-trained punishment. There was anatomical segregation within the BLA so that caudal, not rostral, BLA was implicated in punishment. However, when presented with punished and unpunished levers simultaneously in a choice test without deliveries of shock punisher, rats expressed a preference for unpunished over the punished lever and BLA inactivations had no effect on this preference. Taken together, these findings indicate that the BLA is important for both the acquisition and expression of punishment but not for aversive choice. This role appears to be linked to neurons in the caudal BLA, rather than rostral BLA, although the circuitry that contributes to this functional segregation is currently unknown, and is most parsimoniously interpreted as a role for caudal BLA in determining the aversive value of the shock punisher. PMID:25593299

Dopamine efflux in the nucleus accumbens during within-session extinction, outcome-dependent, and habit-based instrumental responding for food reward.

PubMed

Ahn, Soyon; Phillips, Anthony G

2007-04-01

Dopamine (DA) activity in the nucleus accumbens (NAc) is related to the general motivational effects of rewarding stimuli. Dickinson and colleagues have shown that initial acquisition of instrumental responding reflects action-outcome relationships based on instrumental incentive learning, which establishes the value of an outcome. Given that the sensitivity of responding to outcome devaluation is not affected by NAc lesions, it is unlikely that incentive learning during the action-outcome phase is mediated by DA activity in the NAc. DA efflux in the NAc after limited and extended training was compared on the assumption that comparable changes would be observed during both action-outcome- and habit-based phases of instrumental responding for food. This study also tested the hypothesis that increase in NAc DA activity is correlated with instrumental responding during extinction maintained by a conditioned stimulus paired with food. Rats were trained to lever press for food (random-interval 30 s schedule). On the 5th and 16th day of training, microdialysis samples were collected from the NAc or mediodorsal striatum (a control site for generalized activity) during instrumental responding in extinction and then for food reward, and analyzed for DA content using high performance liquid chromatography. Increase in DA efflux in the NAc accompanied responding for food pellets on both days 5 and 16, with the magnitude of increase significantly enhanced on day 16. DA efflux was also significantly elevated during responding in extinction only on day 16. These results support a role for NAc DA activity in Pavlovian, but not instrumental, incentive learning.

Access to a running wheel inhibits the acquisition of cocaine self-administration.

PubMed

Smith, Mark A; Pitts, Elizabeth G

2011-12-01

Physical activity decreases cocaine self-administration in laboratory animals and is associated with positive outcomes in substance abuse treatment programs; however, less is known about its efficacy in preventing the establishment of regular patterns of substance use in drug-naive individuals. The purpose of the present study was to examine the effects of access to a running wheel on the acquisition of cocaine self-administration in experimentally naive rats. Male, Long-Evans rats were obtained at weaning and assigned to sedentary (no wheel) or exercising (access to wheel) conditions immediately upon arrival. After six weeks, rats were surgically implanted with intravenous catheters and placed in operant conditioning chambers for 2 h/day for 15 consecutive days. Each session began with a noncontingent priming infusion of cocaine, followed by a free-operant period in which each response on the active lever produced an infusion of cocaine on a fixed ratio (FR1) schedule of reinforcement. For days 1-5, responding was reinforced with 0.25 mg/kg/infusion cocaine; for days 6-15, responding was reinforced with 0.75 mg/kg/infusion cocaine. In addition, all rats were calorically restricted during days 11-15 to 85% to 95% of their free-feeding body weight. Compared to sedentary rats, exercising rats acquired cocaine self-administration at a significantly slower rate and emitted significantly fewer active lever presses during the 15 days of behavioral testing. These data indicate that access to a running wheel inhibits the acquisition of cocaine self-administration, and that physical activity may be an effective intervention in substance abuse prevention programs. Copyright © 2011 Elsevier Inc. All rights reserved.

Repeated Cocaine Experience Facilitates Sucrose-Reinforced Operant Responding in Enriched and Isolated Rats

ERIC Educational Resources Information Center

Klein, Emily D.; Gehrke, Brenda J.; Green, Thomas A.; Zentall, Thomas R.; Bardo, Michael T.

2007-01-01

The purpose of the present experiment was to determine whether repeated cocaine exposure differentially affects sucrose-reinforced operant responding in rats raised in an enriched condition (EC) or an isolated condition (IC). Specifically, the performance of EC and IC rats pressing a lever for sucrose under a high fixed-ratio schedule (FR 30)…

Differential Acquisition of Lever Pressing in Inbred and Outbred Mice: Comparison of One-Lever and Two-Lever Procedures and Correlation with Differences in Locomotor Activity

ERIC Educational Resources Information Center

McKerchar, Todd L.; Zarcone, Troy J.; Fowler, Stephen C.

2005-01-01

Recent progress in mouse genetics has led to an increased interest in developing procedures for assessing mouse behavior, but relatively few of the behavioral procedures developed involve positively reinforced operant behavior. When operant methods are used, nose poking, not lever pressing, is the target response. In the current study differential…

Effects of sucrose concentration and water deprivation on Pavlovian conditioning and responding for conditioned reinforcement.

PubMed

Tabbara, Rayane I; Maddux, Jean-Marie N; Beharry, Priscilla F; Iannuzzi, Jessica; Chaudhri, Nadia

2016-04-01

An appetitive Pavlovian conditioned stimulus (CS) can predict an unconditioned stimulus (US) and acquire incentive salience. We tested the hypothesis that US intensity and motivational state of the subject would influence Pavlovian learning and impact the attribution of incentive salience to an appetitive Pavlovian CS. To this end, we examined the effects of sucrose concentration and water deprivation on the acquisition of Pavlovian conditioning and responding for a conditioned reinforcer. Male Long-Evans rats (Harlan; 220-240 g) receiving 3% (3S) or 20% (20S) sucrose were either non-water deprived or given water for 1 hr per day. During Pavlovian conditioning sessions, half the rats in each concentration and deprivation condition received a 10-s CS paired with 0.2 ml of sucrose (16 trials/session; 3.2 ml/session). The remainder received unpaired CS and US presentations. Entries into a port where sucrose was delivered were recorded. Next, responding for conditioned reinforcement was tested, wherein pressing an active lever produced the CS and pressing an inactive lever had no consequences. CS-elicited port entries increased, and latency to the first CS-elicited port entry decreased across sessions in paired groups. Water deprivation augmented these effects, whereas sucrose concentration had no significant impact on behavior. Responding for conditioned reinforcement was observed in the 20S water-deprived, paired group. Thus, water deprivation can facilitate the acquisition of Pavlovian conditioning, potentially by enhancing motivational state, and a high-intensity US and a high motivational state can interact to heighten the attribution of incentive salience to an appetitive Pavlovian CS. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The effects of amphetamine sensitization on conditioned inhibition during a Pavlovian-instrumental transfer task in rats

PubMed Central

Shiflett, Michael W.; Riccie, Meaghan; DiMatteo, RoseMarie

2013-01-01

Rationale Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. Objectives We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Methods Adult male Long Evans rats were given conditioned inhibition (A+/AX−) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to d-amphetamine (2 mg/kg daily injections for seven days), or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). Results During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50% of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever-pressing on BX trials and reduced lever-pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever-pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food-cup approach. Conclusions Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor, by enhancing excitation of conditioned stimuli and reducing inhibition of conditioned inhibitors. PMID:23715640

Using drug combinations to assess potential contributions of non-GABAA receptors in the discriminative stimulus effects of the neuroactive steroid pregnanolone in rats.

PubMed

Eppolito, Amy K; Kodeih, Hanna R; Gerak, Lisa R

2014-10-01

Neuroactive steroids are increasingly implicated in the development of depression and anxiety and have been suggested as possible treatments for these disorders. While neuroactive steroids, such as pregnanolone, act primarily at γ-aminobutyric acidA (GABAA) receptors, other mechanisms might contribute to their behavioral effects and could increase their clinical effectiveness, as compared with drugs acting exclusively at GABAA receptors (e.g., benzodiazepines). The current study examined the role of non-GABAA receptors, including N-methyl-d-aspartate (NMDA) and serotonin3 (5-HT3) receptors, in the discriminative stimulus effects of pregnanolone. Separate groups of rats discriminated either 3.2mg/kg pregnanolone from vehicle or 0.32mg/kg of the benzodiazepine midazolam from vehicle while responding under a fixed-ratio 10 schedule for food pellets. When administered alone in both groups, pregnanolone and midazolam produced ≥80% drug-lever responding, the NMDA receptor antagonists dizocilpine and phencyclidine produced ≥60 and ≥30% drug-lever responding, respectively, and the 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (CPBG) and morphine produced <20% drug-lever responding up to doses that markedly decreased response rates. When studied together, neither dizocilpine, phencyclidine, CPBG nor morphine significantly altered the midazolam dose-effect curve in either group. Given that CPBG is without effect, it is unlikely that 5-HT3 receptors contribute substantially to the discriminative stimulus effects of pregnanolone. Similarities across groups in effects of dizocilpine and phencyclidine suggest that NMDA receptors do not differentially contribute to the effects of pregnanolone. Thus, NMDA and 5-HT3 receptors are not involved in the discriminative stimulus effects of pregnanolone. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of baclofen and raclopride on reinstatement of cocaine self-administration in the rat.

PubMed

Froger-Colléaux, Christelle; Castagné, Vincent

2016-04-15

At present there is no satisfactory treatment against relapse of drug-seeking behavior. Relapse can be modeled in laboratory animals using reinstatement procedures, whereby previously extinguished self-administration for a drug is reinstated by different factors, such as exposure to cues or drug priming. It is thought that activation of gamma-aminobutyric acid (GABA) B receptor complexes could represent a promising approach to pharmacotherapy for diminishing relapse potential with drugs possessing reinforcing properties. The effects of baclofen (a prototypic GABAB receptor agonist) on cue-induced cocaine reinstatement were evaluated in the rat with or without a priming injection of cocaine. The effects of raclopride (an antagonist of dopamine D2 receptors) were also evaluated. Cue-induced reinstatement under vehicle resulted in a significant increase in the number of presses on the active lever, as compared with extinction lever responding. This effect was accentuated in rats receiving a priming injection of cocaine (cocaine-plus-cue-induced reinstatement). Baclofen, at doses without effects on food-motivated operant behavior (2.5 and 5mg/kg i.p.), dose-dependently decreased the number of active lever presses during cue-induced reinstatement. Baclofen had slightly weaker effects on cocaine-plus-cue-induced reinstatement. Raclopride (0.08 and 0.15 mg/kg s.c.) had similar effects against cue-induced reinstatement although it failed to inhibit cocaine-plus-cue-induced reinstatement at the lower dose. Baclofen dose-dependently and selectively decreased reinstatement of cocaine self-administration. The data obtained provide support for the potential anti-craving efficacy of baclofen in the treatment of cocaine drug-seeking. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Post-Session Wheel Running on Within-Session Changes in Operant Responding

ERIC Educational Resources Information Center

Aoyama, Kenjiro

2007-01-01

This study tested the effects of post-session wheel running on within-session changes in operant responding. Lever-pressing by six rats was reinforced by a food pellet under a continuous reinforcement (CRF) schedule in 30-min sessions. Two different flavored food pellets were used as reinforcers. In the wheel conditions, 30-min operant-sessions…

The role of the basolateral amygdala in punishment.

PubMed

Jean-Richard-Dit-Bressel, Philip; McNally, Gavan P

2015-02-01

Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects punishment task to assess the role of the BLA in the acquisition and expression of punishment as well as aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of GABA agonists baclofen and muscimol (BM) into the BLA significantly impaired the acquisition of this suppression. BLA inactivations using BM also reduced the expression of well-trained punishment. There was anatomical segregation within the BLA so that caudal, not rostral, BLA was implicated in punishment. However, when presented with punished and unpunished levers simultaneously in a choice test without deliveries of shock punisher, rats expressed a preference for unpunished over the punished lever and BLA inactivations had no effect on this preference. Taken together, these findings indicate that the BLA is important for both the acquisition and expression of punishment but not for aversive choice. This role appears to be linked to neurons in the caudal BLA, rather than rostral BLA, although the circuitry that contributes to this functional segregation is currently unknown, and is most parsimoniously interpreted as a role for caudal BLA in determining the aversive value of the shock punisher. © 2015 Jean-Richard-Dit-Bressel and McNally; Published by Cold Spring Harbor Laboratory Press.

The effects of physical activity on impulsive choice: Influence of sensitivity to reinforcement amount and delay.

PubMed

Strickland, Justin C; Feinstein, Max A; Lacy, Ryan T; Smith, Mark A

2016-05-01

Impulsive choice is a diagnostic feature and/or complicating factor for several psychological disorders and may be examined in the laboratory using delay-discounting procedures. Recent investigators have proposed using quantitative measures of analysis to examine the behavioral processes contributing to impulsive choice. The purpose of this study was to examine the effects of physical activity (i.e., wheel running) on impulsive choice in a single-response, discrete-trial procedure using two quantitative methods of analysis. To this end, rats were assigned to physical activity or sedentary groups and trained to respond in a delay-discounting procedure. In this procedure, one lever always produced one food pellet immediately, whereas a second lever produced three food pellets after a 0, 10, 20, 40, or 80-s delay. Estimates of sensitivity to reinforcement amount and sensitivity to reinforcement delay were determined using (1) a simple linear analysis and (2) an analysis of logarithmically transformed response ratios. Both analyses revealed that physical activity decreased sensitivity to reinforcement amount and sensitivity to reinforcement delay. These findings indicate that (1) physical activity has significant but functionally opposing effects on the behavioral processes that contribute to impulsive choice and (2) both quantitative methods of analysis are appropriate for use in single-response, discrete-trial procedures. Copyright © 2016 Elsevier B.V. All rights reserved.

Rats do not respond differently in the presence of stimuli signaling wheel-running reinforcers of different durations.

PubMed

Belke, Terry W

2007-05-01

Rats were exposed to a fixed interval 30 s schedule that produced opportunities to run of equal or unequal durations to assess the effect of differences in duration on responding. Each duration was signaled by a different stimulus. Wheel-running reinforcer duration pairs were 30 s 30 s, 50 s 10 s, and 55 s 5 s. An analysis of median postreinforcement pause duration and mean local lever-pressing rates broken down by previous reinforcer duration and duration of signaled upcoming reinforcer showed that postreinforcement pause duration was affected by the duration of the previous reinforcer but not by the stimulus signaling the duration of the upcoming reinforcer. Local lever-pressing rates were not affected by either previous or upcoming reinforcer duration. In general, the results are consistent with indifference between these durations obtained using a concurrent choice procedure.

What role does performance information play in securing improvement in healthcare? a conceptual framework for levers of change

PubMed Central

Levesque, Jean-Frederic; Sutherland, Kim

2017-01-01

Objective Across healthcare systems, there is consensus on the need for independent and impartial assessment of performance. There is less agreement about how measurement and reporting performance improves healthcare. This paper draws on academic theories to develop a conceptual framework—one that classifies in an integrated manner the ways in which change can be leveraged by healthcare performance information. Methods A synthesis of published frameworks. Results The framework identifies eight levers for change enabled by performance information, spanning internal and external drivers, and emergent and planned processes: (1) cognitive levers provide awareness and understanding; (2) mimetic levers inform about the performance of others to encourage emulation; (3) supportive levers provide facilitation, implementation tools or models of care to actively support change; (4) formative levers develop capabilities and skills through teaching, mentoring and feedback; (5) normative levers set performance against guidelines, standards, certification and accreditation processes; (6) coercive levers use policies, regulations incentives and disincentives to force change; (7) structural levers modify the physical environment or professional cultures and routines; (8) competitive levers attract patients or funders. Conclusion This framework highlights how performance measurement and reporting can contribute to eight different levers for change. It provides guidance into how to align performance measurement and reporting into quality improvement programme. PMID:28851769

R(+)-Baclofen, but Not S(-)-Baclofen, Alters Alcohol Self-Administration in Alcohol-Preferring Rats.

PubMed

Lorrai, Irene; Maccioni, Paola; Gessa, Gian Luigi; Colombo, Giancarlo

2016-01-01

Racemic baclofen [(±)-baclofen] has repeatedly been reported to suppress several -alcohol-motivated behaviors, including alcohol drinking and alcohol -self-administration, in rats and mice. Recent data suggested that baclofen may have bidirectional, stereospecific effects, with the more active enantiomer, R(+)-baclofen, suppressing alcohol intake and the less active enantiomer, S(-)-baclofen, stimulating alcohol intake in mice. The present study was designed to investigate whether this enantioselectivity of baclofen effects may also extend to the reinforcing properties of alcohol in rats. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were initially trained to lever respond on a fixed ratio 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested with vehicle, (±)-baclofen (3 mg/kg), R(+)-baclofen (0.75, 1.5, and 3 mg/kg), and S(-)-baclofen (6, 12, and 24 mg/kg) under the FR4 schedule of reinforcement. Treatment with 3 mg/kg (±)-baclofen reduced the number of lever responses for alcohol and estimated amount of self-administered alcohol by approximately 60% in comparison to vehicle treatment. R(+)-baclofen was approximately twice as active as (±)-baclofen: treatment with 1.5 mg/kg R(+)-baclofen decreased both variables to an extent similar to that of the decreasing effect of 3 mg/kg (±)-baclofen. Conversely, treatment with all doses of S(-)-baclofen failed to affect alcohol self administration. These results (a) confirm that non-sedative doses of (±)-baclofen effectively suppressed the reinforcing properties of alcohol in sP rats and (b) apparently do not extend to operant alcohol self-administration in sP rats the capability of S(-)-baclofen to stimulate alcohol drinking in mice.

Progesterone attenuates impulsive action in a Go/No-Go task for sucrose pellets in female and male rats

PubMed Central

Swalve, Natashia; Smethells, John R.; Carroll, Marilyn E.

2016-01-01

Impulsivity, or a tendency to act without anticipation of future consequences, is associated with drug abuse. Impulsivity is typically separated into two main measures, impulsive action and impulsive choice. Given the association of impulsivity and drug abuse, treatments that reduce impulsivity have been proposed as an effective method for countering drug addiction. Progesterone has emerged as a promising treatment, as it is associated with decreased addiction-related behaviors and impulsive action. The goal of the present study was to determine the effects of progesterone (PRO) on impulsive action for food: a Go/No-Go task. Female and male rats responded for sucrose pellets during a Go component when lever pressing was reinforced on a variable-interval 30-s schedule. During the alternate No-Go component, withholding a lever press was reinforced on a differential reinforcement of other (DRO) behavior 30-s schedule, where a lever press reset the DRO timer. Impulsive action was operationally defined as the inability to withhold a response during the No-Go component (i.e. the number of DRO resets). Once Go/No-Go behavior was stable, responding between rats treated with PRO (0.5 mg/kg) or vehicle was examined. Progesterone significantly decreased the total number of DRO resets in both males and females, but it did not affect VI responding for sucrose pellets. This suggests that PRO decreases motor impulsivity for sucrose pellets without affecting motivation for food. Thus, PRO may reduce motor impulsivity, a behavior underlying drug addiction. PMID:27497836

Responding for sucrose and wheel-running reinforcement: effect of body weight manipulation.

PubMed

Belke, Terry W

2004-02-27

As body weight increases, the excitatory strength of a stimulus signaling an opportunity to run should weaken to a greater degree than that of a stimulus signaling an opportunity to eat. To test this hypothesis, six male albino Wistar rats were placed in running wheels and exposed to a fixed interval 30-s schedule that produced either a drop of 15% sucrose solution or the opportunity to run for 15s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. The effect of varying body weight on responding maintained by these two reinforcers was investigated by systematically increasing and decreasing post-session food amounts. The initial body weight was 335 g. Body weights were increased to approximately 445 g and subsequently returned to 335 g. As body weight increased, overall and local lever-pressing rates decreased while post-reinforcement pauses lengthened. Analysis of post-reinforcement pauses and local lever-pressing rates in terms of transitions between successive reinforcers revealed that local response rates in the presence of stimuli signaling upcoming wheel and sucrose reinforcers were similarly affected. However, pausing in the presence of the stimulus signaling a wheel-running reinforcer lengthened to a greater extent than did pausing in the presence of the stimulus signaling sucrose. This result suggests that as body weight approaches ad-lib levels, the likelihood of initiation of responding to obtain an opportunity to run approaches zero and the animal "rejects" the opportunity to run in a manner similar to the rejection of less preferred food items in studies of food selectivity.

Behavioral Momentum Theory Fails to Account for the Effects of Reinforcement Rate on Resurgence

PubMed Central

Craig, Andrew R.; Shahan, Timothy A.

2017-01-01

The behavioral-momentum model of resurgence predicts reinforcer rates within a resurgence preparation should have three effects on target behavior. First, higher reinforcer rates in baseline (Phase 1) produce more persistent target behavior during extinction plus alternative reinforcement. Second, higher rate alternative reinforcement during Phase 2 generates greater disruption of target responding during extinction. Finally, higher rates of either reinforcement source should produce greater responding when alternative reinforcement is suspended in Phase 3. Recent empirical reports have produced mixed results in terms of these predictions. Thus, the present experiment further examined reinforcer-rate effects on persistence and resurgence. Rats pressed target levers for high-rate or low-rate variable-interval food during Phase 1. In Phase 2, target-lever pressing was extinguished, an alternative nose-poke became available, and nose-poking produced either high-rate variable-interval, low-rate variable-interval, or no (an extinction control) alternative reinforcement. Alternative reinforcement was suspended in Phase 3. For groups that received no alternative reinforcement, target-lever pressing was less persistent following high-rate than low-rate Phase-1 reinforcement. Target behavior was more persistent with low-rate alternative reinforcement than with high-rate alternative reinforcement or extinction alone. Finally, no differences in Phase-3 responding were observed for groups that received either high-rate or low-rate alternative reinforcement, and resurgence occurred only following high-rate alternative reinforcement. These findings are inconsistent with the momentum-based model of resurgence. We conclude this model mischaracterizes the effects of rein-forcer rates on persistence and resurgence of operant behavior. PMID:27193242

Deepened extinction following compound stimulus presentation: Noradrenergic modulation

PubMed Central

Janak, Patricia H.; Corbit, Laura H.

2011-01-01

Behavioral extinction is an active form of new learning involving the prediction of nonreward where reward has previously been present. The expression of extinction learning can be disrupted by the presentation of reward itself or reward-predictive stimuli (reinstatement) as well as the passage of time (spontaneous recovery) or contextual changes (renewal). The following experiments replicated the demonstration that presenting multiple previously rewarded stimuli in compound during extinction enhances extinction learning. To explore the pharmacological basis for this we next examined the effects of pharmacological treatments that either facilitated or blocked noradrenergic activity to test the hypothesis that increased noradrenergic activity at the time of extinction training would improve, whereas blockade of noradrenergic activity would impair the extinction of appetitive stimulus–reward memories. Different groups of rats were trained in a discriminative stimulus paradigm to lever-press for food reward. Once stable responding was achieved, responding was extinguished for 2 d. Prior to a third extinction session, rats received systemic administration of either saline, yohimbine (α2 antagonist), atomoxetine (norepinephrine reuptake inhibitor), or propranolol (β-receptor antagonist). Spontaneous recovery of responding to the stimuli was tested 4 wk later. Our results indicate that increasing noradrenergic activity during extinction augments extinction learning resulting in less recovery of responding at test. These results have important implications for models of relapse to drug seeking and the development of extinction-based therapies. PMID:21224211

The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs

PubMed Central

Randall, Patrick A.; Lee, Christie A.; Nunes, Eric J.; Yohn, Samantha E.; Nowak, Victoria; Khan, Bilal; Shah, Priya; Pandit, Saagar; Vemuri, V. Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E.; Correa, Merce; Salamone, John D.

2014-01-01

Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients. PMID:24937131

The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a progressive ratio/chow feeding choice task: reversal with antidepressant drugs.

PubMed

Randall, Patrick A; Lee, Christie A; Nunes, Eric J; Yohn, Samantha E; Nowak, Victoria; Khan, Bilal; Shah, Priya; Pandit, Saagar; Vemuri, V Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E; Correa, Merce; Salamone, John D

2014-01-01

Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients.

Cocaine Self-Administration in Male and Female Rats Perinatally Exposed to PCBs: Evaluating Drug Use in an Animal Model of Environmental Contaminant Exposure

PubMed Central

Miller, Mellessa M.; Meyer, Abby E.; Sprowles, Jenna L. N.; Sable, Helen J. K.

2017-01-01

Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants known to adversely impact human health. Ortho-substituted PCBs affect the nervous system, including the brain dopaminergic system. The reinforcing effects of psychostimulants are typically modulated via the dopaminergic system, so this study used a preclinical (i.e., rodent) model to evaluate whether developmental contaminant exposure altered intravenous self-administration (i.v. SA) for the psychostimulant cocaine. Long Evans rats were perinatally exposed to 6 or 3 mg/kg/day of PCBs throughout gestation and lactation and compared to non-exposed controls. Rats were trained to lever press for a food reinforcer in an operant chamber under a fixed-ratio 5 (FR5) schedule and later underwent jugular catheterization. Food reinforcers were switched for infusions of 250 μg of cocaine, but the response requirement to earn the reinforcer remained. Active lever presses and infusions were higher in males during response acquisition and maintenance. The same sex effect was observed during later sessions which evaluated responding for cocaine doses ranging from 31.25 – 500 μg. PCB-exposed males (not females) exhibited an increase in cocaine infusions (with a similar trend in active lever presses) during acquisition, but no PCB-related differences were observed during maintenance, examination of the cocaine dose-response relationship, or progressive ratio sessions. Overall, these results indicated perinatal PCB exposure enhanced early cocaine drug-seeking in this preclinical model of developmental contaminant exposure (particularly the males), but no differences were seen during later cocaine SA sessions. As such, additional questions regarding substance abuse proclivity may be warranted in epidemiological studies evaluating environmental contaminant exposures. PMID:28287790

What role does performance information play in securing improvement in healthcare? a conceptual framework for levers of change.

PubMed

Levesque, Jean-Frederic; Sutherland, Kim

2017-08-28

Across healthcare systems, there is consensus on the need for independent and impartial assessment of performance. There is less agreement about how measurement and reporting performance improves healthcare. This paper draws on academic theories to develop a conceptual framework-one that classifies in an integrated manner the ways in which change can be leveraged by healthcare performance information. A synthesis of published frameworks. The framework identifies eight levers for change enabled by performance information, spanning internal and external drivers, and emergent and planned processes: (1) cognitive levers provide awareness and understanding; (2) mimetic levers inform about the performance of others to encourage emulation; (3) supportive levers provide facilitation, implementation tools or models of care to actively support change; (4) formative levers develop capabilities and skills through teaching, mentoring and feedback; (5) normative levers set performance against guidelines, standards, certification and accreditation processes; (6) coercive levers use policies, regulations incentives and disincentives to force change; (7) structural levers modify the physical environment or professional cultures and routines; (8) competitive levers attract patients or funders. This framework highlights how performance measurement and reporting can contribute to eight different levers for change. It provides guidance into how to align performance measurement and reporting into quality improvement programme. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats.

PubMed

Dhaher, Ronnie; Toalston, Jamie E; Hauser, Sheketha R; Bell, Richard L; McKinzie, David L; McBride, William J; Rodd, Zachary A

2012-02-01

Research indicates opioid antagonists can reduce alcohol drinking in rodents. However, tests examining the effects of opioid antagonists on ethanol seeking and relapse behavior have been limited. The present study examined the effects of two opioid antagonists on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Adult P rats were self-trained in two-lever operant chambers to self-administer 15% (vol/vol) ethanol on a fixed-ratio 5 (FR5) versus water on a FR1 concurrent schedule of reinforcement in daily 1-h sessions. After 10 weeks, rats underwent extinction training, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without ethanol or water to measure responses on the ethanol and water levers for four sessions. After a subsequent 2 weeks in the home cage, without access to ethanol, rats were returned to the operant chambers with ethanol and water available. Effects of antagonists on maintenance responding were tested after several weeks of daily 1-h sessions. Naltrexone (NAL; 1-10mg/kg, subcutaneously [s.c.]; n=8/dose), LY255582 (LY; 0.03-1mg/kg, s.c.; n=8/dose), or vehicle were injected 30min before the first session (in the absence of ethanol), following 2 weeks in their home cages, and for four consecutive sessions of ethanol self-administration under maintenance and relapse conditions. Both NAL and LY reduced responses on the ethanol lever without any fluids present, and ethanol self-administration under relapse and on-going drinking conditions, with LY being more potent than NAL. Both NAL and LY were less effective in reducing responding in the absence of ethanol than in reducing ethanol self-administration. Overall, the results indicate that the opioid system is involved in mediating ethanol seeking, and ethanol self-administration under relapse and on-going alcohol drinking, but that different neurocircuits may underlie these behaviors. Published by Elsevier Inc.

Intravenous nicotine self-administration in rats: effects of mecamylamine, hexamethonium and naloxone.

PubMed

DeNoble, Victor J; Mele, Paul C

2006-03-01

The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 microg/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 microg/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.

Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: vulnerability to relapse to heroin-seeking in rats

PubMed Central

Zhou, Yan; Leri, Francesco; Cummins, Erin; Jeanne Kreek, Mary

2014-01-01

Individual vulnerability to stress-induced relapse during abstinence from chronic heroin exposure is a key feature of opiate addiction, with limited studies on this topic. Arginine vasopressin (AVP) and its V1b receptor, components of the brain stress responsive systems, play a role in heroin-seeking behavior triggered by foot shock (FS) stress in rats. In this study, we tested whether individual differences in the FS-induced heroin-seeking were associated with alterations of AVP and V1b, as well as other stress responsive systems, including pro-opiomelanocortin (POMC), orexin, plasma ACTH and corticosterone, as well as dopamine D2 receptor (D2) and plasma prolactin. Sprague-Dawley rats were subjected to 3-hour intravenous heroin self-administration (SA) and then tested in extinction, FS-induced and heroin priming-induced reinstatements. The rats that self-administered heroin were divided to high and low reinstatement responders induced by FS (H-RI; L-RI). Over SA sessions, both the H-RI and L-RI displayed similar active lever responding, heroin infusion and total heroin intake. Compared to the L-RI, however, the H-RI showed greater active lever responses during stress-induced reinstatement, with higher AVP mRNA levels in medial/basolateral amygdala and lower D2 mRNA levels in caudate putamen. However, heroin priming resulted in similar reinstatement in both groups and produced similarly low POMC and high orexin mRNA levels in hypothalamus. Our results indicate that: 1) enhanced amygdalar AVP and reduced striatal D2 expression may be related to individual vulnerability to stress-induced reinstatement of heroin- seeking; and 2) heroin abstinence-associated alterations of hypothalamic orexin and POMC expression may be involved in drug priming-induced heroin-seeking. PMID:25446223

α-Conotoxin MII-Sensitive Nicotinic Acetylcholine Receptors in the Nucleus Accumbens Shell Regulate Progressive Ratio Responding Maintained by Nicotine

PubMed Central

Brunzell, Darlene H; Boschen, Karen E; Hendrick, Elizabeth S; Beardsley, Patrick M; McIntosh, J Michael

2010-01-01

β2 subunit containing nicotinic acetylcholine receptors (β2*nAChRs; asterisk (*) denotes assembly with other subunits) are critical for nicotine self-administration and nicotine-associated dopamine (DA) release that supports nicotine reinforcement. The α6 subunit assembles with β2 on DA neurons where α6β2*nAChRs regulate nicotine-stimulated DA release at neuron terminals. Using local infusion of α-conotoxin MII (α-CTX MII), an antagonist with selectivity for α6β2*nAChRs, the purpose of these experiments was to determine if α6β2*nAChRs in the nucleus accumbens (NAc) shell are required for motivation to self-administer nicotine. Long-Evans rats lever-pressed for 0.03 mg/kg, i.v., nicotine accompanied by light+tone cues (NIC) or for light+tone cues unaccompanied by nicotine (CUEonly). Following extensive training, animals were tested under a progressive ratio (PR) schedule that required an increasing number of lever presses for each nicotine infusion and/or cue delivery. Immediately before each PR session, rats received microinfusions of α-CTX MII (0, 1, 5, or 10 pmol per side) into the NAc shell or the overlying anterior cingulate cortex. α-CTX MII dose dependently decreased break points and number of infusions earned by NIC rats following infusion into the NAc shell but not the anterior cingulate cortex. Concentrations of α-CTX MII that were capable of attenuating nicotine self-administration did not disrupt locomotor activity. There was no effect of infusion on lever pressing in CUEonly animals and NAc infusion α-CTX MII did not affect locomotor activity in an open field. These data suggest that α6β2*nAChRs in the NAc shell regulate motivational aspects of nicotine reinforcement but not nicotine-associated locomotor activation. PMID:19890263

Stimulus generalization, discrimination learning, and peak shift in horses.

PubMed Central

Dougherty, D M; Lewis, P

1991-01-01

Using horses, we investigated three aspects of the stimulus control of lever-pressing behavior: stimulus generalization, discrimination learning, and peak shift. Nine solid black circles, ranging in size from 0.5 in. to 4.5 in. (1.3 cm to 11.4 cm) served as stimuli. Each horse was shaped, using successive approximations, to press a rat lever with its lip in the presence of a positive stimulus, the 2.5-in. (6.4-cm) circle. Shaping proceeded quickly and was comparable to that of other laboratory organisms. After responding was maintained on a variable-interval 30-s schedule, stimulus generalization gradients were collected from 2 horses prior to discrimination training. During discrimination training, grain followed lever presses in the presence of a positive stimulus (a 2.5-in circle) and never followed lever presses in the presence of a negative stimulus (a 1.5-in. [3.8-cm] circle). Three horses met a criterion of zero responses to the negative stimulus in fewer than 15 sessions. Horses given stimulus generalization testing prior to discrimination training produced symmetrical gradients; horses given discrimination training prior to generalization testing produced asymmetrical gradients. The peak of these gradients shifted away from the negative stimulus. These results are consistent with discrimination, stimulus generalization, and peak-shift phenomena observed in other organisms. PMID:1940765

Attenuation of nicotine's discriminative stimulus effects in rats and its locomotor activity effects in mice by serotonergic 5-HT2A/2C receptor agonists.

PubMed

Batman, Angela M; Munzar, Patrik; Beardsley, Patrick M

2005-05-01

Reports have indicated that administration of nicotine inhibits, while withdrawal of chronically administered nicotine augments effects of serotonergic 5HT2A/2C agonists. It was our objective to determine whether 5HT2A/2C agonists can modulate the discriminative stimulus effects of nicotine in rats or its locomotor activity effects in mice. Adult male Sprague-Dawley rats were trained to discriminate 0.3 mg/kg nicotine base from saline in a two-lever, fixed-ratio (FR10), food-reinforced, operant-conditioning task during daily (Monday-Friday) 15-min experimental sessions. After characterizing a dose-response curve for nicotine, we tested the ability of the 5HT(2A/2C) agonists (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCL (DOI; 0.18-1.0 mg/kg) and 1-(4-bromo-2, 5-dimethoxyphenyl)-2-aminopropane (DOB; 0.1-1.0 mg/kg), the 5HT2C agonist 6-chloro-2-(1-piperazinyl)pyrazine hydrochloride (MK 212; 0.1 mg/kg-1.0 mg/kg), and the 5HT1A agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.01 mg/kg-1.0 mg/kg) to modulate nicotine's discriminative stimulus effects. After finding that DOI was able to attenuate the percentage nicotine lever responding (%NLR), we tested for it to also reverse nicotine's effects on locomotor activity in mice. The 5HT2A/2C agonists-in particular DOI-dose dependently attenuated %NLR. The effects of DOI were reversed by the 5HT2A/2C antagonist ketanserin. MK 212 and 8-OH-DPAT had irregular effects among rats and only reduced %NLR to below 50% levels at doses markedly suppressing responding. DOI also dose dependently blocked nicotine's acute rate-lowering locomotor activity effects. These results indicate that activation of serotonin 5HT2A/2C receptors can blunt the discriminative stimulus and locomotor activity effects of nicotine and presents the possibility that activation of these receptors might also be able to attenuate other effects of nicotine.

Creative Climate: A Leadership Lever for Innovation

ERIC Educational Resources Information Center

Isaksen, Scott G.; Akkermans, Hans J.

2011-01-01

The working atmosphere within an organization has an important influence on its level of innovative productivity. Organizational leaders influence innovative productivity as well as the climate for creativity and innovation. This exploratory study included 140 respondents from 103 different organizations, 31 industries, and 10 countries, all of…

Evaluation of study design variables and their impact on food-maintained operant responding in mice.

PubMed

Haluk, Desirae M; Wickman, Kevin

2010-03-05

Operant conditioning paradigms are useful for studying factors involved in reward, particularly when combined with the tools of genetic manipulation in mice. Published operant studies involving mice vary widely with respect to design, and insight into the consequences of design choices on performance in mice is limited. Here, we evaluated the impact of five design variables on the performance of inbred male mice in operant tasks involving solid food pellets as reinforcing agents. We found that the use of lever-press or nose-poke during FR1 sessions did not impact the performance of C57BL/6 mice, but that the lever-press approach correlated with enhanced performance during PR testing. While FR1 session duration had a notable impact on the rate of acquisition of food-maintained responding, performance during FR1 and PR sessions was largely unaffected. Higher order schedules of reinforcement (FR3 and FR5) led to elevated responding during both FR and PR sessions, and improved the correspondence between rewards earned and consumed. Single and group-housed mice performed indistinguishably during FR1 and PR sessions, while environmental enrichment combined with group housing accelerated the rate of acquisition of food-maintained responding while decreasing responding during PR testing. Finally, while C57BL/6 and 129/Sv mice exhibited comparable behavior during FR1 sessions, C57BL/6 mice tended to acquire food-maintained responding faster than 129/Sv counterparts, and exhibited elevated responding during PR testing. Altogether, our findings indicate that while operant performance for food in mice is relatively insensitive to many study parameters, experimental outcomes can be shaped predictably with proper design decisions. Copyright 2009 Elsevier B.V. All rights reserved.

Functional states of rat cortical circuits during the unpredictable availability of a reward-related cue

PubMed Central

Fernández-Lamo, Iván; Sánchez-Campusano, Raudel; Gruart, Agnès; Delgado-García M, José M.

2016-01-01

Proper performance of acquired abilities can be disturbed by the unexpected occurrence of external changes. Rats trained with an operant conditioning task (to press a lever in order to obtain a food pellet) using a fixed-ratio (1:1) schedule were subsequently placed in a Skinner box in which the lever could be removed randomly. Field postsynaptic potentials (fPSPs) were chronically evoked in perforant pathway-hippocampal CA1 (PP-CA1), CA1-subiculum (CA1-SUB), CA1-medial prefrontal cortex (CA1-mPFC), mPFC-nucleus accumbens (mPFC-NAc), and mPFC-basolateral amygdala (mPFC-BLA) synapses during lever IN and lever OUT situations. While lever presses were accompanied by a significant increase in fPSP slopes at the five synapses, the unpredictable absence of the lever were accompanied by decreased fPSP slopes in all, except PP-CA1 synapses. Spectral analysis of local field potentials (LFPs) recorded when the animal approached the corresponding area in the lever OUT situation presented lower spectral powers than during lever IN occasions for all recording sites, apart from CA1. Thus, the unpredictable availability of a reward-related cue modified the activity of cortical and subcortical areas related with the acquisition of operant learning tasks, suggesting an immediate functional reorganization of these neural circuits to address the changed situation and to modify ongoing behaviors accordingly. PMID:27869181

Activation of exchange protein activated by cAMP in the rat basolateral amygdala impairs reconsolidation of a memory associated with self-administered cocaine.

PubMed

Wan, Xun; Torregrossa, Mary M; Sanchez, Hayde; Nairn, Angus C; Taylor, Jane R

2014-01-01

The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior.

Activation of Exchange Protein Activated by cAMP in the Rat Basolateral Amygdala Impairs Reconsolidation of a Memory Associated with Self-Administered Cocaine

PubMed Central

Sanchez, Hayde; Nairn, Angus C.; Taylor, Jane R.

2014-01-01

The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how activation of Epac with 8-pCPT-cAMP (8-CPT) impacts reconsolidation of a memory that had been associated with cocaine self-administration. Rats were trained to lever press for cocaine on an FR-1 schedule, in which each cocaine delivery was paired with a tone+light cue. Lever pressing was then extinguished in the absence of cue presentations and cocaine delivery. Following the last day of extinction, rats were put in a novel context, in which the conditioned cue was presented to reactivate the cocaine-associated memory. Immediate bilateral infusions of 8-CPT into the basolateral amygdala (BLA) following reactivation disrupted subsequent cue-induced reinstatement in a dose-dependent manner, and modestly reduced responding for conditioned reinforcement. When 8-CPT infusions were delayed for 3 hours after the cue reactivation session or were given after a cue extinction session, no effect on cue-induced reinstatement was observed. Co-administration of 8-CPT and the PKA activator 6-Bnz-cAMP (10 nmol/side) rescued memory reconsolidation while 6-Bnz alone had no effect, suggesting an antagonizing interaction between the two cAMP signaling substrates. Taken together, these studies suggest that activation of Epac represents a parallel cAMP-dependent pathway that can inhibit reconsolidation of cocaine-cue memories and reduce the ability of the cue to produce reinstatement of cocaine-seeking behavior. PMID:25259911

On the automatic link between affect and tendencies to approach and avoid: Chen and Bargh (1999) revisited

PubMed Central

Rotteveel, Mark; Gierholz, Alexander; Koch, Gijs; van Aalst, Cherelle; Pinto, Yair; Matzke, Dora; Steingroever, Helen; Verhagen, Josine; Beek, Titia F.; Selker, Ravi; Sasiadek, Adam; Wagenmakers, Eric-Jan

2015-01-01

Within the literature on emotion and behavioral action, studies on approach-avoidance take up a prominent place. Several experimental paradigms feature successful conceptual replications but many original studies have not yet been replicated directly. We present such a direct replication attempt of two seminal experiments originally conducted by Chen and Bargh (1999). In their first experiment, participants affectively evaluated attitude objects by pulling or pushing a lever. Participants who had to pull the lever with positively valenced attitude objects and push the lever with negatively valenced attitude objects (i.e., congruent instruction) did so faster than participants who had to follow the reverse (i.e., incongruent) instruction. In Chen and Bargh's second experiment, the explicit evaluative instructions were absent and participants merely responded to the attitude objects by either always pushing or always pulling the lever. Similar results were obtained as in Experiment 1. Based on these findings, Chen and Bargh concluded that (1) attitude objects are evaluated automatically; and (2) attitude objects automatically trigger a behavioral tendency to approach or avoid. We attempted to replicate both experiments and failed to find the effects reported by Chen and Bargh as indicated by our pre-registered Bayesian data analyses; nevertheless, the evidence in favor of the null hypotheses was only anecdotal, and definitive conclusions await further study. PMID:25883572

Discrimination of Variable Schedules Is Controlled by Interresponse Times Proximal to Reinforcement

ERIC Educational Resources Information Center

Tanno, Takayuki; Silberberg, Alan; Sakagami, Takayuki

2012-01-01

In Experiment 1, food-deprived rats responded to one of two schedules that were, with equal probability, associated with a sample lever. One schedule was always variable ratio, while the other schedule, depending on the trial within a session, was: (a) a variable-interval schedule; (b) a tandem variable-interval,…

Suppressive and Facilitative Effects of Shock Intensity and Interresponse Times Followed by Shock

ERIC Educational Resources Information Center

Everly, Jessica B.; Perone, Michael

2012-01-01

Although response-dependent shock often suppresses responding, response facilitation can occur. In two experiments, we examined the suppressive and facilitative effects of shock by manipulating shock intensity and the interresponse times that produced shock. Rats' lever presses were reinforced on a variable-interval 40-s schedule of food…

The Road to Resilience: Insights on Training Community Coalitions in the Los Angeles County Community Disaster Resilience Project.

PubMed

Cha, Biblia S; Lawrence, Rachel I; Bliss, Jesse C; Wells, Kenneth B; Chandra, Anita; Eisenman, David P

2016-12-01

Local health departments (LHDs) have little guidance for operationalizing community resilience (CR). We explored how community coalitions responded to 4 CR levers (education, engagement, partnerships, and community self-sufficiency) during the first planning year of the Los Angeles County Community Disaster Resilience (LACCDR) Project. Sixteen communities were selected and randomly assigned to the experimental CR group or the control preparedness group. Eight CR coalitions met monthly to plan CR-building activities or to receive CR training from a public health nurse. Trained observers documented the coalitions' understanding and application of CR at each meeting. Qualitative content analysis was used to analyze structured observation reports around the 4 levers. Analysis of 41 reports suggested that coalitions underwent a process of learning about and applying CR concepts in the planning year. Groups resonated with ideas of education, community self-sufficiency, and engagement, but increasing partnerships was challenging. LHDs can support coalitions by anticipating the time necessary to understand CR and by facilitating engagement. Understanding the issues that emerge in the early phases of planning and implementing CR-building activities is critical. LHDs can use the experience of the LACCDR Project's planning year as a guide to navigate challenges and issues that emerge as they operationalize the CR model. (Disaster Med Public Health Preparedness. 2016;10:812-821).

Regulatory light chain mutants linked to heart disease modify the cardiac myosin lever arm.

PubMed

Burghardt, Thomas P; Sikkink, Laura A

2013-02-19

Myosin is the chemomechanical energy transducer in striated heart muscle. The myosin cross-bridge applies impulsive force to actin while consuming ATP chemical energy to propel myosin thick filaments relative to actin thin filaments in the fiber. Transduction begins with ATP hydrolysis in the cross-bridge driving rotary movement of a lever arm converting torque into linear displacement. Myosin regulatory light chain (RLC) binds to the lever arm and modifies its ability to translate actin. Gene sequencing implicated several RLC mutations in heart disease, and three of them are investigated here using photoactivatable GFP-tagged RLC (RLC-PAGFP) exchanged into permeabilized papillary muscle fibers. A single-lever arm probe orientation is detected in the crowded environment of the muscle fiber by using RLC-PAGFP with dipole orientation deduced from the three-spatial dimension fluorescence emission pattern of the single molecule. Symmetry and selection rules locate dipoles in their half-sarcomere, identify those at the minimal free energy, and specify active dipole contraction intermediates. Experiments were performed in a microfluidic chamber designed for isometric contraction, total internal reflection fluorescence detection, and two-photon excitation second harmonic generation to evaluate sarcomere length. The RLC-PAGFP reports apparently discretized lever arm orientation intermediates in active isometric fibers that on average produce the stall force. Disease-linked mutants introduced into RLC move intermediate occupancy further down the free energy gradient, implying lever arms rotate more to reach stall force because mutant RLC increases lever arm shear strain. A lower free energy intermediate occupancy involves a lower energy conversion efficiency in the fiber relating a specific myosin function modification to the disease-implicated mutant.

Altered operant responding for motor reinforcement and the determination of benchmark doses following perinatal exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin.

PubMed

Markowski, V P; Zareba, G; Stern, S; Cox, C; Weiss, B

2001-06-01

Pregnant Holtzman rats were exposed to a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the 18th day of gestation. Their adult female offspring were trained to respond on a lever for brief opportunities to run in specially designed running wheels. Once they had begun responding on a fixed-ratio 1 (FR1) schedule of reinforcement, the fixed-ratio requirement for lever pressing was increased at five-session intervals to values of FR2, FR5, FR10, FR20, and FR30. We examined vaginal cytology after each behavior session to track estrous cyclicity. Under each of the FR values, perinatal TCDD exposure produced a significant dose-related reduction in the number of earned opportunities to run, the lever response rate, and the total number of revolutions in the wheel. Estrous cyclicity was not affected. Because of the consistent dose-response relationship at all FR values, we used the behavioral data to calculate benchmark doses based on displacements from modeled zero-dose performance of 1% (ED(01)) and 10% (ED(10)), as determined by a quadratic fit to the dose-response function. The mean ED(10) benchmark dose for earned run opportunities was 10.13 ng/kg with a 95% lower bound of 5.77 ng/kg. The corresponding ED(01) was 0.98 ng/kg with a 95% lower bound of 0.83 ng/kg. The mean ED(10) for total wheel revolutions was calculated as 7.32 ng/kg with a 95% lower bound of 5.41 ng/kg. The corresponding ED(01) was 0.71 ng/kg with a 95% lower bound of 0.60. These values should be viewed from the perspective of current human body burdens, whose average value, based on TCDD toxic equivalents, has been calculated as 13 ng/kg.

Preference pulses and the win-stay, fix-and-sample model of choice.

PubMed

Hachiga, Yosuke; Sakagami, Takayuki; Silberberg, Alan

2015-11-01

Two groups of six rats each were trained to respond to two levers for a food reinforcer. One group was trained on concurrent variable-ratio 20 extinction schedules of reinforcement. The second group was trained on a concurrent variable-interval 27-s extinction schedule. In both groups, lever-schedule assignments changed randomly following reinforcement; a light cued the lever providing the next reinforcer. In the next condition, the light cue was removed and reinforcer assignment strictly alternated between levers. The next two conditions redetermined, in order, the first two conditions. Preference pulses, defined as a tendency for relative response rate to decline to the just-reinforced alternative with time since reinforcement, only appeared during the extinction schedule. Although the pulse's functional form was well described by a reinforcer-induction equation, there was a large residual between actual data and a pulse-as-artifact simulation (McLean, Grace, Pitts, & Hughes, 2014) used to discern reinforcer-dependent contributions to pulsing. However, if that simulation was modified to include a win-stay tendency (a propensity to stay on the just-reinforced alternative), the residual was greatly reduced. Additional modifications of the parameter values of the pulse-as-artifact simulation enabled it to accommodate the present results as well as those it originally accommodated. In its revised form, this simulation was used to create a model that describes response runs to the preferred alternative as terminating probabilistically, and runs to the unpreferred alternative as punctate with occasional perseverative response runs. After reinforcement, choices are modeled as returning briefly to the lever location that had been just reinforced. This win-stay propensity is hypothesized as due to reinforcer induction. © Society for the Experimental Analysis of Behavior.

Autoshaping i.v. cocaine self-administration in rats: effects of nondrug alternative reinforcers on acquisition.

PubMed

Carroll, M E; Lac, S T

1993-01-01

The purpose of this experiment was to examine the effects of a nondrug alternative reinforcer and feeding conditions on the acquisition of cocaine self-administration. Rats were autoshaped to press a lever that resulted in a 0.2 mg/kg i.v. cocaine infusion. Responses on the lever were monitored during six consecutive autoshaping sessions that occurred each day. A retractable lever was inserted into the operant chamber on a random time 60 s schedule 10 times per session for six sessions that began each hour. Each day the six autoshaping sessions were followed by a 6-h cocaine self-administration session. During self-administration the lever remained extended, and each response on the lever resulted in a cocaine infusion (0.2 mg/kg). The criterion for acquisition of cocaine-reinforced behavior was met when there were 5 consecutive days during which the mean number of infusions during the 6-h self-administration session was at least 100. This procedure was repeated daily until the criterion was met or 30 days elapsed. The rats were also trained to respond on lick-operated automatic drinking devices that delivered 0.05 ml water or a glucose and saccharin solution (G + S) contingent upon each lick response. Five groups of 12-14 rats were compared. The first four groups constituted a 2 x 2 factorial design whereby either G + S or water was available in the home cage for 3 weeks before autoshaping began and G + S or water was available in the operant chamber during autoshaping. These groups were limited to 20 g food per day and all had free access to water.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of alcohol and saccharin deprivations on concurrent ethanol and saccharin operant self-administration by alcohol-preferring (P) rats.

PubMed

Toalston, Jamie E; Oster, Scott M; Kuc, Kelly A; Pommer, Tylene J; Murphy, James M; Lumeng, Lawrence; Bell, Richard L; McBride, William J; Rodd, Zachary A

2008-06-01

Consumption of sweet solutions has been associated with a reduction in withdrawal symptoms and alcohol craving in humans. The objective of the present study was to determine the effects of ethanol and saccharin (SACC) deprivations on operant oral self-administration. Alcohol-preferring (P) rats were allowed to lever press concurrently self-administer ethanol (15% vol/vol) and SACC (0.0125% g/vol) for 8 weeks. Rats were then maintained on daily operant access (nondeprived), deprived of both fluids (2 weeks), deprived of SACC and given 2 ml of ethanol daily, or deprived of ethanol and given 2 ml of SACC daily. All groups were then given 2 weeks of daily operant access to ethanol and SACC, followed by an identical second deprivation period. P rats responded more for ethanol than SACC. All deprived groups increased responding on the ethanol lever, but not on the SACC lever. Daily consumption of 2 ml ethanol decreased the duration of the alcohol deprivation effect (ADE). Home cage access to 2 ml of SACC also decreased the ADE but to a lesser extent than access to ethanol. A second deprivation period further increased and prolonged the expression of an ADE. These results show ethanol is a more salient reinforcer than SACC. With concurrent access to ethanol and SACC, P rats do not display a saccharin deprivation effect. Depriving P rats of both ethanol and SACC had the most pronounced effect on the magnitude and duration of the ADE, suggesting that there may be some interactions between ethanol and SACC in their CNS reinforcing effects.

Self-administration of cocaine and remifentanil by monkeys under concurrent-access conditions.

PubMed

Huskinson, Sally L; Freeman, Kevin B; Woolverton, William L

2015-01-01

Cocaine and opioids are often co-abused. Laboratory research has focused largely on the reinforcing effects of mixtures of drugs relative to the drugs alone. Less research has examined drug mixing by the subject under concurrent-access conditions. Self-administration of various doses of cocaine and remifentanil was examined under concurrent-access conditions. It was hypothesized that if cocaine and opioid combinations were more effective reinforcers than the single drugs, subjects would mix the two drugs by adjusting their responding to cocaine and an opioid alternative to maintain an optimal ratio of cocaine/remifentanil intake. Three male rhesus monkeys were allowed to self-administer cocaine (0.05-0.2 mg/kg/inj) or saline on one lever and remifentanil (0.05-0.4 μg/kg/inj) or saline on the other lever under concurrent fixed-ratio (FR) 10 schedules. Daily sessions lasted 2 h, and there was a 1-s timeout after every 10-s injection. When saline and drug were concurrently available, responding on the saline-associated lever was low relative to the drug alternative. When cocaine and remifentanil were concurrently available, both drugs were self-administered above saline levels. Cocaine intake decreased, and remifentanil intake increased as a function of the remifentanil dose that was available. Conversely, cocaine intake and remifentanil intake did not change systematically as a function of the cocaine dose that was available. Monkeys will mix cocaine and an opioid when the two drugs are available concurrently. However, there was no indication that monkeys titrated drug intake to maintain an optimal ratio of intake of the two compounds.

Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive.

PubMed

Campbell, Erin J; Mitchell, Caitlin S; Adams, Cameron D; Yeoh, Jiann Wei; Hodgson, Deborah M; Graham, Brett A; Dayas, Christopher V

2017-10-01

Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here, we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations. Male rat pups were maternally separated for 0 or 3 h on postnatal days 2-14. During adolescence, rats received bilateral injections of hM3D(Gq), the excitatory designer receptor exclusively activated by designer drugs, into LH. In adulthood, rats were trained to self-administer sucrose and tested under a progressive ratio schedule to determine their motivation for reward following injection with either vehicle or 5 mg/kg clozapine-N-oxide. Brains were processed for Fos-protein immunohistochemistry. ELS significantly suppressed lever responding for sucrose, indicating a long-lasting impact of ELS on motivation circuits. hM3D(Gq) activation of LH increased responding, normalizing deficits in ELS rats, and increased Fos-positive orexin and MCH cell numbers within LH. Our findings indicate that despite being susceptible to environmental stressors, LH circuits retain the capacity to overcome ELS-induced deficits in motivated behaviour. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Precipitated withdrawal from nicotine reduces reinforcing effects of a visual stimulus for rats.

PubMed

Weaver, Matthew T; Sweitzer, Maggie; Coddington, Sarah; Sheppard, Jaimee; Verdecchia, Nicole; Caggiula, Anthony R; Sved, Alan F; Donny, Eric C

2012-07-01

Research has identified at least two positive reinforcement-related effects of nicotine: (a) primary reinforcement and (b) enhancement of reinforcement from concurrently available stimuli. Prior examples of the reinforcement-enhancing effects with rats showed that repeated, intermittent nicotine exposure increased responding for non-nicotine reinforcers, and this effect remained robust over several weeks. However, the effects of continuous nicotine exposure on responding for a non-nicotine reinforcer are unknown, as are the effects of abruptly withdrawing continuous nicotine on behavior maintained by the same reinforcer. Lever pressing for a visual reinforcer under a fixed ratio schedule was assessed while rats were maintained on a chronic, continuous infusion of nicotine (3.16 mg/kg/day; osmotic minipump). The effects of precipitated withdrawal on responding, following 16 days of continuous nicotine exposure, were assessed by pre-session subcutaneous injections of mecamylamine (1.0 mg/kg). Continuous nicotine initially increased active responding for the visual reinforcer; however, continued exposure resulted in an attenuation of this effect. Precipitated withdrawal from nicotine resulted in a significant decline in active responding. The initial increase in responding for the visual reinforcer with chronic nicotine exposure is consistent with prior research showing that intermittent exposure to nicotine acts as a reinforcement enhancer. However, the attenuation of this enhancement following prolonged nicotine exposure is in contrast with the persistent effects previously reported. Finally, the decrease in visual reinforcers below control levels (nicotine-naive animals) following nicotine withdrawal highlights a potential for affective withdrawal, which may serve as a motive for continued nicotine use.

The Mean as the Balance Point: Thought Experiments with Measuring Sticks

ERIC Educational Resources Information Center

Flores, A.

2008-01-01

This article presents activities to help students establish a connection between the mean and the balance point of a lever. The lever and its law are discussed briefly. Thought experiments with a meterstick are presented to emphasize different properties of the mean and weighted averages. (Contains 16 figures.)

Dopamine Modulates Reward Expectancy During Performance of a Slot Machine Task in Rats: Evidence for a ‘Near-miss' Effect

PubMed Central

Winstanley, Catharine A; Cocker, Paul J; Rogers, Robert D

2011-01-01

Cognitive accounts of gambling suggest that the experience of almost winning—so-called ‘near-misses'—encourage continued play and accelerate the development of pathological gambling (PG) in vulnerable individuals. One explanation for this effect is that near-misses signal imminent winning outcomes and heighten reward expectancy, galvanizing further play. Determining the neurochemical processes underlying the drive to gamble could facilitate the development of more effective treatments for PG. With this aim in mind, we evaluated rats' performance on a novel model of slot machine play, a form of gambling in which near-miss events are particularly salient. Subjects responded to a series of three flashing lights, loosely analogous to the wheels of a slot machine, causing the lights to set to ‘on' or ‘off'. A winning outcome was signaled if all three lights were illuminated. At the end of each trial, rats chose between responding on the ‘collect' lever, resulting in reward on win trials, but a time penalty on loss trials, or starting a new trial. Rats showed a marked preference for the collect lever when both two and three lights were illuminated, indicating heightened reward expectancy following near-misses similar to wins. Erroneous collect responses were increased by amphetamine and the D2 receptor agonist quinpirole, but not by the D1 receptor agonist SKF 81297 or receptor subtype selective antagonists. These data suggest that dopamine modulates reward expectancy following the experience of almost winning during slot machine play, via activity at D2 receptors, and this may result in an enhancement of the near-miss effect and facilitate further gambling. PMID:21209612

Dopamine modulates reward expectancy during performance of a slot machine task in rats: evidence for a 'near-miss' effect.

PubMed

Winstanley, Catharine A; Cocker, Paul J; Rogers, Robert D

2011-04-01

Cognitive accounts of gambling suggest that the experience of almost winning-so-called 'near-misses'-encourage continued play and accelerate the development of pathological gambling (PG) in vulnerable individuals. One explanation for this effect is that near-misses signal imminent winning outcomes and heighten reward expectancy, galvanizing further play. Determining the neurochemical processes underlying the drive to gamble could facilitate the development of more effective treatments for PG. With this aim in mind, we evaluated rats' performance on a novel model of slot machine play, a form of gambling in which near-miss events are particularly salient. Subjects responded to a series of three flashing lights, loosely analogous to the wheels of a slot machine, causing the lights to set to 'on' or 'off'. A winning outcome was signaled if all three lights were illuminated. At the end of each trial, rats chose between responding on the 'collect' lever, resulting in reward on win trials, but a time penalty on loss trials, or starting a new trial. Rats showed a marked preference for the collect lever when both two and three lights were illuminated, indicating heightened reward expectancy following near-misses similar to wins. Erroneous collect responses were increased by amphetamine and the D(2) receptor agonist quinpirole, but not by the D(1) receptor agonist SKF 81297 or receptor subtype selective antagonists. These data suggest that dopamine modulates reward expectancy following the experience of almost winning during slot machine play, via activity at D(2) receptors, and this may result in an enhancement of the near-miss effect and facilitate further gambling.

Effects of fendiline on cocaine-seeking behavior in the rat.

PubMed

Cunningham, Jonathan J; Orr, Erin; Lothian, Barbara C; Morgen, Jennifer; Brebner, Karen

2015-12-01

L-type Ca(2+) channels (LTCC) and GABAB receptors are both possible targets in the development of new pharmacological compounds for cocaine addiction. Drugs that target either receptor attenuate a wide range of cocaine-seeking behaviors in the rat. However, there is no current human-approved pharmacotherapeutic intervention for psychostimulant addiction. This study examined the effects of a human-approved LTCC blocker, fendiline, on cocaine-taking and cocaine-seeking behavior in rats. The effects of combining fendiline with the GABAB receptor agonist baclofen on cocaine self-administration were also tested. Male Wistar rats were trained to self-administer cocaine, and the effects of fendiline pretreatment (vehicle, 1.78, 3.16, 5.62 mg/kg, intraperitoneal (IP)) were tested on progressive ratio responding and cue- and drug-induced reinstatement. The effects of baclofen (vehicle, 0.56, 1.78, 3.16, 5.62 mg/kg, IP) combined with fendiline (5.62 mg/kg, IP) were tested on progressive ratio responding. Control experiments measured locomotor activity and lever pressing for food in rats that received both baclofen and fendiline prior to the test session. Acute injections of fendiline prior to cue- or drug-induced reinstatement significantly attenuated lever-pressing behavior (p < 0.05). Fendiline and baclofen, but not fendiline alone, not only significantly attenuated breakpoints, but also impaired general motor behavior and naturalistic reinforcement (p < 0.05). These data suggest that the LTCC blocker fendiline may represent a novel pharmacotherapeutic intervention to prevent reinstatement to cocaine seeking. Also, co-administration of fendiline and baclofen not only can attenuate the motivation to take cocaine, but also impairs general motor behavior and naturalistic reinforcement.

Characterization of the discriminative stimulus produced by the dopamine antagonist tiapride.

PubMed

Cohen, C; Sanger, D J; Perrault, G

1997-11-01

The ability of tiapride, a selective D2/D3 dopamine receptor antagonist, to exert discriminative stimulus control of responding was investigated by training rats to discriminate this drug (30 mg/kg) from saline in a two-lever, food-reinforcement procedure. Acquisition of tiapride discrimination required a relatively lengthy training period (mean of 76 sessions) but stable performance was maintained throughout the 18- month study. The dose of tiapride eliciting 50% tiapride-lever choice (ED50) was 2.2 mg/kg. After determination of the dose-effect curve with tiapride, substitution tests with several dopamine antagonists and other reference compounds were performed. All dopamine antagonists, including amisulpride (ED50 4 mg/kg), sulpiride (18 mg/kg), sultopride (1.5 mg/kg), clebopride (0.13 mg/kg), raclopride (0.16 mg/kg), metoclopramide (1.4 mg/kg), remoxipride (4.8 mg/kg), pimozide (2.7 mg/kg), thioridazine (3.4 mg/kg), olanzapine (0.97 mg/kg), chlorpromazine (1.9 mg/kg), risperidone (0.22 mg/kg) and haloperidol (0.14 mg/kg), except clozapine (>10 mg/kg), produced dose-dependent substitution for tiapride. Tiapride-like stimulus effects were observed at doses that decreased response rates. However, ED50 values for substitution by tiapride, amisulpride, sulpiride, sultopride, pimozide, clebopride and thioridazine were lower than ED50 values for decreasing responding. Additional studies were conducted to evaluate the ability of direct and indirect dopamine agonists to attenuate the tiapride discriminative stimulus. Pretreatment with d-amphetamine and nomifensine antagonized the discriminative stimulus effects of tiapride. Quinpirole, 7-OH-DPAT, bromocriptine and apomorphine partially blocked the stimulus effects of tiapride whereas SKF 38393 did not affect the discrimination. These results from substitution and antagonism tests indicated that the discriminative effects of tiapride are mediated by activity at D2/D3 dopamine receptors.

Aid and Innovation: How Federal Financial Aid Policy Impacts Student Success and How States Can Respond. Policy Bulletin

ERIC Educational Resources Information Center

Reichert, Katrina

2012-01-01

From Washington to Connecticut, Arkansas to Indiana, state policymakers and community college leaders are focused on building completion pathways to ensure that more students succeed in postsecondary education and make smooth transitions to careers. Financial aid is both an effective and a necessary policy lever to promote this goal. Not only do…

Discriminative stimulus effects of the imidazoline I2 receptor ligands BU224 and phenyzoline in rats.

PubMed

Qiu, Yanyan; Zhang, Yanan; Li, Jun-Xu

2015-02-15

Although imidazoline I2 receptor ligands have been used as discriminative stimuli, the role of efficacy of I2 receptor ligands as a critical determinant in drug discrimination has not been explored. This study characterized the discriminative stimulus effects of selective imidazoline I2 receptor ligands BU224 (a low-efficacy I2 receptor ligand) and phenyzoline (a higher efficacy I2 receptor ligand) in rats. Two groups of male Sprague-Dawley rats were trained to discriminate 5.6mg/kg BU224 or 32mg/kg phenyzoline (i.p.) from their vehicle in a two-lever food-reinforced drug discrimination procedure, respectively. All rats acquired the discriminations after an average of 18 (BU224) and 56 (phenyzoline) training sessions, respectively. BU224 and phenyzoline completely substituted for one another symmetrically. Several I2 receptor ligands (tracizoline, CR4056, RS45041, and idazoxan) all occasioned>80% drug-associated lever responding in both discriminations. The I2 receptor ligand 2-BFI and a monoamine oxidase inhibitor harmane occasioned>80% drug-associated lever responding in rats discriminating BU224. Other drugs that occasioned partial or less substitution to BU224 cue included clonidine, methamphetamine, ketamine, morphine, methadone and agmatine. Clonidine, methamphetamine and morphine also only produced partial substitution to phenyzoline cue. Naltrexone, dopamine D2 receptor antagonist haloperidol and serotonin (5-HT)2A receptor antagonist MDL100907 failed to alter the discriminative stimulus effects of BU224 or phenyzoline. Combined, these results are the first to demonstrate that BU224 and phenyzoline can serve as discriminative stimuli and that the low-efficacy I2 receptor ligand BU224 shares similar discriminative stimulus effects with higher-efficacy I2 receptor ligands such as phenyzoline and 2-BFI. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of the cholinergic system in the signal attenuation rat model of obsessive-compulsive disorder.

PubMed

Yankelevitch-Yahav, Roni; Roni, Yankelevitch-Yahav; Joel, Dapha; Daphna, Joel

2013-11-01

In comparison to studies of the involvement of the serotonergic, dopaminergic, and glutamatergic systems in the pathophysiology of obsessive-compulsive disorder (OCD), research on the involvement of the cholinergic system in this disorder has remained sparse. The aim of this study was to test the role of the cholinergic system in compulsive behavior using the signal attenuation rat model of OCD. In this model, "compulsive" behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. The acetylcholinesterase inhibitor physostigmine (0.05, 0.10, and 0.15 mg/kg), the nicotinic agonist nicotine (0.03, 0.06, 0.10, 0.30, 0.60, and 1.00 mg/kg), the nicotinic antagonist mecamylamine (1, 3, 5, and 8 mg/kg), the muscarinic agonist oxotremorine (0.0075, 0.0150, and 0.0300 mg/kg), and the muscarinic antagonist scopolamine (0.15, 0.50, 1.00, and 1.50 mg/kg) were acutely administered to rats just before assessing their lever-press responding following signal attenuation (experiments 1, 3, 5, 7, and 9, respectively). Because the effects of signal attenuation are assessed under extinction conditions, drug doses that were effective in the above experiments were also tested in an extinction session of lever-press responding that was not preceded by signal attenuation (experiments 2, 4, 6, 8, and 10). Acute systemic administration of the cholinergic agents did not exert a selective anti- or pro-compulsive effect in the signal attenuation model. Acetylcholine does not seem to play a role in the signal attenuation rat model of OCD.

Disruptions in effort-based decision-making and consummatory behavior following antagonism of the dopamine D2 receptor.

PubMed

Robles, Cindee F; Johnson, Alexander W

2017-03-01

Dopamine is known to influence motivational processes, however the precise role of this neurotransmitter remains a contentious issue. In the current study we sought to further characterize dopamine signaling in reward-based decision-making and consummatory behavior in mice, via lateral ventricle infusion of the dopamine D2 receptor antagonist eticlopride. In Experiment 1, we examined effort-based decision-making, in which mice had a choice between one lever, where a single response led to the delivery of a low value reward (2% sucrose); and a second lever, which led to a higher value reward (20% sucrose) that gradually required more effort to obtain. As the response schedule for the high value reward became more strict, low dose (4μg in 0.5μl) central infusions of eticlopride biased preference away from the high value reward, and toward the lever that led to the low value reward. Similarly, a higher dose of eticlopride (8μg in 0.5μl) also disrupted choice responding for the high value reward, however it did so by increasing omissions. In Experiment 2, we assessed the effects of eticlopride on consumption of 20% sucrose. The antagonist led to a dose-dependent reduction in intake, and through an analysis of licking microstructure, it was revealed that this in part reflected a reduction in the motivation to engage in consummatory behavior, rather than alterations in the evaluation of the reward. These results suggest that disruptions in D2 receptor signaling reduce the willingness to engage in effortful operant responding and consumption of a desirable outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

A wheelchair with lever propulsion control for climbing up and down stairs.

PubMed

Sasaki, Kai; Eguchi, Yosuke; Suzuki, Kenji

2016-08-01

This study proposes a novel stair-climbing wheelchair based on lever propulsion control using the human upper body. Wheelchairs are widely used as supporting locomotion devices for people with acquired lower limb disabilities. However, steps and stairs are critical obstacles to locomotion, which restrict their activities when using wheelchairs. Previous research focused on power-assisted, stair-climbing wheelchairs, which were large and heavy due to its large actuators and mechanisms. In the previous research, we proposed a wheelchair with lever propulsion mechanism and presented its feasibility of climbing up the stairs. The developed stair-climbing wheelchair consists of manual wheels with casters for planar locomotion and a rotary-leg mechanism based on lever propulsion that is capable of climbing up stairs. The wheelchair also has a passive mechanism powered by gas springs for posture transition to shift the user's center of gravity between the desired positions for planar locomotion and stair-climbing. In this paper, we present an advanced study on both climbing up and going down using lever propulsion control by the user's upper body motion. For climbing down the stairs, we reassembled one-way clutches used for the rotary-leg mechanism to help a user climb down the stairs through lever operation. We also equipped the wheelchair with sufficient torque dampers. The frontal wheels were fixed while climbing down the stairs to ensure safety. Relevant experiments were then performed to investigate its performance and verify that the wheelchair users can operate the proposed lever propulsion mechanism.

In vivo myosin step-size from zebrafish skeletal muscle

PubMed Central

Ajtai, Katalin; Sun, Xiaojing; Takubo, Naoko; Wang, Yihua

2016-01-01

Muscle myosins transduce ATP free energy into actin displacement to power contraction. In vivo, myosin side chains are modified post-translationally under native conditions, potentially impacting function. Single myosin detection provides the ‘bottom-up’ myosin characterization probing basic mechanisms without ambiguities inherent to ensemble observation. Macroscopic muscle physiological experimentation provides the definitive ‘top-down’ phenotype characterizations that are the concerns in translational medicine. In vivo single myosin detection in muscle from zebrafish embryo models for human muscle fulfils ambitions for both bottom-up and top-down experimentation. A photoactivatable green fluorescent protein (GFP)-tagged myosin light chain expressed in transgenic zebrafish skeletal muscle specifically modifies the myosin lever-arm. Strychnine induces the simultaneous contraction of the bilateral tail muscles in a live embryo, causing them to be isometric while active. Highly inclined thin illumination excites the GFP tag of single lever-arms and its super-resolution orientation is measured from an active isometric muscle over a time sequence covering many transduction cycles. Consecutive frame lever-arm angular displacement converts to step-size by its product with the estimated lever-arm length. About 17% of the active myosin steps that fall between 2 and 7 nm are implicated as powerstrokes because they are beyond displacements detected from either relaxed or ATP-depleted (rigor) muscle. PMID:27249818

First-Class Inquiry

ERIC Educational Resources Information Center

Hesser, Kathi; Buck, Gayle; Dopp, Sandra

2005-01-01

In the activity described in this article, students will explore how variables in a first-class lever, specifically arm length, position of the fulcrum, and placement of the load, affect the effort needed to lift the load. To begin the lesson, demonstrate to the class how a first-class lever works and review what is meant by the terms fulcrum,…

Normative social influence is underdetected.

PubMed

Nolan, Jessica M; Schultz, P Wesley; Cialdini, Robert B; Goldstein, Noah J; Griskevicius, Vladas

2008-07-01

The present research investigated the persuasive impact and detectability of normative social influence. The first study surveyed 810 Californians about energy conservation and found that descriptive normative beliefs were more predictive of behavior than were other relevant beliefs, even though respondents rated such norms as least important in their conservation decisions. Study 2, a field experiment, showed that normative social influence produced the greatest change in behavior compared to information highlighting other reasons to conserve, even though respondents rated the normative information as least motivating. Results show that normative messages can be a powerful lever of persuasion but that their influence is underdetected.

Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks

PubMed Central

Sanabria, Federico; Killeen, Peter R

2008-01-01

Background The inability to inhibit reinforced responses is a defining feature of ADHD associated with impulsivity. The Spontaneously Hypertensive Rat (SHR) has been extolled as an animal model of ADHD, but there is no clear experimental evidence of inhibition deficits in SHR. Attempts to demonstrate these deficits may have suffered from methodological and analytical limitations. Methods We provide a rationale for using two complementary response-withholding tasks to doubly dissociate impulsivity from motivational and motor processes. In the lever-holding task (LHT), continual lever depression was required for a minimum interval. Under a differential reinforcement of low rates schedule (DRL), a minimum interval was required between lever presses. Both tasks were studied using SHR and two normotensive control strains, Wistar-Kyoto (WKY) and Long Evans (LE), over an overlapping range of intervals (1 – 5 s for LHT and 5 – 60 s for DRL). Lever-holding and DRL performance was characterized as the output of a mixture of two processes, timing and iterative random responding; we call this account of response inhibition the Temporal Regulation (TR) model. In the context of TR, impulsivity was defined as a bias toward premature termination of the timed intervals. Results The TR model provided an accurate description of LHT and DRL performance. On the basis of TR parameter estimates, SHRs were more impulsive than LE rats across tasks and target times. WKY rats produced substantially shorter timed responses in the lever-holding task than in DRL, suggesting a motivational or motor deficit. The precision of timing by SHR, as measured by the variance of their timed intervals, was excellent, flouting expectations from ADHD research. Conclusion This research validates the TR model of response inhibition and supports SHR as an animal model of ADHD-related impulsivity. It indicates, however, that SHR's impulse-control deficit is not caused by imprecise timing. The use of ad hoc impulsivity metrics and of WKY as control strain for SHR impulsivity are called into question. PMID:18261220

Problem Implementation as a Lever for Change: An Experimental Study of the Effects of a Professional Development Program on Students' Mathematics Learning

ERIC Educational Resources Information Center

Santagata, Rossella; Kersting, Nicole; Givvin, Karen B.; Stigler, James W.

2011-01-01

This study investigates, through an experimental design, the effectiveness of a professional development program on teacher knowledge and practices and on student learning. The program consisted of a series of video-based modules designed to respond to needs of U.S. teachers, as highlighted by findings from the 1999 Third International Mathematics…

Pavlovian-Instrumental Transfer of the Discriminative Stimulus Effects of Nicotine and Ethanol in Rats

ERIC Educational Resources Information Center

Troisi, Joseph R., II

2006-01-01

To date, only 1 study has evaluated the impact of a Pavlovian drug conditional stimulus (CS) on operant responding. A within-subject operant 1-lever go/no-go (across sessions) design was used to evaluate the impact of Pavlovian contingencies on the discriminative stimulus effects of nicotine (0.4 mg/kg) and ethanol (800 mg/kg) in male Sprague…

Hezbollah: Social Services as a Source of Power

DTIC Science & Technology

2010-06-01

USSOF conducts special operations to prepare the oper- ational environment, prevent crisis, and respond with speed, aggression, and lethality to...International Relations from Troy State University, and Master of Military Arts and Science in Campaign Design from the U.S. Army Command and General Staff...movement into a stateless government that lever- ages charity to meet the needs of the neglected, oppressed, and marginalized Lebanese Shi’a

Renewal after the punishment of free operant behavior.

PubMed

Bouton, Mark E; Schepers, Scott T

2015-01-01

Three experiments examined the role of context in punishment learning. In Experiment 1, rats were trained to lever press for food in Context A and then punished for responding in Context B (by presenting response-contingent footshock). Punishment led to complete suppression of the response. However, when responding was tested (in extinction) in Contexts A and B, a strong renewal of responding occurred in Context A. In Experiment 2, renewal also occurred when initial reinforcement occurred in Context A, punishment occurred in Context B, and testing occurred in a new context (Context C). In both experiments, behavioral suppression and renewal were not observed in groups that received noncontingent (yoked) footshocks in Context B. In Experiment 3, 2 responses (lever press and chain pull) were separately reinforced in Contexts A and B and then punished in the opposite context. Although the procedure equated the contexts on their association with reinforcement and punishment, renewal of each response was observed when it was tested in its nonpunished context. The contexts also influenced response choice. Overall, the results suggest that punishment is specific to the context in which it is learned, and establish that its context-specificity does not depend on a simple association between the context and shock. Like extinction, punishment may involve learning to inhibit a specific response in a specific context. Implications for theories of punishment and for understanding the cessation of problematic operant behavior (e.g., drug abuse) are discussed. PsycINFO Database Record (c) 2015 APA, all rights reserved.

The effects of varied extinction procedures on contingent cue-induced reinstatement in Sprague-Dawley rats.

PubMed

Buffalari, Deanne M; Feltenstein, Matthew W; See, Ronald E

2013-11-01

Cue exposure therapy, which attempts to limit relapse by reducing reactivity to cocaine-paired cues through repeated exposures, has had limited success. The current experiments examined cocaine cue-induced anxiogenesis and investigated whether a model of cue exposure therapy would reduce reinstatement of cocaine seeking in rats with a history of cocaine self-administration. Male rats experienced daily intravenous cocaine self-administration. Rats then experienced exposure to either the self-administration context or the context plus noncontingent presentations of cocaine-paired cues. Immediately following exposure, anxiety-like behavior was measured using elevated plus maze and defensive burying tests. In a second group of rats, self-administration was followed by 7 days of exposure to the context, context + noncontingent cue exposure, lever extinction, or cue + lever extinction. All animals then underwent two contingent cue-induced reinstatement tests separated by 7 days of lever extinction. Exposure to noncontingent cocaine-paired cues in the self-administration context increased anxiety-like behavior on the defensive burying test. Animals that experienced lever + cue extinction displayed the least cocaine seeking on the first reinstatement test, and lever extinction reduced cocaine seeking below context exposure or context + noncontingent cue exposure. All animals had similar levels of cocaine seeking on the second reinstatement test. Noncontingent cue exposure causes anxiety, and noncontingent cue and context exposure are less effective at reducing contingent cue-induced reinstatement than lever or lever + cue extinction. These data indicate that active extinction of the drug-taking response may be critical for reduction of relapse proclivity in former cocaine users.

Disruptive effects of prefeeding and haloperidol administration on multiple measures of food-maintained behavior in rats

PubMed Central

Hayashi, Yusuke; Wirth, Oliver

2015-01-01

Four rats responded under a choice reaction-time procedure. At the beginning of each trial, the rats were required to hold down a center lever for a variable duration, release it following a high- or low-pitched tone, and press either a left or right lever, conditionally on the tone. Correct choices were reinforced with a probability of .95 or .05 under blinking or static houselights, respectively. After performance stabilized, disruptive effects of free access to food pellets prior to sessions (prefeeding) and intraperitoneal injection of haloperidol were examined on multiple behavioral measures (i.e., the number of trials completed, percent of correct responses, and reaction time). Resistance to prefeeding depended on the probability of food delivery for the number of trials completed and reaction time. Resistance to haloperidol, on the other hand, was not systematically affected by the probability of food delivery for all dependent measures. PMID:22209910

Dual-mass vibratory rate gyroscope with suppressed translational acceleration response and quadrature-error correction capability

NASA Technical Reports Server (NTRS)

Clark, William A. (Inventor); Juneau, Thor N. (Inventor); Lemkin, Mark A. (Inventor); Roessig, Allen W. (Inventor)

2001-01-01

A microfabricated vibratory rate gyroscope to measure rotation includes two proof-masses mounted in a suspension system anchored to a substrate. The suspension has two principal modes of compliance, one of which is driven into oscillation. The driven oscillation combined with rotation of the substrate about an axis perpendicular to the substrate results in Coriolis acceleration along the other mode of compliance, the sense-mode. The sense-mode is designed to respond to Coriolis accelerationwhile suppressing the response to translational acceleration. This is accomplished using one or more rigid levers connecting the two proof-masses. The lever allows the proof-masses to move in opposite directions in response to Coriolis acceleration. The invention includes a means for canceling errors, termed quadrature error, due to imperfections in implementation of the sensor. Quadrature-error cancellation utilizes electrostatic forces to cancel out undesired sense-axis motion in phase with drive-mode position.

End effector of the Discovery's RMS with tools moves toward Syncom-IV

NASA Image and Video Library

1985-04-17

51D-44-046 (17 April 1985) --- The Space Shuttle Discovery's Remote Manipulator System (RMS) arm and two specially designed extensions move toward the troubled Syncom-IV (LEASAT) communications satellite during a station keeping mode of the two spacecraft in Earth orbit. Inside the Shuttle's cabin, astronaut Rhea Seddon, 51D mission specialist, controlled the Canadian-built arm in an attempt to move an external lever on the satellite. Crewmembers learned of the satellite's problems shortly after it was deployed from the cargo bay on April 13, 1985. The arm achieved physical contact with the lever as planned. However, the satellite did not respond to the contact as hoped. A 70mm handheld Hassellblad camera, aimed through Discovery's windows, recorded this frame -- one of the first to be released to news media following return of the seven-member crew on April 17, 1985.

Making the Sour Sweet? Upcoming Food-Pellet Reinforcement Produces Positive Induction When Rats Press a Lever for Unsweetened Lemon Juice

ERIC Educational Resources Information Center

Weatherly, Jeffrey N.; Nurnberger, Jeri T.; Austin, David P.; Wright, Carol L.

2006-01-01

Research has suggested that rats increase their response rate for a low-valued reinforcer when a high-valued reinforcer will soon be available (i.e., positive induction) because the value of the low-valued substance has increased. The present study tested if such a procedure could be used to increase rats' responding for a non-reinforcing food.…

Disinhibition by propranolol and chlordiazepoxide of nonrewarded lever-pressing in the rat is unaffected by dorsal noradrenergic bundle lesion.

PubMed

Salmon, P; Tsaltas, E; Gray, J A

1989-03-01

Ten male Sprague-Dawley rats received 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle and 10 others underwent control operations. The lesion depleted levels of noradrenaline in the hippocampus to 2% of those in the controls. All rats were then trained for 16 sessions to lever-press in a Skinner box on a variable interval 18 sec schedule of food-reinforcement, then for 42 days on a successive discrimination between periods of variable interval (VI 18 sec) food-reinforcement and periods of extinction. This report describes the effects of chlordiazepoxide (CDP; 5 mg/kg) and propranolol (5 and 10 mg/kg) injected intraperitoneally in both groups on modified ABBA designs after this training. Both drugs increased the response rates in extinction periods. The effect of propranolol was similar at each dose and smaller than that of CDP. Although CDP and propranolol (5 mg/kg) increased variable interval response rates also, this could not account for the effect on extinction response rates. Responding did not differ between the lesioned and control animals and the effects of drugs were similar in each group. It is unlikely that CDP or propranolol release nonrewarded responding by disrupting transmission in the dorsal noradrenergic bundle.

Reducing effect of a combination of Phaseolus vulgaris and Cynara scolymus extracts on operant self-administration of a chocolate-flavoured beverage in rats.

PubMed

Zaru, Alessandro; Maccioni, Paola; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo

2013-06-01

Treatment with a rational combination of standardized extracts of Phaseolus vulgaris and Cynara scolymus reduced food intake and glycemia in rats. The present study was designed to assess the effect of this extract combination and of each single extract in an experimental model of food craving, made up of rats displaying exaggerated seeking and taking behaviors for a chocolate-flavoured beverage. After training to lever-respond for the chocolate-flavoured beverage, rats were treated with vehicle, Phaseolus vulgaris extract alone (200 mg/kg), Cynara scolymus extract alone (400 mg/kg), or combination of Phaseolus vulgaris (200 mg/kg) and Cynara scolymus (400 mg/kg) extracts. The Phaseolus vulgaris extract and the extract combination exerted similar and substantial decrements in the number of lever-responses and amount of self-administered chocolate-flavoured beverage; conversely, the Cynara scolymus extract was totally ineffective. These results suggest that (i) the capacity of the extract combination to reduce the self-administration of the chocolate-flavoured beverage entirely relied on the Phaseolus vulgaris extract, (ii) Phaseolus vulgaris extract may interfere with the mechanisms regulating food-related addictive-like behaviors, and (iii) combinations of Phaseolus vulgaris and Cynara scolymus extracts may possess a broad spectrum of activities, from treatment of metabolic syndrome to overweight, obesity, and possibly food-related addictive disorders. Copyright © 2012 John Wiley & Sons, Ltd.

Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor.

PubMed

Bryce, Courtney A; Floresco, Stan B

2016-07-01

Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression.

Perturbations in Effort-Related Decision-Making Driven by Acute Stress and Corticotropin-Releasing Factor

PubMed Central

Bryce, Courtney A; Floresco, Stan B

2016-01-01

Acute stress activates numerous systems in a coordinated effort to promote homeostasis, and can exert differential effects on mnemonic and cognitive functions depending on a myriad of factors. Stress can alter different forms of cost/benefit decision-making, yet the mechanisms that drive these effects, remain unclear. In the present study, we probed how corticotropin-releasing factor (CRF) may contribute to stress-induced alterations in cost/benefit decision-making, using an task where well-trained rats chose between a low effort/low reward lever (LR; two pellets) and a high effort/high reward lever (HR; four pellets), with the effort requirement increasing over a session (2, 5, 10, and 20 presses). One-hour restraint stress markedly reduced preference for the HR option, but this effect was attenuated by infusions of the CRF antagonist, alpha-helical CRF. Conversely, central CRF infusion mimicked the effect of stress on decision-making, as well as increased decision latencies and reduced response vigor. CRF infusions did not alter preference for larger vs smaller rewards, but did reduce responding for food delivered on a progressive ratio, suggesting that these treatments may amplify perceived effort costs that may be required to obtain rewards. CRF infusions into the ventral tegmental area recapitulated the effect of central CRF treatment and restraint on choice behavior, suggesting that these effects may be mediated by perturbations in dopamine transmission. These findings highlight the involvement of CRF in regulating effort-related decisions and suggest that increased CRF activity may contribute to motivational impairments and abnormal decision-making associated with stress-related psychiatric disorders such as depression. PMID:26830960

Examining the Reinforcement-Enhancement Effects of Phencyclidine and Its Interactions with Nicotine on Lever-Pressing for a Visual Stimulus

PubMed Central

Swalve, Natashia; Barrett, Scott T.; Bevins, Rick A.; Li, Ming

2015-01-01

Nicotine is a widely-abused drug, yet its primary reinforcing effect does not seem potent as other stimulants such as cocaine. Recent research on the contributing factors toward chronic use of nicotine-containing products has implicated the role of reinforcement-enhancing effects of nicotine. The present study investigates whether phencyclidine (PCP) may also possess a reinforcement-enhancement effect and how this may interact with the reinforcement-enhancement effect of nicotine. PCP was tested for two reasons: 1) it produces discrepant results on overall reward, similar to that seen with nicotine and 2) it may elucidate how other compounds may interact with the reinforcement-enhancement of nicotine. Adult male Sprague-Dawley rats were trained to lever press for brief visual stimulus presentations under fixed-ratio (FR) schedules of reinforcement and then were tested with nicotine (0.2 or 0.4 mg/kg) and/or PCP (2.0 mg/kg) over six increasing FR values. A selective increase in active lever-pressing for the visual stimulus with drug treatment was considered evidence of a reinforcement-enhancement effect. PCP and nicotine separately increased active lever pressing for a visual stimulus in a dose-dependent manner and across the different FR schedules. The addition of PCP to nicotine did not increase lever-pressing for the visual stimulus, possibly due to a ceiling effect. The effect of PCP may be driven largely by its locomotor stimulant effects, whereas the effect of nicotine was independent of locomotor stimulation. This dissociation emphasizes that distinct pharmacological properties contribute to the reinforcement-enhancement effects of substances. PMID:26026783

Phencyclidine retards autoshaping at a dose which does not suppress the required response.

PubMed

Coveney, J R; Sparber, S B

1982-06-01

Four groups of five food-deprived hooded Long-Evans rats were injected subcutaneously with saline (vehicle) or 2, 4 or 8 mg phencyclidine (PCP) hydrochloride/kg fifteen minutes before being placed for the first time into operant chambers modified to detect exploratory behaviors. Rearing was found to be more sensitive to disruption by phencyclidine than was unconditioned level touching (a measure of floor-level exploratory activities). In an autoshaping session immediately following, the group of animals given the low dose of PCP made as many lever-touch responses as the group given saline, but consumed fewer of the food pellets delivered. In addition, none of the animals in the low-dose group showed within-session shortening of the latency to respond which was observed in four of five control animals. The two other groups given higher doses of PCP demonstrated dose-related decrements in responding as well as a reduction in food pellet consumption during the first session of autoshaping. Over the next two daily autoshaping sessions, performance improved in those groups initially suppressed. Performance converged in all group by the third autoshaping session.

Goal- and signal-directed incentive: conditioned approach, seeking, and consumption established with unsweetened alcohol in rats.

PubMed

Krank, Marvin D; O'Neill, Susan; Squarey, Kyna; Jacob, Jackie

2008-02-01

Many theories of addictive behavior propose that cues signaling drug administration influence the likelihood of drug-taking and drug-seeking behavior. We investigated the behavioral impact of cues associated with unsweetened ethanol and their interaction with responding maintained by ethanol self-administration. Our goal was to establish the influence of such cues on ethanol seeking. The experiment used a matching contingency and saccharin-fading procedure to establish equal levels of responding to two spatially distinct levers using unsweetened 10% ethanol solution. After ethanol self-administration was established, a brief cue light located alternately over each lever location was either paired or unpaired (control) with the opportunity to consume the same ethanol solution. Finally, self-administration was re-established, and the effect of the cue was measured in a transfer design. The reaction to lights paired with the opportunity to ingest unsweetened ethanol had three main effects: (1) induction of operant behavior reinforced by ethanol, (2) stimulation of ethanol-seeking behavior (drinker entries), and (3) cue-directed approach and contact behavior (i.e. autoshaping or sign-tracking). Cue-directed behavior to the light interacted with choice behavior in a manner predicted by the location of the cue light, enhancing responding only when the approach response did not interfere with the operant response. These findings replicate and extend the effects of Pavlovian conditioning on ethanol-seeking and support-conditioned incentive theories of addictive behavior. Signals for ethanol influence spatial choice behavior and may be relevant to attentional bias shown to alcohol-associated stimuli in humans.

Effects of GABA(B) receptor agents on cocaine priming, discrete contextual cue and food induced relapses.

PubMed

Filip, Małgorzata; Frankowska, Małgorzata

2007-10-01

In the present study we investigated the effects of the GABA(B) receptor antagonist (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), the agonists baclofen and 3-aminopropyl(methyl)phosphinic acid (SKF 97541), and the allosteric positive modulator 3,5-bis(1,1-dimethylethyl)-4-hydroxy-beta,beta-dimethylbenzenepropanol (CGP 7930) on cocaine seeking behavior. The effects of the above drugs on the reinstatement of responding induced by natural reinforcer (food) were also studied. Male Wistar rats were trained to self-administer either cocaine (0.5 mg/kg/infusion) or food (sweet milk) and responding on the reinforcer-paired lever was extinguished. Reinstatement of responding was induced by a noncontingent presentation of the self-administered reinforcer (10 mg/kg cocaine, i.p.), a discrete contextual cue, or a contingent presentation of food. SCH 50911 (3-10 mg/kg) dose-dependently attenuated responding on the previously cocaine-paired lever during both reinstatement conditions, with slightly greater efficacy at reducing conditioned cue reinstatement. At the same time, it failed to alter reinstatement of food-seeking behavior. Baclofen (1.25-5 mg/kg) and SKF 97541 (0.03-0.3 mg/kg) attenuated cocaine- or food-seeking behavior; the effect of the drug appeared more effective for cocaine-seeking than food-seeking. CGP 7930 (10-30 mg/kg) reduced cocaine seeking without affecting food-induced reinstatement on reward seeking. Our results indicate that tonic activation of GABA(B) receptors is required for cocaine seeking behavior in rats. Moreover, the GABA(B) receptor antagonist SCH 50911 was effective in reducing relapse to cocaine at doses that failed to alter reinstatement of food-seeking behavior (present study), basal locomotor activity, cocaine and food self-administration (Filip et al., submitted for publication), suggesting its selective effects on motivated drug-seeking behavior. The potent inhibitory responses on cocaine seeking behavior were also seen following the GABA(B) receptor agonists or the allosteric positive modulator, however, doses of baclofen and SKF 97541 that inhibited cocaine-seeking were only threefold lower of those that inhibited food-seeking. In addition, the direct GABA(B) receptor agonists and the allosteric positive modulator cause decreases in cocaine or food self-administration (Filip et al., submitted for publication), indicating their nonspecific effects on relapse to drug-seeking and drug-taking behavior. In conclusion, the GABA(B) receptor antagonist SCH 50911 seems to be viable treatment for reducing cocaine craving and preventing relapse, while the GABA(B) receptor allosteric positive modulator CGP 7930 may hold the highest promise for attenuating cue-evoked relapses to cocaine as well as the direct rewarding properties of cocaine.

Examining the reinforcement-enhancement effects of phencyclidine and its interactions with nicotine on lever-pressing for a visual stimulus.

PubMed

Swalve, Natashia; Barrett, Scott T; Bevins, Rick A; Li, Ming

2015-09-15

Nicotine is a widely-abused drug, yet its primary reinforcing effect does not seem potent as other stimulants such as cocaine. Recent research on the contributing factors toward chronic use of nicotine-containing products has implicated the role of reinforcement-enhancing effects of nicotine. The present study investigates whether phencyclidine (PCP) may also possess a reinforcement-enhancement effect and how this may interact with the reinforcement-enhancement effect of nicotine. PCP was tested for two reasons: (1) it produces discrepant results on overall reward, similar to that seen with nicotine and (2) it may elucidate how other compounds may interact with the reinforcement-enhancement of nicotine. Adult male Sprague-Dawley rats were trained to lever press for brief visual stimulus presentations under fixed-ratio (FR) schedules of reinforcement and then were tested with nicotine (0.2 or 0.4 mg/kg) and/or PCP (2.0mg/kg) over six increasing FR values. A selective increase in active lever-pressing for the visual stimulus with drug treatment was considered evidence of a reinforcement-enhancement effect. PCP and nicotine separately increased active lever pressing for a visual stimulus in a dose-dependent manner and across the different FR schedules. The addition of PCP to nicotine did not increase lever-pressing for the visual stimulus, possibly due to a ceiling effect. The effect of PCP may be driven largely by its locomotor stimulant effects, whereas the effect of nicotine was independent of locomotor stimulation. This dissociation emphasizes that distinct pharmacological properties contribute to the reinforcement-enhancement effects of substances. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of Distant Green Space on Physical Activity in Sydney, Australia.

PubMed

Chong, Shanley; Byun, Roy; Mazumdar, Soumya; Bauman, Adrian; Jalaludin, Bin

2017-01-01

The aim was to investigate the association between distant green space and physical activity modified by local green space. Information about physical activity, demographic and socioeconomic background at the individual level was extracted from the New South Wales Population Health Survey. The proportion of a postcode that was parkland was used as a proxy measure for access to parklands and was calculated for each individual. There was a significant relationship between distant green space and engaging in moderate-to-vigorous physical activity (MVPA) at least once a week. No significant relationship was found between adequate physical activity and distant green space. No significant relationships were found between adequate physical activity, engaging in MVPA, and local green space. However, if respondents lived in greater local green space (≥25%), there was a significant relationship between engaging in MVPA at least once a week and distance green space of ≥20%. This study highlights the important effect of distant green space on physical activity. Our findings also suggest that moderate size of local green space together with moderate size of distant green space are important levers for participation of physical activity.

Stereotypes for lever-tap operation.

PubMed

Chan, Alan H S; Tsang, Steve N H; Hoffmann, Errol R

2016-04-15

Lever-operated taps have become more popular and are commonly used in operating theatres, food preparation areas and where users have poor strength; however, there is very little data available for user expectations on tap operation. Thus, an experiment on dual lever-operated water tap (faucets) was conducted with the aim of for providing information for improved design. This study aims to compare different lever-tap designs and their stereotypes adopted by the end-user to operate them also to verify the stereotypes for increasing or decreasing the water flow. 240 participants were requested to rotate the lever tap to indicate direction for increasing and decreasing water flow with simulated hardware, using actual taps placed at the top of a simulated washbasin. Nine initial positions of the lever were used for increasing and decreasing flows, ranging from the ends of both levers facing outward from the bowl center to the ends of both levers facing inward. All levers operated in the horizontal plane. Strong stereotypes (greater than 80%) for several initial lever orientations were found for increasing water flow, especially when the initial lever end positions were facing outwards. However, for different initial positions at which participants were told that the water was flowing and the flow was to be decreased, no strong stereotypes existed. The stereotypes for increasing water flow of dual-lever taps were strong, whereas those for decreasing water flow were weak and hence the stereotype reversibility was also weak. In terms of user expectations, lever taps do not show any great advantage over cross-taps in terms of operator expectations for increasing and decreasing water flow.

The effects of differing response-force requirements on fixed-ratio responding of rats.

PubMed Central

Alling, K; Poling, A

1995-01-01

Rats were exposed to two-component multiple schedules of food delivery. In the first experiment, 15 responses were required to produce food in both components. A downward force of 0.25 N (25 g) was always required to operate the response lever in one component. In the other, the required force was 0.25, 0.50, 1.00, or 2.00 N (25, 50, 100, or 200 g). In the second experiment, 0.25 N of force operated the lever in one component, but in the other, the force requirement for five consecutive responses at the beginning, middle, or end of each ratio was increased from 0.25 to 2.00 N. In the third experiment, the number of responses required to produce food was reduced from 15 to 5, and then to 1. Again, the effects of altering response force from 0.25 to 2.00 N were examined. In general, as response force increased in all experiments, mean response rates decreased and mean interresponse times increased. PMID:7751836

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

PubMed Central

García-Fuster, M. Julia; Parsegian, Aram; Watson, Stanley J.; Akil, Huda; Flagel, Shelly B.

2018-01-01

Rationale Environmental challenges during adolescence, such as drug exposure, can cause enduring behavioral and molecular changes that contribute to life-long maladaptive behaviors, including addiction. Selectively bred high-responder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-term impact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are considered “addiction-prone”, whereas bLR rats are “addiction-resilient”, at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to “sign-track”. Objectives We utilized bHR and bLR rats to determine whether adolescent cocaine exposure can alter their inborn behavioral and neurobiological profiles, with a specific focus on Pavlovian conditioned approach behavior (i.e. sign- vs. goal-tracking) and hippocampal neurogenesis. Methods bHR and bLR rats were administered cocaine (15 mg/kg) or saline for 7 days during adolescence (postnatal day, PND 33–39) and subsequently tested for Pavlovian conditioned approach behavior in adulthood (PND 62–75), wherein an illuminated lever (conditioned stimulus) was followed by the response-independent delivery of a food pellet (unconditioned stimulus). Behaviors directed towards the lever and the food cup were recorded as sign- and goal-tracking, respectively. Hippocampal cell genesis was evaluated on PND 77 by immunohistochemistry. Results Adolescent cocaine exposure impaired hippocampal cell genesis (proliferation and survival) and enhanced the inherent propensity to goal-track in adult bLR, but not bHR, rats. Conclusions Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats. PMID:28210781

Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily.

PubMed

Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy; McMahon, Lance R

2016-12-01

Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg -1 base weight) from saline. One group received additional nicotine treatment post-session (1.78 mg·kg -1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Daily repeated nicotine treatment produced a time-related increase in saliva cotinine. There was no significant difference in the ED 50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro-β-erythroidine did not. Midazolam produced 0% nicotine-lever responding. The nAChR agonists epibatidine, RTI-36, cytisine and varenicline produced >96% nicotine-lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine-like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. © 2016 The British Pharmacological Society.

Attenuated nicotine‐like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily

PubMed Central

Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy

2016-01-01

Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg−1 base weight) from saline. One group received additional nicotine treatment post‐session (1.78 mg·kg−1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro‐β‐erythroidine did not. Midazolam produced 0% nicotine‐lever responding. The nAChR agonists epibatidine, RTI‐36, cytisine and varenicline produced >96% nicotine‐lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine‐like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Conclusion and Implications Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID:27667659

Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys

PubMed Central

Maguire, David R; Gerak, Lisa R; France, Charles P

2015-01-01

Opioid abusers discount delayed reinforcers more rapidly than non-users; however, it is unclear whether chronic drug administration or its discontinuation impact discounting. This study examined daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Responding on one lever delivered 1 food pellet immediately; responding on another lever delivered 2 food pellets either immediately or after a delay (30–120 sec) that increased within the session. Monkeys (n=3) responded for the large reinforcer when both reinforcers were delivered immediately and more for the smaller, immediately available reinforcer as delay to delivery of the large reinforcer increased. When administered acutely, morphine (0.032–5.6 mg/kg) increased trial omissions and had variable effects on choice, with small doses decreasing and large doses increasing choice of the large delayed reinforcer. Chronic morphine administration (0.1 mg/kg/day to 3.2 mg/kg twice daily) reduced choice of the large delayed reinforcer in two monkeys while increasing choice in a third monkey. Despite the development of tolerance to some effects (i.e., rightward shifts in dose-effect curves for the number of trials omitted) and evidence of mild opioid dependence (e.g., decrease in the number of trials completed as well as body weight), discontinuation of treatment did not appear to systematically impact discounting. Overall, these results suggest that repeated opioid administration causes persistent effects on choice under a delay discounting procedure; however, differences in the direction of effect among individuals suggest factors other than, or in addition to, changes in discounting might play a role. PMID:26397762

14. INTERIOR OF MAIN DECKNOTE LEVERS FROM CEILING CONTROLLED BY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. INTERIOR OF MAIN DECK--NOTE LEVERS FROM CEILING CONTROLLED BY OPERATOR. LEFT HAND LEVER CONTROLLED THROTTLE, RIGHT HAND LEVER CONTROLLED SHOT GUN SWINGER. - Dredge CINCINNATI, Docked on Ohio River at foot of Lighthill Street, Pittsburgh, Allegheny County, PA

49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical interlocking machine, locking between electric and mechanical levers shall be maintained so that mechanical...

Response-food delay gradients for lever pressing and schedule-induced licking in rats.

PubMed

Pellón, Ricardo; Pérez-Padilla, Angeles

2013-06-01

Eight food-deprived Wistar rats developed stable patterns of lever pressing and licking when exposed to a fixed-time 30-s schedule of food pellet presentation. The rats were trained to lever press by presenting the lever 10 s before the programmed food delivery, with the food pellet being delivered immediately upon a lever press. The operant contingency was then removed and the lever was inserted through the entire interfood interval, being withdrawn with food delivery and reinserted 2 s later. On successive phases of the study, a protective contingency postponed food delivery if responses (lever presses or licks) occurred within the last 1, 2, 5, 10, 20, or 25 s of the interfood interval. Lever pressing was reduced at much shorter response-food delays than those that reduced licking. These results demonstrate that reinforcement contributes to the maintenance of different response patterns on periodic schedules, and that different responses are differentially sensitive to delays.

A comparison of Lewis and Fischer rat strains on autoshaping (sign-tracking), discrimination reversal learning and negative auto-maintenance.

PubMed

Kearns, David N; Gomez-Serrano, Maria A; Weiss, Stanley J; Riley, Anthony L

2006-05-15

Lewis (LEW) and Fischer (F344) rat strains differ on a number of physiological characteristics, such as hypothalamic-pituitary-adrenal (HPA) axis activity, as well as on behavioral tasks, including those that measure impulsivity and drug reward. Since autoshaping, the phenomenon where animals approach and contact reward-paired conditioned stimuli, has been linked to HPA axis functioning, impulsivity and drug taking, the present study compared LEW and F344 rats on the rate of acquisition and performance of the autoshaping response. Rats were trained on an autoshaping procedure where insertions of one retractable lever (CS(+)) were paired response-independently with food, while insertions of another lever (CS(-)) were not paired with food. LEW rats acquired the autoshaping response more rapidly and also performed the autoshaping response at a higher rate than F344 rats. No differences between the strains were observed when rats were trained on a discrimination reversal where the CS(+) and CS(-) levers were reversed or during a negative auto-maintenance phase where CS(+) lever contacts cancelled food delivery. Potential physiological mechanisms that might mediate the present results, including strain differences in HPA axis and monoamine neurotransmitter activity, are discussed. The finding that LEW (as compared to F344 rats) more readily acquire autoshaping and perform more responses is consistent with research indicating that LEW rats behave more impulsively and more readily self-administer drugs of abuse.

Orbitofrontal Cortical Neurons Encode Expectation-Driven Initiation of Reward-Seeking

PubMed Central

Aston-Jones, Gary

2014-01-01

Adaptive execution and inhibition of behavior are guided by the activity of neuronal populations across multiple frontal cortical areas. The rodent medial prefrontal cortex has been well studied with respect to these behaviors, influencing behavioral execution/inhibition based on context. Other frontal regions, in particular the orbitofrontal cortex (OFC), are critical in directing behavior to obtain rewards, but the relationship between OFC neuronal activity and response execution or inhibition has been poorly characterized. In particular, little is known about OFC with respect to extinction learning, an important example of context-guided response inhibition. Here, we recorded the activity of OFC neurons while rats performed a discriminative-stimulus (DS)-driven sucrose-seeking task followed by multiple days of extinction of the DS. OFC neuronal activity was maximally responsive (1) to reward-predicting stimuli (RS) that triggered a lever press (i.e., lever-response initiation) and (2) during reward-well approach in pursuit of sucrose (i.e., well-response initiation). RS presentation that was not followed by a lever press or RS presentation during extinction produced weak activation, as did nonrewarded stimulus (NS) presentation regardless of response (press or withhold) or session (DS-sucrose or extinction). Activity related to nonrewarded well entry was minor, and activity was significantly inhibited during reward consumption. Finally, OFC neuronal activity switched selectivity to track rewarded behaviors when the RS/NS contingencies were reversed. Thus, rather than signaling variables related to extinction or response inhibition, activity in OFC was strongest at the initiation of multiple components of reward-seeking behavior, most prominently when valid reward-predicting cues drove these behaviors. PMID:25080585

Evidence for a shared representation of sequential cues that engage sign-tracking.

PubMed

Smedley, Elizabeth B; Smith, Kyle S

2018-06-19

Sign-tracking is a phenomenon whereby cues that predict rewards come to acquire their own motivational value (incentive salience) and attract appetitive behavior. Typically, sign-tracking paradigms have used single auditory, visual, or lever cues presented prior to a reward delivery. Yet, real world examples of events often can be predicted by a sequence of cues. We have shown that animals will sign-track to multiple cues presented in temporal sequence, and with time develop a bias in responding toward a reward distal cue over a reward proximal cue. Further, extinction of responding to the reward proximal cue directly decreases responding to the reward distal cue. One possible explanation of this result is that serial cues become representationally linked with one another. Here we provide further support of this by showing that extinction of responding to a reward distal cue directly reduces responding to a reward proximal cue. We suggest that the incentive salience of one cue can influence the incentive salience of the other cue. Copyright © 2018. Published by Elsevier B.V.

39. CLOSE UP DETAIL OF THE FEEDER AND STAMP CONNECTION. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

39. CLOSE UP DETAIL OF THE FEEDER AND STAMP CONNECTION. THE STAMP AN MORTAR BOX ARE ON THE LEFT AND THE FEEDER WITH ITS FEEDER DISK IS ON THE RIGHT. NOTE THE COLLAR ON THE CENTER STAMP STEM (UPPER LEFT CORNER OF THE IMAGE) THAT ACTIVATES THE LEVER IN THE CENTER OF THE PHOTO. THE COLLAR IS POSITIONED SUCH THAT WHEN THE LEVEL OF THE MATERIAL REACHES A LOW POINT IN THE MORTAR BOX IT PUSHES DOWN ON THE LEVER WHICH IN TURN ACTIVATES THE AUTOMATIC FEEDER DRIVE MECHANISM WHICH THEM DELIVERS ORE INTO THE BACKSIDE OF THE MORTAR BOX. - Standard Gold Mill, East of Bodie Creek, Northeast of Bodie, Bodie, Mono County, CA

The monoamine-oxidase B inhibitor deprenyl increases selection of high-effort activity in rats tested on a progressive ratio/chow feeding choice procedure: Implications for treating motivational dysfunctions.

PubMed

Yohn, Samantha E; Reynolds, Shanika; Tripodi, Giuseppe; Correa, Merce; Salamone, John D

2018-04-16

Motivated behaviors often are characterized by a high degree of behavioral activation and work output, and organisms frequently make effort-related decisions based upon cost/benefit analyses. Moreover, people with depression and other disorders frequently show effort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue. Tasks measuring effort-related choice are being used as animal models of these motivational symptoms. The present studies characterized the ability of the monoamine oxidase -B (MAO-B) inhibitor deprenyl (selegiline) to enhance selection of high-effort lever pressing in rats tested on a concurrent progressive ratio (PROG)/chow feeding choice task. Deprenyl is widely used as an antiparkinsonian drug, but it also has been shown to have antidepressant effects in humans, and to induce antidepressant-like effects in traditional rodent models of depression. Systemic administration of deprenyl (1.5-12.0 mg/kg IP) shifted choice behavior, significantly increasing markers of PROG lever pressing at a moderate dose (6.0 mg/kg), and decreasing chow intake at 6.0 and 12.0 mg/kg. Intracranial injections of deprenyl into nucleus accumbens (2.0 and 4.0 μg) also increased PROG lever pressing and decreased chow intake. Microdialysis studies showed that the dose of deprenyl that was effective at increasing PROG lever pressing (6.0 mg/kg) also significantly elevated extracellular dopamine in nucleus accumbens. Thus, similar to the well-known antidepressant bupropion, deprenyl is capable of increasing selection of high-effort PROG lever pressing at doses that increase extracellular dopamine in nucleus accumbens. These studies have implications for the potential use of MAO-B inhibitors as treatments for the motivational symptoms of depression and Parkinsonism. Copyright © 2018 Elsevier B.V. All rights reserved.

Using clinical governance levers to support change in a cancer care reform.

PubMed

Brault, Isabelle; Denis, Jean-Louis; Sullivan, Terrence James

2015-01-01

Introducing change is a difficult issue facing all health care systems. The use of various clinical governance levers can facilitate change in health care systems. The purpose of this paper is to define clinical governance levers, and to illustrate their use in a large-scale transformation. The empirical analysis deals with the in-depth study of a specific case, which is the organizational model for Ontario's cancer sector. The authors used a qualitative research strategy and drew the data from three sources: semi-structured interviews, analysis of documents, and non-participative observations. From the results, the authors identified three phases and several steps in the reform of cancer services in this province. The authors conclude that a combination of clinical governance levers was used to transform the system. These levers operated at different levels of the system to meet the targeted objectives. To exercise clinical governance, managers need to acquire new competencies. Mobilizing clinical governance levers requires in-depth understanding of the role and scope of clinical governance levers. This study provides a better understanding of clinical governance levers. Clinical governance levers are used to implement an organizational environment that is conducive to developing clinical practice, as well as to act directly on practices to improve quality of care.

Effects of environmental enrichment on extinction and reinstatement of amphetamine self-administration and sucrose-maintained responding.

PubMed

Stairs, Dustin J; Klein, Emily D; Bardo, Michael T

2006-11-01

The current experiments aimed to determine whether differential rearing alters extinction and/or reinstatement of amphetamine self-administration or sucrose-maintained responding. Male Sprague-Dawley rats were raised in either an enriched condition or an isolated condition. Rats were then trained to lever press on a continuous reinforcement schedule across either 15 daily amphetamine self-administration sessions or 15 sucrose-reinforced sessions, followed by 10 sessions of extinction. After the extinction sessions, priming doses of amphetamine (0, 0.25 or 1.0 mg/kg) were administered 15 min before the session, or sucrose (one or 10 pellets) was delivered non-contingently at the beginning of the session. Enriched condition rats showed greater extinction for amphetamine and sucrose-maintained responding than isolated condition rats. When primed with amphetamine, isolated condition rats reinstated responding following 0.25 mg/kg of amphetamine, whereas enriched condition rats only reinstated responding after 1.0 mg/kg of amphetamine. Isolated condition rats failed to reinstate responding following sucrose delivery, while enriched condition rats reinstated responding following the delivery of 10 sucrose pellets. These results indicate that environmental enrichment enhanced the extinction of both amphetamine and sucrose-maintained responding. Environmental enrichment also raised the reinstatement threshold specific to the amphetamine prime, suggesting a reduction in the incentive motivational effect of amphetamine.

Lightweight Seat Lever Operation Characteristics

NASA Technical Reports Server (NTRS)

Rajulu, Sudhakar

1999-01-01

In 1999, a Shuttle crew member was unable to operate the backrest lever for the lightweight seat in microgravity. It is essential that crew members can adjust this backrest lever, which is titled forward during launch and then moved backward upon reaching orbit. This adjustment is needed to cushion the crew members during an inadvertent crash landing situation. JSCs Anthropometry and Biomechanics Facility (ABF) performed an evaluation of the seat controls and provided recommendations on whether the seat lever positions and operations should be modified. The original Shuttle seats were replaced with new lightweight seats whose controls were moved, with one control at the front and the other at the back. The ABF designed a 12-person experiment to investigate the amount of pull force exerted by suited subjects, when controls were placed in the front and back of the lightweight seat. Each subject was asked to perform the pull test at least three times for each combination of lever position and suit pressure conditions. The results showed that, in general, the subjects were able to pull on the lever at the back position with only about half the amount of force that they were able to exert on the lever at the front position. In addition, the results also showed that subjects wearing the pressurized suit were unable to reach the seat lever when it was located at the back. The pull forces on the front lever diminished about 50% when subjects wore pressurized suits. Based on these results from this study, it was recommended that the levers should not be located in the back position. Further investigation is needed to determine whether the levers at the front of the seat could be modified or adjusted to increase the leverage for crew members wearing pressurized launch/escape suits.

77 FR 68055 - Airworthiness Directives; Bell Helicopter Textron Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

... collective lever for a crack, and if there is a crack, before further flight, replacing the collective lever.... The actions are intended to detect a crack in the collective lever, which could lead to failure of the... cracks with a 10X or higher power magnifying glass. If there is a crack in the collective lever paint...

Five Policy Levers To Meet The Value Challenge In Cancer Care.

PubMed

Callahan, Ryan; Darzi, Ara

2015-09-01

The burden of cancer on public finances is a serious concern for policy makers. More people are developing cancer, and as standards of care have risen, more are surviving and requiring longer-term care. Precision medicine promises better outcomes but demands commensurately higher payments for care. As both incidence and per case costs rise, we suggest that the task of expanding access to high-quality cancer care poses a "value challenge" that policies in many countries are inadequate to meet. Policy makers should respond with a new approach. We explore questions that policy makers will need to consider regarding objectives, barriers, and levers for policy development. We use transparency and accountability as cornerstones of a new approach to promote value-based decision making. Although barriers to advancing this agenda are formidable, we recommend that governments define common standards for value-based accounting; serve as information brokers for evidence development; pioneer value-based procurement of goods and services; engage in deliberative democracy in cancer care; and educate communities to facilitate knowledge sharing between communities of patients, their caretakers, and researchers. Project HOPE—The People-to-People Health Foundation, Inc.

Constraining response output on conjunctive fixed-ratio 1 fixed-time reinforcement schedules: Effects on the postreinforcement pause.

PubMed

Lopez, F; Pereira, C

1985-03-01

Two experiments used response-restriction procedures in order to test the independence of the factors determining response rate and the factors determining the size of the postreinforcement pause on interval schedules. Responding was restricted by response-produced blackout or by retracting the lever. In Experiment 1 with a Conjunctive FR 1 FT schedule, the blackout procedure reduced the postreinforcement pause more than the lever-retraction procedure did, and both procedures produced shorter pauses than did the schedule without response restriction. In Experiment 2 the interreinforcement interval was also manipulated, and the size of the pause was an increasing function of the interreinforcement interval, but the rate of increase was lower than that produced by fixed interval schedules of comparable interval durations. The assumption of functional independence of the postreinforcement pause and terminal rate in fixed interval schedules is questioned since data suggest that pause reductions resulted from constraining variation in response number compared to equivalent periodic schedules in which response number was allowed to vary. Copyright © 1985. Published by Elsevier B.V.

Health Information Exchange Readiness for Demonstrating Return on Investment and Quality of Care.

PubMed

Khurshid, Anjum; Diana, Mark L; Jain, Rahul

2015-01-01

To study the extent to which community health information exchanges (HIEs) deliver and measure return on investment (ROI) and improvements in the quality of care. We surveyed operational HIEs for their characteristics, information domains, impact on quality of care, and ROI. A 60 percent response rate was achieved. Two-thirds of respondents agreed that community HIEs demonstrated a positive ROI, while one-third had no opinion or disagreed. One-fourth or fewer respondents reported using various metrics to calculate ROI. Most respondents agreed that HIEs improve the quality of care, though several were not sure and were awaiting further evidence. Most respondents indicated that they did not deliver reports on quality measures (76 percent) and that data were not being used to measure quality performance of participating providers (73 percent). Respondents from most HIEs believe that the HIEs are demonstrating a positive ROI; however, a minority of them indicated they had used or will use specific metrics to calculate ROI. HIE representatives overwhelmingly reported that they believe the HIE activities improve the quality of healthcare delivered, but only a few are using data to evaluate provider performance or generate reports on quality measures. This study demonstrates the challenge faced by policy makers and healthcare organizations that are investing millions of dollars in HIEs that are believed to improve health outcomes and increase efficiency, but still need more time to develop the evidence to confirm that belief. Our study shows that calculating ROI for HIEs or their impact on quality of care remains a secondary priority for most HIEs. This finding raises serious questions for the sustained support of HIEs, both financially and as a policy lever, given the end of Health Information Technology for Economic and Clinical Health (HITECH) Act funding.

Synergistic interaction between baclofen administration into the median raphe nucleus and inconsequential visual stimuli on investigatory behavior of rats

PubMed Central

Vollrath-Smith, Fiori R.; Shin, Rick

2011-01-01

Rationale Noncontingent administration of amphetamine into the ventral striatum or systemic nicotine increases responses rewarded by inconsequential visual stimuli. When these drugs are contingently administered, rats learn to self-administer them. We recently found that rats self-administer the GABAB receptor agonist baclofen into the median (MR) or dorsal (DR) raphe nuclei. Objectives We examined whether noncontingent administration of baclofen into the MR or DR increases rats’ investigatory behavior rewarded by a flash of light. Results Contingent presentations of a flash of light slightly increased lever presses. Whereas noncontingent administration of baclofen into the MR or DR did not reliably increase lever presses in the absence of visual stimulus reward, the same manipulation markedly increased lever presses rewarded by the visual stimulus. Heightened locomotor activity induced by intraperitoneal injections of amphetamine (3 mg/kg) failed to concur with increased lever pressing for the visual stimulus. These results indicate that the observed enhancement of visual stimulus seeking is distinct from an enhancement of general locomotor activity. Visual stimulus seeking decreased when baclofen was co-administered with the GABAB receptor antagonist, SCH 50911, confirming the involvement of local GABAB receptors. Seeking for visual stimulus also abated when baclofen administration was preceded by intraperitoneal injections of the dopamine antagonist, SCH 23390 (0.025 mg/kg), suggesting enhanced visual stimulus seeking depends on intact dopamine signals. Conclusions Baclofen administration into the MR or DR increased investigatory behavior induced by visual stimuli. Stimulation of GABAB receptors in the MR and DR appears to disinhibit the motivational process involving stimulus–approach responses. PMID:21904820

A new criterion for acquisition of nicotine self-administration in rats.

PubMed

Peartree, Natalie A; Sanabria, Federico; Thiel, Kenneth J; Weber, Suzanne M; Cheung, Timothy H C; Neisewander, Janet L

2012-07-01

Acquisition of nicotine self-administration in rodents is relatively difficult to establish and measures of acquisition rate are sometimes confounded by manipulations used to facilitate the process. This study examined acquisition of nicotine self-administration without such manipulations and used mathematical modeling to define the criterion for acquisition. Rats were given 20 daily 2-h sessions occurring 6 days/week in chambers equipped with active and inactive levers. Each active lever press resulted in nicotine reinforcement (0-0.06 mg/kg, IV) and retraction of both levers for a 20-s time out, whereas inactive lever presses had no consequences. Acquisition was defined for individual rats by the higher likelihood of reinforcers obtained across sessions fitting a logistic over a constant function according to the corrected Akaike Information Criterion (AICc). For rats that acquired self-administration, an AICc-based multi-model comparison demonstrated that the asymptote (highest number of reinforcers/session) and mid-point of the acquisition curve (h; the number of sessions necessary to reach half the asymptote) varied by nicotine dose, with both exhibiting a negative relationship (the higher the dose, the lower number of reinforcers and the lower h). The modeling approach used in this study provides a way of defining acquisition of nicotine self-administration that takes advantage of all data from individual subjects and the procedure used is sensitive to dose differences in the absence of manipulations that influence acquisition (e.g., food restriction, prior food reinforcement, conditioned reinforcers). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Adolescent nicotine exposure sensitizes cue-induced reinstatement of cocaine seeking in rats bred for high and low saccharin intake.

PubMed

Anker, Justin J; Carroll, Marilyn E

2011-10-01

Environmental factors such as early drug exposure influence drug abuse vulnerability, and evidence also suggests that drug abuse is highly heritable. The purpose of the present study was to determine whether environmental and genetic factors interact to produce additive drug abuse vulnerability. An animal model of relapse was used to examine the effects of adolescent nicotine exposure on adult cocaine seeking in rats bred for high (HiS) and low (LoS) saccharin intake. Rats from HiS and LoS progenitor lines received s.c. injections of nicotine for 10 days (postnatal days 22-31). Rats were then allowed to reach adulthood and were trained to lever press for cocaine infusions. During each self-administration session, the house light (HL) was illuminated and each lever press activated a set of lights adjacent to the lever (LL). Following cocaine self-administration, the HL and LL were deactivated, cocaine solutions were replaced with saline, and rats extinguished lever pressing. Subsequently, rats were tested under a multi-component reinstatement procedure consisting of: (1) cue-induced reinstatement with LL alone and the HL presented alone, (2) cocaine-induced reinstatement without LL and HL present, (3) and cocaine-induced reinstatement with LL present. The results indicated that adolescent nicotine exposure sensitized the reinstatement of cocaine seeking during adulthood in HiS (but not LoS) rats when lever pressing resulted in LL cue presentations. In addition, following administration of the cocaine priming injection, rats exposed to nicotine (vs. saline) during adolescence (LoS and HiS) engaged in more cocaine seeking under the cocaine-primed reinstatement condition when lever pressing illuminated the LL. These results suggest that drug abuse vulnerability may be a function of early life exposure to drugs of abuse in addition to genetic influences. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chronic pain impairs cognitive flexibility and engages novel learning strategies in rats.

PubMed

Cowen, Stephen L; Phelps, Caroline E; Navratilova, Edita; McKinzie, David L; Okun, Alec; Husain, Omar; Gleason, Scott D; Witkin, Jeffrey M; Porreca, Frank

2018-03-22

Cognitive flexibility, the ability to adapt behavior to changing outcomes, is critical for survival. The prefrontal cortex is a key site of cognitive control and chronic pain is known to lead to significant morphological changes to this brain region. Nevertheless, the effects of chronic pain on cognitive flexibility and learning remain uncertain. We used an instrumental paradigm to assess adaptive learning in an experimental model of chronic pain induced by tight ligation of the spinal nerves L5/6 (SNL model). Naïve, sham-operated, and SNL rats were trained to perform fixed-ratio, variable-ratio, and contingency-shift behaviors for food reward. Although all groups learned an initial lever-reward contingency, learning was slower in SNL animals in a subsequent choice task that reversed reinforcement contingencies. Temporal analysis of lever-press responses across sessions indicated no apparent deficits in memory consolidation or retrieval. However, analysis of learning within sessions revealed that the lever presses of SNL animals occurred in bursts followed by delays. Unexpectedly, the degree of bursting correlated positively with learning. Under a variable-ratio probabilistic task, SNL rats chose a less profitable behavioral strategy compared to naïve and sham-operated animals. Following extinction of behavior for learned preferences, SNL animals reverted to their initially preferred (i.e., less profitable) behavioral choice. Our data suggest, that in the face of uncertainty, chronic pain drives a preference for familiar associations, consistent with reduced cognitive flexibility. The observed burst-like responding may represent a novel learning strategy in animals with chronic pain.

Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine

PubMed Central

Ball, Kevin T.; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan

2015-01-01

Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one’s drug use history. PMID:26241170

The Effects of Lever Arm (Instrument Offset) Error on GRAV-D Airborne Gravity Data

NASA Astrophysics Data System (ADS)

Johnson, J. A.; Youngman, M.; Damiani, T.

2017-12-01

High quality airborne gravity collection with a 2-axis, stabilized platform gravity instrument, such as with a Micro-g LaCoste Turnkey Airborne Gravity System (TAGS), is dependent on the aircraft's ability to maintain "straight and level" flight. However, during flight there is constant rotation about the aircraft's center of gravity. Standard practice is to install the scientific equipment close to the aircraft's estimated center of gravity to minimize the relative rotations with aircraft motion. However, there remain small offsets between the instruments. These distance offsets, the lever arm, are used to define the rigid-body, spatial relationship between the IMU, GPS antenna, and airborne gravimeter within the aircraft body frame. The Gravity for the Redefinition of the American Vertical Datum (GRAV-D) project, which is collecting airborne gravity data across the U.S., uses a commercial software package for coupled IMU-GNSS aircraft positioning. This software incorporates a lever arm correction to calculate a precise position for the airborne gravimeter. The positioning software must do a coordinate transformation to relate each epoch of the coupled GNSS-IMU derived position to the position of the gravimeter within the constantly-rotating aircraft. This transformation requires three inputs: accurate IMU-measured aircraft rotations, GNSS positions, and lever arm distances between instruments. Previous studies show that correcting for the lever arm distances improves gravity results, but no sensitivity tests have been done to investigate how error in the lever arm distances affects the final airborne gravity products. This research investigates the effects of lever arm measurement error on airborne gravity data. GRAV-D lever arms are nominally measured to the cm-level using surveying equipment. "Truth" data sets will be created by processing GRAV-D flight lines with both relatively small lever arms and large lever arms. Then negative and positive incremental errors will be introduced independently in the x, y, and z directions during GPS-IMU processing. Finally, the post-processed gravity data obtained using the erroneous lever arms will be compared to the post-processed truth sets to identify relationships between error in the lever arm measurement and the final gravity product.

Orbital cortex neuronal responses during an odor-based conditioned associative task in rats.

PubMed

Yonemori, M; Nishijo, H; Uwano, T; Tamura, R; Furuta, I; Kawasaki, M; Takashima, Y; Ono, T

2000-01-01

Neuronal activity in the rat orbital cortex during discrimination of various odors [five volatile organic compounds (acetophenone, isoamyl acetate, cyclohexanone, p-cymene and 1,8-cineole), and food- and cosmetic-related odorants (black pepper, cheese, rose and perfume)] and other conditioned sensory stimuli (tones, light and air puff) was recorded and compared with behavioral responses to the same odors (black pepper, cheese, rose and perfume). In a neurophysiological study, the rats were trained to lick a spout that protruded close to its mouth to obtain sucrose or intracranial self-stimulation reward after presentation of conditioned stimuli. Of 150 orbital cortex neurons recorded during the task, 65 responded to one or more types of sensory stimuli. Of these, 73.8% (48/65) responded during presentation of an odor. Although the mean breadth of responsiveness (entropy) of the olfactory neurons based on the responses to five volatile organic compounds and air (control) was rather high (0.795), these stimuli were well discriminated in an odor space resulting from multidimensional scaling using Pearson's correlation coefficients between the stimuli. In a behavioral study, a rat was housed in an equilateral octagonal cage, with free access to food and choice among eight levers, four of which elicited only water (no odor, controls), and four of which elicited both water and one of four odors (black pepper, cheese, rose or perfume). Lever presses for each odor and control were counted. Distributions of these five stimuli (four odors and air) in an odor space derived from the multidimensional scaling using Pearson's correlation coefficients based on behavioral responses were very similar to those based on neuronal responses to the same five stimuli. Furthermore, Pearson's correlation coefficients between the same five stimuli based on the neuronal responses and those based on behavioral responses were significantly correlated. The results demonstrated a pivotal role of the rat orbital cortex in olfactory sensory processing and suggest that the orbital cortex is important in the manifestation of various motivated behaviors of the animals, including odor-guided motivational behaviors (odor preference).

Techniques for establishing schedules with wheel running as reinforcement in rats.

PubMed

Iversen, I H

1993-07-01

In three experiments, access to wheel running was contingent on lever pressing. In each experiment, the duration of access to running was reduced gradually to 4, 5, or 6 s, and the schedule parameters were expanded gradually. The sessions lasted 2 hr. In Experiment 1, a fixed-ratio 20 schedule controlled a typical break-and-run pattern of lever pressing that was maintained throughout the session for 3 rats. In Experiment 2, a fixed-interval schedule of 6 min maintained lever pressing throughout the session for 3 rats, and for 1 rat, the rate of lever pressing was positively accelerated between reinforcements. In Experiment 3, a variable-ratio schedule of 20 or 35 was in effect and maintained lever pressing at a very stable pace throughout the session for 2 of 3 rats; for 1 rat, lever pressing was maintained at an irregular rate. When the session duration was extended to successive 24-hr periods, with food and water accessible in Experiment 3, lever pressing settled into a periodic pattern occurring at a high rate at approximately the same time each day. In each experiment, the rats that developed the highest local rates of running during wheel access also maintained the most stable and highest rates of lever pressing.

Rotational foot placement specifies the lever arm of the ground reaction force during the push-off phase of walking initiation.

PubMed

Erdemir, Ahmet; Piazza, Stephen J

2002-06-01

The lever arm of the ground reaction force (GRF) about the talocrural joint axis is a functionally important indicator of the nature of foot loading. Walking initiation experiments (ten subjects; age, 23-29 years) were completed to demonstrate that rotational foot placement is a possible strategy to specify the lever arm. Externally-rotated foot placement resulted in larger lever arms during push-off. A computer simulation of push-off revealed that a decreased lever arm reduces the plantarflexion moment necessary to maintain a constant forward velocity, while increasing the required plantarflexion velocity. Shortening of the foot thus diminishes the muscular force demand but also requires high muscle fiber shortening velocities that may limit the force generating capacity of plantar flexors. Decreased plantar flexion moment and slow walking previously noted in partial-foot amputees may result from shortened lever arms in this manner.

Economic substitutability of electrical brain stimulation, food, and water.

PubMed Central

Green, L; Rachlin, H

1991-01-01

Concurrent variable-ratio schedules of electrical brain stimulation, food, and water were paired in various combinations as reinforcement of rats' lever presses. Relative prices of the concurrent reinforcers were varied by changing the ratio of the response requirements on the two levers. Economic substitutability, measured by the sensitivity of response ratio to changes in relative price, was highest with brain stimulation reinforcement of presses on both levers and lowest with food reinforcement of presses on one lever and water reinforcement of presses on the other. Substitutability with brain stimulation reinforcement of presses on one lever and either food or water reinforcement for presses on the other was about as high as with brain stimulation for presses on both levers. Electrical brain stimulation for rats may thus serve as an economic substitute for two reinforcers, neither of which is substitutable for the other. PMID:2037823

Dual resolution, vacuum compatible optical mount

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halpin, John Michael

2011-10-04

An optical mount for an optical element includes a mounting plate, a lever arm pivot coupled to mounting plate, and an adjustment plate. The optical mount also includes a flexure pivot mechanically coupling the adjustment plate to the mounting plate and a lever arm. The optical mount further includes a first adjustment device extending from the adjustment plate to make contact with the lever arm at a first contact point. A projection of a line from the first contact point to a pivot point, measured along the lever arm, is a first predetermined distance. The optical mount additionally includes amore » second adjustment device extending from the adjustment plate to make contact with the lever arm at a second contact point. A projection of a line from the second contact point to the pivot point, measured along the lever arm, is a second predetermined distance greater than the first predetermined distance.« less

Self-calibration method of the inner lever-arm parameters for a tri-axis RINS

NASA Astrophysics Data System (ADS)

Song, Tianxiao; Li, Kui; Sui, Jie; Liu, Zengjun; Liu, Juncheng

2017-11-01

A rotational inertial navigation system (RINS) could improve navigation performance by modulating the inertial sensor errors with rotatable gimbals. When an inertial measurement unit (IMU) rotates, the deviations between the accelerometer-sensitive points and the IMU center will lead to an inner lever-arm effect. In this paper, a self-calibration method of the inner lever-arm parameters for a tri-axis RINS is proposed. A novel rotation scheme with variable angular rate rotation is designed to motivate the velocity errors caused by the inner lever-arm effect. By extending all inner lever-arm parameters as filter states, a Kalman filter with velocity errors as measurement is established to achieve the calibration. The accuracy and feasibility of the proposed method are illustrated by both simulations and experiments. The final results indicate that the inner lever-arm effect is significantly restrained after compensation by the calibration results.

Effects of amphetamine on delay discounting in rats depend upon the manner in which delay is varied

PubMed Central

Maguire, David R; Henson, Cedric; France, Charles P

2014-01-01

Whether stimulant drugs like amphetamine increase or decrease choice of larger delayed reinforcers over smaller immediately available reinforcers under delay discounting procedures can depend on several factors, including the order in which delay is presented. This study examined whether the order of delay presentation impacts drug effects on discounting in rats (n=8) trained and tested under an ascending order, a descending order, as well as under a fixed delay condition. Responses on one lever delivered 1 food pellet immediately and responses on the other lever delivered 3 food pellets immediately or after a delay (4–32 s). In Experiment 1, the delay to the larger reinforcer varied within session and the order of delay presentation (ascending or descending) varied across conditions. In Experiment 2, the same delay value was presented in all blocks of the session (i.e., delay was fixed), and delay varied across phases. Under the ascending order of delay, amphetamine (0.32–1.78 mg/kg) increased choice of the larger reinforcer in some rats and decreased choice in others. In the same rats responding under the descending and fixed delay conditions, amphetamine markedly decreased choice of the larger reinforcer even in the component associated with no delay. In some subjects, the effects of amphetamine differed depending on the manner in which delay was presented, indicating that drug-induced changes in performance were due, in part, to mechanisms other than altered sensitivity to reinforcer delay. These results also suggest that a history of responding under both orders of delay presentation can modulate drug effects. PMID:24780379

Premature responding is associated with approach to a food cue in male and female heterogeneous stock rats.

PubMed

King, Christopher P; Palmer, Abraham A; Woods, Leah C Solberg; Hawk, Larry W; Richards, Jerry B; Meyer, Paul J

2016-07-01

Disorders of behavioral regulation, including attention deficit hyperactivity disorder (ADHD) and drug addiction, are in part due to poor inhibitory control, attentional deficits, and hyper-responsivity to reward-associated cues. To determine whether these traits are related, we tested genetically variable male and female heterogeneous stock rats in the choice reaction time (CRT) task and Pavlovian conditioned approach (PavCA). Sex differences in the response to methylphenidate during the CRT were also assessed. In the CRT task, rats were required to withhold responding until one of two lights indicated whether responses into a left or right port would be reinforced with water. Reaction time on correct trials and premature responses were the operational definitions of attention and response inhibition, respectively. Rats were also pretreated with oral methylphenidate (0, 2, 4 mg/kg) during the CRT task to determine whether this drug would improve performance. Subsequently, during PavCA, presentation of an illuminated lever predicted the delivery of a food pellet into a food-cup. Lever-directed approach (sign-tracking) and food-cup approach (goal-tracking) were the primary measures, and rats were categorized as "sign-trackers" and "goal-trackers" using an index based on these measures. Sign-trackers made more premature responses than goal-trackers but showed no differences in reaction time. There were sex differences in both tasks, with females having higher sign-tracking, completing more CRT trials, and making more premature responses after methylphenidate administration. These results indicate that response inhibition is related to reward-cue responsivity, suggesting that these traits are influenced by common genetic factors.

Reinstatement of cocaine seeking induced by drugs, cues, and stress in adolescent and adult rats

PubMed Central

Carroll, Marilyn E.

2010-01-01

Rationale In human and animal studies, adolescence marks a period of increased vulnerability to the initiation and subsequent abuse of drugs. Adolescents may be especially vulnerable to relapse, and a critical aspect of drug abuse is that it is a chronically relapsing disorder. However, little is known of how vulnerability factors such as adolescence are related to conditions that induce relapse, triggered by the drug itself, drug-associated cues, or stress. Objective The purpose of this study was to compare adolescent and adult rats on drug-, cue-, and stress-induced reinstatement of cocaine-seeking behavior. Methods On postnatal days 23 (adolescents) and 90 (adults), rats were implanted with intravenous catheters and trained to lever press for i.v. infusions of cocaine (0.4 mg/kg) during two daily 2-h sessions. The rats then self-administered i.v. cocaine for ten additional sessions. Subsequently, visual and auditory stimuli that signaled drug delivery were unplugged, and rats were allowed to extinguish lever pressing for 20 sessions. Rats were then tested on cocaine-, cue-, and yohimbine (stress)-induced cocaine seeking using a within-subject multicomponent reinstatement procedure. Results Results indicated that adolescents had heightened cocaine seeking during maintenance and extinction compared to adults. During reinstatement, adolescents (vs adults) responded more following cocaine- and yohimbine injections, while adults (vs adolescents) showed greater responding following presentations of drug-associated cues. Conclusion These results demonstrated that adolescents and adults differed across several measures of drug-seeking behavior, and adolescents may be especially vulnerable to relapse precipitated by drugs and stress. PMID:19953228

Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists

PubMed Central

Nelson, Andrew J. D.; Killcross, Simon

2013-01-01

Repeated exposure to the psychostimulant amphetamine has been shown to disrupt goal-directed instrumental actions and promote the early and abnormal development of goal-insensitive habitual responding (Nelson and Killcross, 2006). To investigate the neuropharmacological specificity of this effect as well as restore goal-directed responding in animals with pre-training amphetamine exposure, animals were treated with the non-selective dopamine antagonist α-flupenthixol, the selective D1 antagonist SCH 23390 or the selective D2 antagonist eticlopride, prior to instrumental training (three sessions). Subsequently, the reinforcer was paired with LiCL-induced gastric-malaise and animals were given a test of goal-sensitivity both in extinction and reacquisition. The effect of these dopaminergic antagonists on the sensitivity of lever press performance to outcome devaluation was assessed in animals with pre-training exposure to amphetamine (Experiments 1A–C) or in non-sensitized animals (Experiment 2). Both α-flupenthixol and SCH23390 reversed accelerated habit formation following amphetamine sensitization. However, eticlopride appeared to enhance this effect and render instrumental performance compulsive as these animals were unable to inhibit responding both in extinction and reacquisition, even though a consumption test confirmed they had acquired an aversion to the reinforcer. These findings demonstrate that amphetamine induced-disruption of goal-directed behavior is mediated by activity at distinct dopamine receptor subtypes and may represent a putative model of the neurochemical processes involved in the loss of voluntary control over behavior. PMID:23720609

Intravenous Alcohol Self-Administration in the P Rat

PubMed Central

Windisch, Kyle A.; Kosobud, Ann E. K.; Czachowski, Cristine L.

2014-01-01

Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally “relevant” effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding “non-pharmacological” effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol’s effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol self-administration methodology cannot overcome the aversive properties of ethanol via this route in the rat. PMID:24835637

Individualized tracking of self-directed motor learning in group-housed mice performing a skilled lever positioning task in the home cage.

PubMed

Silasi, Gergely; Boyd, Jamie D; Bolanos, Federico; LeDue, Jeff M; Scott, Stephen H; Murphy, Timothy H

2018-01-01

Skilled forelimb function in mice is traditionally studied through behavioral paradigms that require extensive training by investigators and are limited by the number of trials individual animals are able to perform within a supervised session. We developed a skilled lever positioning task that mice can perform within their home cage. The task requires mice to use their forelimb to precisely hold a lever mounted on a rotary encoder within a rewarded position to dispense a water reward. A Raspberry Pi microcomputer is used to record lever position during trials and to control task parameters, thus making this low-footprint apparatus ideal for use within animal housing facilities. Custom Python software automatically increments task difficulty by requiring a longer hold duration, or a more accurate hold position, to dispense a reward. The performance of individual animals within group-housed mice is tracked through radio-frequency identification implants, and data stored on the microcomputer may be accessed remotely through an active internet connection. Mice continuously engage in the task for over 2.5 mo and perform ~500 trials/24 h. Mice required ~15,000 trials to learn to hold the lever within a 10° range for 1.5 s and were able to further refine movement accuracy by limiting their error to a 5° range within each trial. These results demonstrate the feasibility of autonomously training group-housed mice on a forelimb motor task. This paradigm may be used in the future to assess functional recovery after injury or cortical reorganization induced by self-directed motor learning. NEW & NOTEWORTHY We developed a low-cost system for fully autonomous training of group-housed mice on a forelimb motor task. We demonstrate the feasibility of tracking both end-point, as well as kinematic performance of individual mice, with each performing thousands of trials over 2.5 mo. The task is run and controlled by a Raspberry Pi microcomputer, which allows for cages to be monitored remotely through an active internet connection.

Individual Differences in the Attribution of Incentive Salience to a Pavlovian Alcohol Cue

PubMed Central

Villaruel, Franz R.; Chaudhri, Nadia

2016-01-01

Individual differences exist in the attribution of incentive salience to conditioned stimuli associated with food. Here, we investigated whether individual differences also manifested with a Pavlovian alcohol conditioned stimulus (CS). We compiled data from five experiments that used a Pavlovian autoshaping paradigm and tests of conditioned reinforcement. In all experiments, male, Long-Evans rats with unrestricted access to food and water were acclimated to 15% ethanol. Next, rats received Pavlovian autoshaping training, in which a 10 s presentation of a retractable lever served as the CS and 0.2 mL of 15% ethanol served as the unconditioned stimulus (US). Finally, rats underwent conditioned reinforcement tests in which nose-pokes to an active aperture led to brief presentations of the lever-CS, but nose-pokes to an inactive aperture had no consequence. Rats were categorized as sign-trackers, goal-trackers and intermediates based on a response bias score that reflected their tendencies to sign-track or goal-track at different times during training. We found that distinct groups of rats either consistently interacted with the lever-CS (“sign-trackers”) or routinely approached the port during the lever-CS (“goal-trackers”) across a majority of the training sessions. However, some individuals (“shifted sign-trackers”) with an early tendency to goal-track later shifted to comparable asymptotic levels of sign-tracking as the group identified as sign-trackers. The lever-CS functioned as a conditioned reinforcer for sign-trackers and shifted sign-trackers, but not for goal-trackers. These results provide evidence of robust individual differences in the extent to which a Pavlovian alcohol cue gains incentive salience and functions as a conditioned reinforcer. PMID:28082877

Individual Differences in the Attribution of Incentive Salience to a Pavlovian Alcohol Cue.

PubMed

Villaruel, Franz R; Chaudhri, Nadia

2016-01-01

Individual differences exist in the attribution of incentive salience to conditioned stimuli associated with food. Here, we investigated whether individual differences also manifested with a Pavlovian alcohol conditioned stimulus (CS). We compiled data from five experiments that used a Pavlovian autoshaping paradigm and tests of conditioned reinforcement. In all experiments, male, Long-Evans rats with unrestricted access to food and water were acclimated to 15% ethanol. Next, rats received Pavlovian autoshaping training, in which a 10 s presentation of a retractable lever served as the CS and 0.2 mL of 15% ethanol served as the unconditioned stimulus (US). Finally, rats underwent conditioned reinforcement tests in which nose-pokes to an active aperture led to brief presentations of the lever-CS, but nose-pokes to an inactive aperture had no consequence. Rats were categorized as sign-trackers, goal-trackers and intermediates based on a response bias score that reflected their tendencies to sign-track or goal-track at different times during training. We found that distinct groups of rats either consistently interacted with the lever-CS ("sign-trackers") or routinely approached the port during the lever-CS ("goal-trackers") across a majority of the training sessions. However, some individuals ("shifted sign-trackers") with an early tendency to goal-track later shifted to comparable asymptotic levels of sign-tracking as the group identified as sign-trackers. The lever-CS functioned as a conditioned reinforcer for sign-trackers and shifted sign-trackers, but not for goal-trackers. These results provide evidence of robust individual differences in the extent to which a Pavlovian alcohol cue gains incentive salience and functions as a conditioned reinforcer.

Effects of lesions of the amygdala central nucleus on autoshaped lever pressing

PubMed Central

Chang, Stephen E.; Wheeler, Daniel S.; Holland, Peter C.

2012-01-01

Neutral cues paired with rewards often appear to acquire motivational significance, as if the incentive motivational value of the reward is transferred to the cue. Such cues have been reported to modulate the performance of instrumental action (Pavlovian-instrumental transfer, PIT), serve as conditioned reinforcers in the establishment of new learning, and be the targets of approach and other cue-directed behaviors. Here we examined the effects of lesions of the amygdala central nucleus (CeA) on the acquisition of discriminative autoshaped lever-pressing. Insertion of one lever into the experimental chamber was reinforced by sucrose delivery, but insertion of another lever was not reinforced. Although sucrose delivery was not contingent on lever pressing, both CeA- and sham-lesioned rats rapidly came to press the reinforced but not the nonreinforced lever. Despite their showing little evidence of impairments in autoshaped lever pressing, these same CeA-lesioned rats showed significant deficits in the expression of PIT in a subsequent phase of the experiment. The lack of impaired autoshaping in CeA-lesioned rats contrasts with effects previously reported for conditioned orienting responses (ORs) and for other putative measures of incentive learning including PIT and conditioned approach to visual cues. PMID:22386516

Opposite Effects of Basolateral Amygdala Inactivation on Context-Induced Relapse to Cocaine Seeking after Extinction versus Punishment.

PubMed

Pelloux, Yann; Minier-Toribio, Angelica; Hoots, Jennifer K; Bossert, Jennifer M; Shaham, Yavin

2018-01-03

Studies using the renewal procedure showed that basolateral amygdala (BLA) inactivation inhibits context-induced relapse to cocaine-seeking after extinction. Here, we determined whether BLA inactivation would also inhibit context-induced relapse after drug-reinforced responding is suppressed by punishment, an animal model of human relapse after self-imposed abstinence due to adverse consequences of drug use. We also determined the effect of central amygdala (CeA) inactivation on context-induced relapse.We trained rats to self-administer cocaine for 12 d (6 h/d) in Context A and then exposed them to either extinction or punishment training for 8 d in Context B. During punishment, 50% of cocaine-reinforced lever-presses produced an aversive footshock of increasing intensity (0.1-0.5 or 0.7 mA). We then tested the rats for relapse to cocaine seeking in the absence of cocaine or shock in Contexts A and B after BLA or CeA injections of vehicle or GABA agonists (muscimol-baclofen). We then retrained the rats for cocaine self-administration in Context A, repunished or re-extinguished lever pressing in Context B, and retested for relapse after BLA or CeA inactivation.BLA or CeA inactivation decreased context-induced relapse in Context A after extinction in Context B. BLA, but not CeA, inactivation increased context-induced relapse in Context A after punishment in Context B. BLA or CeA inactivation provoked relapse in Context B after punishment but not extinction. Results demonstrate that amygdala's role in relapse depends on the method used to achieve abstinence and highlights the importance of studying relapse under abstinence conditions that more closely mimic the human condition. SIGNIFICANCE STATEMENT Relapse to drug use during abstinence is often provoked by re-exposure to the drug self-administration environment or context. Studies using the established extinction-reinstatement rodent model of drug relapse have shown that inactivation of the basolateral amygdala inhibits context-induced drug relapse after extinction of the drug-reinforced responding. Here, we determined whether basolateral amygdala inactivation would also inhibit relapse after drug-reinforced responding is suppressed by punishment, a model of human relapse after self-imposed abstinence. Unexpectedly, we found that basolateral amygdala inactivation had opposite effects on relapse provoked by re-exposure to the drug self-administration environment after extinction versus punishment. Our results demonstrate that depending on the historical conditions that lead to abstinence, amygdala activity can either promote or inhibit relapse. Copyright © 2018 the authors 0270-6474/18/380051-09$15.00/0.

Apparatus for Teaching Physics.

ERIC Educational Resources Information Center

Minnix, Richard B., Ed.; Carpenter, D. Rae, Jr., Ed.

1983-01-01

Describes four body-lever models (biceps, triceps, back lever when lifting, foot lever and Achilles tendon muscle) used in noncalculus physics courses. Instructions for constructing the wooden models are provided. Also describes an improvement on a centripetal-force apparatus so that it is easier to operate. (JN)

Switch Using Radio Frequency Identification

NASA Technical Reports Server (NTRS)

Fink, Patrick W. (Inventor); Kennedy, Timothy F. (Inventor); Lin, Gregory Y. (Inventor); Ngo, Phong H. (Inventor)

2015-01-01

Disclosed is an apparatus for use as a switch. In one embodiment, the switch comprises at least one RFID tag, each RFID tag comprising an antenna element and an RFID integrated circuit, at least one source element, and at least one lever arm. Each lever arm is connected to one of the RFID tags, and each lever arm is capable of two positions. One of the positions places the lever arm and the RFID tag connected thereto into alignment with the source element. Other embodiments are also described.

Interaction between the basolateral amygdala and dorsal hippocampus is critical for cocaine memory reconsolidation and subsequent drug context-induced cocaine-seeking behavior in rats

PubMed Central

Wells, Audrey M.; Lasseter, Heather C.; Xie, Xiaohu; Cowhey, Kate E.; Reittinger, Andrew M.; Fuchs, Rita A.

2011-01-01

Contextual stimulus control over instrumental drug-seeking behavior relies on the reconsolidation of context-response-drug associative memories into long-term memory storage following retrieval-induced destabilization. According to previous studies, the basolateral amygdala (BLA) and dorsal hippocampus (DH) regulate cocaine-related memory reconsolidation; however, it is not known whether these brain regions interact or independently control this phenomenon. To investigate this question, rats were trained to lever press for cocaine reinforcement in a distinct environmental context followed by extinction training in a different context. Rats were then briefly re-exposed to the cocaine-paired context to destabilize cocaine-related memories, or they were exposed to an unpaired context. Immediately thereafter, the rats received unilateral microinfusions of anisomycin (ANI) into the BLA plus baclofen/muscimol (B/M) into the contralateral (BLA/DH disconnection) or ipsilateral DH, or they received contralateral or ipsilateral microinfusions of vehicle. They then remained in their home cages overnight or for 21 d, followed by additional extinction training and a test of cocaine-seeking behavior (nonreinforced active lever responding). BLA/DH disconnection following re-exposure to the cocaine-paired context, but not the unpaired context, impaired subsequent drug context-induced cocaine-seeking behavior relative to vehicle or ipsilateral ANI + B/M treatment. Prolonged home cage stay elicited a time-dependent increase, or incubation, of drug-context-induced cocaine-seeking behavior, and BLA/DH disconnection inhibited this incubation effect despite some recovery of cocaine-seeking behavior. Thus, the BLA and DH interact to regulate the reconsolidation of cocaine-related associative memories, thereby facilitating the ability of drug-paired contexts to trigger cocaine-seeking behavior and contributing to the incubation of cocaine-seeking behavior. PMID:22005750

Involvement of the Lateral Orbitofrontal Cortex in Drug Context-induced Reinstatement of Cocaine-seeking Behavior in Rats

PubMed Central

Lasseter, Heather C.; Ramirez, Donna R.; Xie, Xiaohu; Fuchs, Rita A.

2009-01-01

Orbitofrontal cortex (OFC) damage produces impaired decision-making, impulsivity, and perseveration and potentially contributes to compulsive drug seeking in cocaine users. To further explore this phenomenon, we assessed the role of the lateral OFC (lOFC) in drug context-induced cocaine-seeking behavior in the reinstatement model of drug relapse. Rats were trained to lever press for intravenous cocaine infusions in a distinct environmental context (cocaine-paired context) followed by extinction training in a different context (extinction-paired context). Reinstatement of cocaine seeking (non-reinforced lever presses) was assessed in the cocaine context in the absence of response-contingent stimuli. In experiment 1, we evaluated whether acute inhibition of lOFC output alters context-induced cocaine-seeking behavior by infusing the GABAB+A agonists, baclofen+muscimol, or vehicle into the lOFC immediately before exposure to the cocaine-paired context. In experiments 2–3, we assessed how prolonged loss of lOFC output affects drug context-induced cocaine seeking by administering bilateral NMDA or sham lesions of the lOFC either before or after self-administration and extinction training. Remarkably, OFC functional inactivation attenuated, post-training lesions failed to alter, and pre-training lesions potentiated drug context-induced cocaine seeking without altering responding in the extinction context. These results suggest that neural activity in the lOFC promotes context-induced cocaine-seeking behavior. However, prolonged loss of lOFC output enhances the motivational salience of cocaine-paired contextual stimuli likely by eliciting compensatory neuroadaptations, with the effects of post-training lOFC lesions reflecting an intermediate state of compensatory neuroplasticity. Overall, these findings support the idea that OFC dysfunction may promote cue reactivity and enhance relapse propensity in cocaine users. PMID:19769591

Silexan, an essential oil from flowers of Lavandula angustifolia, is not recognized as benzodiazepine-like in rats trained to discriminate a diazepam cue.

PubMed

Silenieks, Leo B; Koch, Egon; Higgins, Guy A

2013-01-15

Recently, an essential oil of selected quality produced from the flowering tops of Lavandula angustifolia Mill. by steam distillation (Silexan) has been approved in Germany for the treatment of restlessness in case of anxious mood. Based on the observed clinical effects, it has been speculated that lavender oil may exert benzodiazepine-like action including the known dependence and abuse potential of this class of drugs. Although no evidence for such an activity was generated during the long-standing medicinal use of lavender oil, further preclinical investigations were now conducted to evaluate this potential side effect in more detail. Twelve adult, male, Sprague-Dawley rats were trained to discriminate the benzodiazepine drug diazepam (2 mg/kg i.p.) from saline using a two-lever operant procedure. After approximately 40 training sessions the majority of rats learned the discrimination and pre-treatment with ascending doses of diazepam (0.3-2 mg/kg i.p.) produced a dose related generalization to the diazepam cue. In these same animals Silexan was administered to see if animals recognized the drug as "diazepam-like" i.e. generalized to diazepam or "saline-like". Silexan tested at doses 3-30 mg/kg i.p. produced almost exclusively (>90%) saline-like responding. Also there was no effect of Silexan on response rate, i.e. rate of lever pressing, at any dose suggesting that the test article is well tolerated and does not exert a sedating effect. In sum, Silexan has no diazepam-like interoceptive property in adult, male rats. This suggests that Silexan does not share the potential of benzodiazepines to induce the development of tolerance, dependence and addiction. Copyright © 2012 Elsevier GmbH. All rights reserved.

Role of projections from ventral subiculum to nucleus accumbens shell in context-induced reinstatement of heroin seeking in rats.

PubMed

Bossert, Jennifer M; Adhikary, Sweta; St Laurent, Robyn; Marchant, Nathan J; Wang, Hui-Ling; Morales, Marisela; Shaham, Yavin

2016-05-01

In humans, exposure to contexts previously associated with heroin use can provoke relapse. In rats, exposure to heroin-paired contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. We previously demonstrated that the projections from ventral medial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) shell play a role in this reinstatement. The ventral subiculum (vSub) sends glutamate projections to NAc shell and vmPFC. Here, we determined whether these projections contribute to context-induced reinstatement. We trained rats to self-administer heroin (0.05-0.1 mg/kg/infusion) for 3 h per day for 12 days; drug infusions were paired with a discrete tone-light cue. Lever pressing in the presence of the discrete cue was subsequently extinguished in a different context. We then tested the rats for reinstatement in the heroin- and extinction-associated contexts under extinction conditions. We combined Fos with the retrograde tracer Fluoro-Gold (FG) to determine projection-specific activation during the context-induced reinstatement tests. We also used anatomical disconnection procedures to determine whether the vSub → NAc shell and vSub → vmPFC projections are functionally involved in this reinstatement. Exposure to the heroin but not the extinction context reinstated lever pressing. Context-induced reinstatement of heroin seeking was associated with increased Fos expression in vSub neurons, including those projecting to NAc shell and vmPFC. Anatomical disconnection of the vSub → NAc shell projection, but not the vSub → vmPFC projection, decreased this reinstatement. Our data indicate that the vSub → NAc shell glutamatergic projection, but not the vSub → vmPFC projection, contributes to context-induced reinstatement of heroin seeking.

The speed of cocaine delivery determines the subsequent motivation to self-administer the drug.

PubMed

Minogianis, Ellie-Anna; Lévesque, Daniel; Samaha, Anne-Noël

2013-12-01

The rapid delivery of drugs of abuse to the brain is associated with an increased likelihood and severity of addiction. Here we evaluated the hypothesis that rapidly delivered cocaine facilitates the addiction process by promoting the development of enhanced motivation for the drug. Rats lever-pressed for cocaine delivered intravenously over 5 or 90 s under fixed ratio (FR) during 6-h sessions. The motivation for cocaine was subsequently assessed using a progressive ratio (PR) schedule, where each successive drug injection cost an exponentially greater number of lever presses, until the cessation of responding. Throughout all self-administration sessions, all rats could only take one injection every 90 s. The 5-s groups self-administered more drug than the 90-s groups across the FR sessions. Under PR, animals that had chronically self-administered rapidly delivered cocaine took more cocaine across a range of doses and regardless of whether the drug was delivered over 5 or 90 s during PR testing. The speed of delivery also determined the long-term neurobiological impact of cocaine. Fourteen days following cocaine withdrawal, caudate-putamen D2 levels were decreased only in the 90-s rats, and quinpirole-mediated Gα(i/o)-protein activation was increased to a greater extent in the 90- vs 5-s rats. Thus, rapid delivery promotes the pursuit of cocaine in the face of rising costs and alters cocaine-induced changes in striatal D2 receptor number and function. As such, rapidly delivered cocaine might facilitate addiction because it more readily alters brain motivation circuits in ways that contribute to the compulsive pursuit of the drug.

Biology-Inspired Explorers for Space Systems

NASA Astrophysics Data System (ADS)

Ramohalli, Kumar; Lozano, Peter; Furfaro, Roberto

2002-01-01

Building upon three innovative technologies, each of which received a NTR award from NASA, a specific explorer is described. This "robot" does away with conventional gears, levers, pulleys,.... And uses "Muscle Materials" instead; these shape-memory materials, formerly in the Nickel-Titanium family, but now in the much wider class of ElectroActivePolymers(EAP), have the ability to precisely respond to pre"programmed" shape changes upon application of an electrical input. Of course, the pre"programs" are at the molecular level, much like in biological systems. Another important feature is the distributed power. That is, the power use in the "limbs" is distributed, so that if one "limb" should fail, the others can still function. The robot has been built and demonstrated to the media (newspapers and television). The fundamental control aspects are currently being worked upon, and we expect to have a more complete mathematical description of its operation. Future plans, and specific applications for reliable planetary exploration will be outlined.

Remote control of molecular motors using light-activated gearshifting

NASA Astrophysics Data System (ADS)

Bryant, Zev

2013-03-01

Engineering molecular motors with dynamically controllable properties will allow selective perturbation of mechanical processes in vivo and provide sophisticated components for directed nanoscale transport in vitro. We previously constructed myosin motors that respond to a change in [Ca++] by reversing their direction of motion along the polarized actin filament. To expand the potential applications of controllable molecular motors, we have now developed myosins that shift gears in response to blue light illumination. Light is a versatile control signal that can be readily modulated in time and space, and is generally orthogonal to cellular signaling. Using structure-guided protein engineering, we have incorporated LOV photoreceptor domains into the lever arms of chimeric myosins, resulting in motors that robustly speed up, slow down, or switch directions upon illumination. These genetically encoded motors should be directly deployable inside living cells. Our successful designs include constructs based on two different myosin classes, and we show that optical velocity control can be implemented in motors that move at microns/sec speeds, enabling practical biological and bioengineering applications.

Using Indices of Fidelity to Intervention Core Components to Identify Program Active Ingredients

ERIC Educational Resources Information Center

Abry, Tashia; Hulleman, Chris S.; Rimm-Kaufman, Sara E.

2015-01-01

Identifying the active ingredients of an intervention--intervention-specific components serving as key levers of change--is crucial for unpacking the intervention black box. Measures of intervention fidelity can be used to identify specific active ingredients, yet such applications are rare. We illustrate how fidelity measures can be used to…

49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...

49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...

49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...

49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...

Inhibition of protein synthesis but not β-adrenergic receptors blocks reconsolidation of a cocaine-associated cue memory

PubMed Central

Dunbar, Amber B.

2016-01-01

Previously consolidated memories have the potential to enter a state of lability upon memory recall, during which time the memory can be altered before undergoing an additional consolidation-like process and being stored again as a long-term memory. Blocking reconsolidation of aberrant memories has been proposed as a potential treatment for psychiatric disorders including addiction. Here we investigated of the effect of systemically administering the protein synthesis inhibitor cycloheximide or the β-adrenergic antagonist propranolol on reconsolidation. Rats were trained to self-administer cocaine, during which each lever press resulted in the presentation of a cue paired with an intravenous infusion of cocaine. After undergoing lever press extinction to reduce operant responding, the cue memory was reactivated and rats were administered systemic injections of propranolol, cycloheximide, or vehicle. Post-reactivation cycloheximide, but not propranolol, resulted in a reactivation-dependent decrease in cue-induced reinstatement, indicative of reconsolidation blockade by protein synthesis inhibition. The present data indicate that systemically targeting protein synthesis as opposed to the β-adrenergic system may more effectively attenuate the reconsolidation of a drug-related memory and decrease drug-seeking behavior. PMID:27421890

Inhibition of protein synthesis but not β-adrenergic receptors blocks reconsolidation of a cocaine-associated cue memory.

PubMed

Dunbar, Amber B; Taylor, Jane R

2016-08-01

Previously consolidated memories have the potential to enter a state of lability upon memory recall, during which time the memory can be altered before undergoing an additional consolidation-like process and being stored again as a long-term memory. Blocking reconsolidation of aberrant memories has been proposed as a potential treatment for psychiatric disorders including addiction. Here we investigated of the effect of systemically administering the protein synthesis inhibitor cycloheximide or the β-adrenergic antagonist propranolol on reconsolidation. Rats were trained to self-administer cocaine, during which each lever press resulted in the presentation of a cue paired with an intravenous infusion of cocaine. After undergoing lever press extinction to reduce operant responding, the cue memory was reactivated and rats were administered systemic injections of propranolol, cycloheximide, or vehicle. Post-reactivation cycloheximide, but not propranolol, resulted in a reactivation-dependent decrease in cue-induced reinstatement, indicative of reconsolidation blockade by protein synthesis inhibition. The present data indicate that systemically targeting protein synthesis as opposed to the β-adrenergic system may more effectively attenuate the reconsolidation of a drug-related memory and decrease drug-seeking behavior. © 2016 Dunbar and Taylor; Published by Cold Spring Harbor Laboratory Press.

Evidence for positive, but not negative, behavioral contrast with wheel-running reinforcement on multiple variable-ratio schedules.

PubMed

Belke, Terry W; Pierce, W David

2016-12-01

Rats responded on a multiple variable-ratio (VR) 10 VR 10 schedule of reinforcement in which lever pressing was reinforced by the opportunity to run in a wheel for 30s in both the changed (manipulated) and unchanged components. To generate positive contrast, the schedule of reinforcement in the changed component was shifted to extinction; to generate negative contrast, the schedule was shifted to VR 3. With the shift to extinction in the changed component, wheel-running and local lever-pressing rates increased in the unchanged component, a result supporting positive contrast; however, the shift to a VR 3 schedule in the changed component showed no evidence of negative contrast in the unaltered setting, only wheel running decreased in the unchanged component. Changes in wheel-running rates across components were consistent in showing a compensation effect, depending on whether the schedule manipulation increased or decreased opportunities for wheel running in the changed component. These findings are the first to demonstrate positive behavioral contrast on a multiple schedule with wheel running as reinforcement in both components. Copyright © 2016 Elsevier B.V. All rights reserved.

Yohimbine reinstates extinguished 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) seeking in rats with prior exposure to chronic yohimbine.

PubMed

Ball, Kevin T; Jarsocrak, Hanna; Hyacinthe, Johanna; Lambert, Justina; Lockowitz, James; Schrock, Jordan

2015-11-01

Although exposure to acute stress has been shown to reinstate extinguished responding for a wide variety of drugs, no studies have investigated stress-induced reinstatement in animals with a history of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) self-administration. Thus, rats were trained to press a lever for MDMA (0.50 mg/kg/infusion) in daily sessions, and lever pressing was subsequently extinguished in the absence of MDMA and conditioned cues (light and tone). We then tested the ability of acute yohimbine (2.0 mg/kg), a pharmacological stressor, to reinstate lever-pressing under extinction conditions. Additionally, to model chronic stress, some rats were injected daily with yohimbine (5.0 mg/kg × 10 days) prior to reinstatement tests. To assess dopaminergic involvement, chronic yohimbine injections were combined with injections of SCH-23390 (0.0 or 10.0 μg/kg), a dopamine D1-like receptor antagonist. In a separate experiment, rats with a history of food self-administration were treated and tested in the same way. Results showed that acute yohimbine injections reinstated extinguished MDMA and food seeking, but only in rats with a history of chronic yohimbine exposure. Co-administration of SCH-23390 with chronic yohimbine injections prevented the potentiation of subsequent food seeking, but not MDMA seeking. These results suggest that abstinent MDMA users who also are exposed to chronic stress may be at increased risk for future relapse, and also that the effects of chronic stress on relapse may be mediated by different mechanisms depending on one's drug use history. Copyright © 2015 Elsevier B.V. All rights reserved.

Confirmation of linear system theory prediction: Changes in Herrnstein's k as a function of changes in reinforcer magnitude.

PubMed

McDowell, J J; Wood, H M

1984-03-01

Eight human subjects pressed a lever on a range of variable-interval schedules for 0.25 cent to 35.0 cent per reinforcement. Herrnstein's hyperbola described seven of the eight subjects' response-rate data well. For all subjects, the y-asymptote of the hyperbola increased with increasing reinforcer magnitude and its reciprocal was a linear function of the reciprocal of reinforcer magnitude. These results confirm predictions made by linear system theory; they contradict formal properties of Herrnstein's account and of six other mathematical accounts of single-alternative responding.

Confirmation of linear system theory prediction: Changes in Herrnstein's k as a function of changes in reinforcer magnitude

PubMed Central

McDowell, J. J; Wood, Helena M.

1984-01-01

Eight human subjects pressed a lever on a range of variable-interval schedules for 0.25¢ to 35.0¢ per reinforcement. Herrnstein's hyperbola described seven of the eight subjects' response-rate data well. For all subjects, the y-asymptote of the hyperbola increased with increasing reinforcer magnitude and its reciprocal was a linear function of the reciprocal of reinforcer magnitude. These results confirm predictions made by linear system theory; they contradict formal properties of Herrnstein's account and of six other mathematical accounts of single-alternative responding. PMID:16812366

Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigm.

PubMed

Day, Jeremy J; Wheeler, Robert A; Roitman, Mitchell F; Carelli, Regina M

2006-03-01

Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism's ability to track and secure natural rewards, but may also contribute to the compulsive nature of drug addiction. Here, we examined the activity of individual nucleus accumbens (NAc) neurons during an autoshaping paradigm. One conditioned stimulus (CS+, a retractable lever presented for 10 s) was immediately followed by the delivery of a 45-mg sucrose pellet to a food receptacle, while another stimulus (CS-, a separate retractable lever presented for 10 s) was never followed by sucrose. Approach responses directed at the CS+ and CS- were recorded as lever presses and had no experimental consequence. Rats (n = 9) selectively approached the CS+ on more than 80% of trials and were surgically prepared for electrophysiological recording. Of 76 NAc neurons, 57 cells (75%) exhibited increases and/or decreases in firing rate (i.e. termed 'phasically active') during the CS+ presentation and corresponding approach response. Forty-seven percent of phasically active cells (27 out of 57) were characterized by time-locked but transient increases in cell firing, while 53% (30 out of 57) showed a significant reduction in firing for the duration of the CS+. In contrast, the same excitatory subpopulation exhibited smaller increases in activity relative to CS- onset, while the inhibitory subpopulation showed no change in firing during the CS- period. The magnitude and prevalence of cue-related neural responses reported here indicates that the NAc encodes biologically significant, repetitive approach responses that may model the compulsive nature of drug addiction in humans.

The attribution of incentive salience to Pavlovian alcohol cues: a shift from goal-tracking to sign-tracking.

PubMed

Srey, Chandra S; Maddux, Jean-Marie N; Chaudhri, Nadia

2015-01-01

Environmental stimuli that are reliably paired with alcohol may acquire incentive salience, a property that can operate in the use and abuse of alcohol. Here we investigated the incentive salience of Pavlovian alcohol cues using a preclinical animal model. Male, Long-Evans rats (Harlan) with unrestricted access to food and water were acclimated to drinking 15% ethanol (v/v) in their home-cages. Rats then received Pavlovian autoshaping training in which the 10 s presentation of a retractable lever served as the conditioned stimulus (CS) and 15% ethanol served as the unconditioned stimulus (US) (0.2 ml/CS; 12 CS presentations/session; 27 sessions). Next, in an operant test of conditioned reinforcement, nose pokes into an active aperture delivered presentations of the lever-CS, whereas nose pokes into an inactive aperture had no consequences. Across initial autoshaping sessions, goal-tracking behavior, as measured by entries into the fluid port where ethanol was delivered, developed rapidly. However, with extended training goal-tracking diminished, and sign-tracking responses, as measured by lever-CS activations, emerged. Control rats that received explicitly unpaired CS and US presentations did not show goal-tracking or sign-tracking responses. In the test for conditioned reinforcement, rats with CS-US pairings during autoshaping training made more active relative to inactive nose pokes, whereas rats in the unpaired control group did not. Moreover, active nose pokes were positively correlated with sign-tracking behavior during autoshaping. Extended training may produce a shift in the learned properties of Pavlovian alcohol cues, such that after initially predicting alcohol availability they acquire robust incentive salience.

Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors.

PubMed

Smith, R L; Canton, H; Barrett, R J; Sanders-Bush, E

1998-11-01

Extensive behavioral and biochemical evidence suggests an agonist role at the 5-HT2A receptor, and perhaps the 5-HT2C receptor, in the mechanism of action of hallucinogenic drugs. However the published in vitro pharmacological properties of N,N-dimethyltryptamine (DMT), an hallucinogenic tryptamine analog, are not consistent with this hypothesis. We, therefore, undertook an extensive investigation into the properties of DMT at 5-HT2A and 5-HT2C receptors. In fibroblasts transfected with the 5-HT2A receptor or the 5-HT2C receptor, DMT activated the major intracellular signaling pathway (phosphoinositide hydrolysis) to an extent comparable to that produced by serotonin. Because drug efficacy changes with receptor density and cellular microenvironment, we also examined the properties of DMT in native preparations using a behavioral and biochemical approach. Rats were trained to discriminate an antagonist ketanserin from an agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in a two-lever choice paradigm. Pharmacological studies showed that responding on the DOI and ketanserin lever reflected agonist and antagonist activity at 5-HT2A receptors, and hence, was a suitable model for evaluating the in vivo functional properties of DMT. Like other 5-HT2A receptor agonists, DMT substituted fully for DOI. Intact choroid plexus was used to evaluate the agonist properties at endogenous 5-HT2C receptors; DMT was a partial agonist at 5-HT2C receptors in this native preparation. Thus, we conclude that DMT behaves as an agonist at both 5-HT2A and 5-HT2A receptors. One difference was evident in that the 5-HT2C, but not the 5-HT2A, receptor showed a profound desensitization to DMT over time. This difference is interesting in light of the recent report that the hallucinogenic activity of DMT does not tolerate in humans and suggests the 5-HT2C receptor plays a less prominent role in the action of DMT.

40 CFR 1065.310 - Torque calibration.

Code of Federal Regulations, 2014 CFR

2014-07-01

... force is measured. The lever arm must be perpendicular to gravity (i.e., horizontal), and it must be... known distance along a lever arm. Make sure the weights' lever arm is perpendicular to gravity (i.e... Earth's gravity, as described in § 1065.630. Calculate the reference torque as the weights' reference...

Contingency Tracking during Unsignaled Delayed Reinforcement

ERIC Educational Resources Information Center

Keely, Josue; Feola, Tyler; Lattal, Kennon A.

2007-01-01

Three experiments were conducted with rats in which responses on one lever (labeled the functional lever) produced reinforcers after an unsignaled delay period that reset with each response during the delay. Responses on a second, nonfunctional, lever did not initiate delays, but, in the first and third experiments, such responses during the last…

40 CFR 1065.310 - Torque calibration.

Code of Federal Regulations, 2013 CFR

2013-07-01

... reference force is measured. The lever arm must be perpendicular to gravity (i.e., horizontal), and it must... known distance along a lever arm. Make sure the weights' lever arm is perpendicular to gravity (i.e... gravity (using this equation: force = mass · acceleration). The local acceleration of gravity, a g, at...

40 CFR 1065.310 - Torque calibration.

Code of Federal Regulations, 2012 CFR

2012-07-01

... reference force is measured. The lever arm must be perpendicular to gravity (i.e., horizontal), and it must... known distance along a lever arm. Make sure the weights' lever arm is perpendicular to gravity (i.e... gravity (using this equation: force = mass · acceleration). The local acceleration of gravity, a g, at...

Modified compensation algorithm of lever-arm effect and flexural deformation for polar shipborne transfer alignment based on improved adaptive Kalman filter

NASA Astrophysics Data System (ADS)

Wang, Tongda; Cheng, Jianhua; Guan, Dongxue; Kang, Yingyao; Zhang, Wei

2017-09-01

Due to the lever-arm effect and flexural deformation in the practical application of transfer alignment (TA), the TA performance is decreased. The existing polar TA algorithm only compensates a fixed lever-arm without considering the dynamic lever-arm caused by flexural deformation; traditional non-polar TA algorithms also have some limitations. Thus, the performance of existing compensation algorithms is unsatisfactory. In this paper, a modified compensation algorithm of the lever-arm effect and flexural deformation is proposed to promote the accuracy and speed of the polar TA. On the basis of a dynamic lever-arm model and a noise compensation method for flexural deformation, polar TA equations are derived in grid frames. Based on the velocity-plus-attitude matching method, the filter models of polar TA are designed. An adaptive Kalman filter (AKF) is improved to promote the robustness and accuracy of the system, and then applied to the estimation of the misalignment angles. Simulation and experiment results have demonstrated that the modified compensation algorithm based on the improved AKF for polar TA can effectively compensate the lever-arm effect and flexural deformation, and then improve the accuracy and speed of TA in the polar region.

Analysis of Porosity Defects in Aluminum as Part Handle Motor Vehicle Lever Processed by High-pressure Die Casting

NASA Astrophysics Data System (ADS)

Anggraini, L.; Sugeng

2018-05-01

This research discusses the testing and analysis of cracking Aluminum (Al) material. Al as a handle lever was used for a braking device on a motor vehicle. Cracking of handle lever due to the part content of porosity from hydrogen gas. The existence of the H2 can be caused by the casting process and dies design that is less perfect, especially at the gate or brisket and overflow. This research is to optimize the process of making Al part handle lever, and the construction dies by following the standard. The results of these improvements were reevaluated through the chemical and mechanical testing properties stages, such as density test and tensile test on the workpiece as part handle lever. The loads on the tensile test are 25 kg and 35 kg, and the tensile test result has met the standard set by the motor vehicle company. The optimization result has the porosity defect can be reduced by 99 %. Therefore the best part handle lever can be produced.

The role of nicotinic receptor alpha 7 subunits in nicotine discrimination.

PubMed

Stolerman, I P; Chamberlain, S; Bizarro, L; Fernandes, C; Schalkwyk, L

2004-03-01

The subtypes of nicotinic receptors at which the behavioural effects of nicotine originate are not fully understood. The experiments described here use mice lacking the alpha7 subunit of nicotinic receptors to investigate the role of alpha7-containing receptors in nicotine discrimination. Wild-type and alpha7-knockout mice were trained in a two-lever nicotine discrimination procedure using a tandem schedule of food reinforcement. Mutant mice exhibited baseline rates of lever-pressing as low as 52.2% of rates in wild-type controls (n=21-24). Mutant and wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) at a similar rate (n=10-12) and reached similar final levels of accuracy (71.9 +/- 4.4% and 90.8 +/- 3.1% after 60 training sessions for 0.4 and 0.8 mg/kg training doses, respectively, in mutant mice, as compared with 75.0 +/- 6.5% and 87.6 +/- 4.8% for wild types). The genotypes exhibited similar steep dose-response curves for nicotine discrimination. In both genotypes, dose-response curves for mice trained with 0.8 mg/kg of nicotine were displaced three- to four-fold to the right as compared with those for the mice trained with the smaller dose. The predominant effect of nicotine on the overall rate of responding was a reduction at the largest doses tested and there was no difference between the genotypes. The results suggest that nicotinic receptors containing the alpha7 subunit do not contribute to the discriminative stimulus or response-rate-depressant effects of nicotine, although they may regulate baseline rates of operant responding.

Premature responding is associated with approach to a food cue in male and female heterogeneous stock rats

PubMed Central

King, Christopher P.; Palmer, Abraham A.; Solberg Woods, Leah C.; Hawk, Larry W.; Richards, Jerry B.; Meyer, Paul J.

2016-01-01

Rationale Disorders of behavioral regulation, including attention deficit hyperactivity disorder (ADHD) and drug addiction, are in part due to poor inhibitory control, attentional deficits, and hyper-responsivity to reward-associated cues. Objectives To determine whether these traits are related, we tested genetically variable male and female heterogeneous stock rats in the choice reaction time (CRT) task and Pavlovian conditioned approach (PavCA). Sex differences in the response to methylphenidate during the CRT were also assessed. Methods In the CRT task, rats were required to withhold responding until one of two lights indicated whether responses into a left or right port would be reinforced with water. Reaction time on correct trials and premature responses were the operational definitions of attention and response inhibition, respectively. Rats were also pre-treated with oral methylphenidate (0, 2, 4 mg/kg) during the CRT task to determine whether this drug would improve performance. Subsequently, during PavCA, presentation of an illuminated lever predicted the delivery of a food pellet into a food-cup. Lever-directed approach (sign-tracking) and food-cup approach (goal-tracking) were the primary measures, and rats were categorized as “sign-trackers” and “goal-trackers” using an index based on these measures. Results Sign-trackers made more premature responses than goal-trackers, but showed no differences in reaction time. There were sex differences in both tasks, with females having higher sign-tracking, completing more CRT trials, and making more premature responses after methylphenidate administration. Conclusions These results indicate that response inhibition is related to reward-cue responsivity, suggesting that these traits are influenced by common genetic factors. PMID:27146401

Effects of environmental enrichment on self-administration of the short-acting opioid remifentanil in male rats.

PubMed

Hofford, Rebecca S; Chow, Jonathan J; Beckmann, Joshua S; Bardo, Michael T

2017-12-01

Opioid abuse is a major problem around the world. Identifying environmental factors that contribute to opioid abuse and addiction is necessary for decreasing this epidemic. In rodents, environmental enrichment protects against the development of low dose stimulant self-administration, but studies examining the effect of enrichment and isolation (compared to standard housing) on the development of intravenous opioid self-administration have not been conducted. The present study investigated the role of environmental enrichment on self-administration of the short-acting μ-opioid remifentanil. Rats were raised in an enriched condition (Enr), standard condition (Std), or isolated condition (Iso) beginning at 21 days of age and were trained to lever press for 1 or 3 μg/kg/infusion remifentanil in young adulthood. Acquisition of self-administration and responding during increasing fixed ratio requirements were assessed, and a dose-response curve was generated. In all phases, Enr rats lever pressed significantly less than Std and Iso rats, with Enr rats pressing between 9 and 40% the amount of Iso rats. Enr rats did not acquire remifentanil self-administration when trained with 1 μg/kg/infusion, did not increase responding over increasing FR when trained at either dose, and their dose-response curves were flattened compared to Std and Iso rats. When expressed as economic demand curves, Enr rats displayed a decrease in both essential value (higher α) and reinforcer intensity (Q 0 ) compared to Std and Iso rats at the 1 μg/kg/infusion training dose. Environmental enrichment reduced remifentanil intake, suggesting that social and environmental novelty may protect against opioid abuse.

mGluR5 antagonist MPEP reduces ethanol-seeking and relapse behavior.

PubMed

Bäckström, Pia; Bachteler, Daniel; Koch, Sabrina; Hyytiä, Petri; Spanagel, Rainer

2004-05-01

The glutamatergic system plays an important role in mediating neurobehavioral effects of ethanol. Metabotropic glutamate receptors subtype 5 (mGluR5) are modulators of glutamatergic neurotransmission and are abundant in brain regions known to be involved in ethanol self-administration. Here, we studied the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a highly potent, noncompetitive mGlu5 receptor antagonist, on voluntary ethanol consumption and relapse behavior. For this purpose, we used two models for the measurement of relapse behavior: (i) reinstatement of ethanol-seeking behavior by drug-associated cues and (ii) the alcohol deprivation effect in long-term ethanol-consuming rats. In the first set of experiments, rats were trained to lever press for ethanol in the presence of a distinct set of cues. After extinction, the animals were exposed to the respective cues that initiated reinstatement of responding. A response-contingent ethanol prime further enhanced responding compared to the conditioned cues alone. Under these conditions, MPEP (0, 1, 3, and 10 mg/kg) attenuated ethanol seeking significantly and in a dose-related manner. However, at the highest dose, MPEP also decreased the number of inactive lever responses. In the second set of experiments, rats with 1 year of ethanol experience and repeated deprivation phases were used. A subchronic treatment with MPEP (twice daily; 0, 3, and 10 mg/kg) resulted in a significant and dose-dependent reduction of the alcohol deprivation effect (ADE). Although the same MPEP treatment regimen decreased baseline drinking, this effect was not as pronounced as on the ADE. These results show in two commonly used models of relapse to ethanol that pharmacological targeting of mGlu5 receptors may be a promising approach for the treatment of alcoholism.

Effect of sucrose availability on wheel-running as an operant and as a reinforcing consequence on a multiple schedule: Additive effects of extrinsic and automatic reinforcement.

PubMed

Belke, Terry W; Pierce, W David

2015-07-01

As a follow up to Belke and Pierce's (2014) study, we assessed the effects of repeated presentation and removal of sucrose solution on the behavior of rats responding on a two-component multiple schedule. Rats completed 15 wheel turns (FR 15) for either 15% or 0% sucrose solution in the manipulated component and lever pressed 10 times on average (VR 10) for an opportunity to complete 15 wheel turns (FR 15) in the other component. In contrast to our earlier study, the components advanced based on time (every 8min) rather than completed responses. Results showed that in the manipulated component wheel-running rates were higher and the latency to initiate running longer when sucrose was present (15%) compared to absent (0% or water); the number of obtained outcomes (sucrose/water), however, did not differ with the presentation and withdrawal of sucrose. For the wheel-running as reinforcement component, rates of wheel turns, overall lever-pressing rates, and obtained wheel-running reinforcements were higher, and postreinforcement pauses shorter, when sucrose was present (15%) than absent (0%) in manipulated component. Overall, our findings suggest that wheel-running rate regardless of its function (operant or reinforcement) is maintained by automatically generated consequences (automatic reinforcement) and is increased as an operant by adding experimentally arranged sucrose reinforcement (extrinsic reinforcement). This additive effect on operant wheel-running generalizes through induction or arousal to the wheel-running as reinforcement component, increasing the rate of responding for opportunities to run and the rate of wheel-running per opportunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Oscillator circuit for use with high loss quartz resonator sensors

DOEpatents

Wessendorf, Otto

1995-01-01

The disclosure is directed to a Lever oscillator for use in high resistance resonator applications, especially for use with quartz resonator sensors. The oscillator is designed to operate over a wide dynamic range of resonator resistance due to damping of the resonator in mediums such as liquids. An oscillator design is presented that allows both frequency and loss (R.sub.m) of the resonator to be determined over a wide dynamic range of resonator loss. The Lever oscillator uses negative feedback in a differential amplifier configuration to actively and variably divide (or leverage) the resonator impedance such that the oscillator can maintain the phase and gain of the loop over a wide range of resonator resistance.

16. OPERATOR STAND. OPERATOR STOOD BETWEEN RAILINGS AND CONTROLLED DREDGING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

16. OPERATOR STAND. OPERATOR STOOD BETWEEN RAILINGS AND CONTROLLED DREDGING OPERATIONS USING TWO LEVERS FROM CEILING, THREE LEVELS ON THE FLOOR, AND TWO FLOOR PEDDLES. RIGHT HAND CONTROLLED SHOT GUN SWINGER (BOOM MOVE TO RIGHT WHEN PUSHED FORWARD, LEFT WHEN PULLED BACK, AND, IF LUCKY, STOPPED WHEN IN CENTER POSITION). LEFT HAND CONTROLLED THROTTLE. FLOOR LEVER AND FLOOR PEDDLE ON LEFT CONTROLLED THE BACKING LINE FRICTION. MIDDLE LEVER AND PEDDLE, STUCK IN FLOOR CONTROLLED THE MAIN HOIST FRICTION. LEVER ON RIGHT CONTROLLED THE CYLINDER DRAIN VALVE. - Dredge CINCINNATI, Docked on Ohio River at foot of Lighthill Street, Pittsburgh, Allegheny County, PA

Ergonomic Evaluation of Space Shuttle Light-Weight Seat Lever Position and Operation

NASA Technical Reports Server (NTRS)

Maida, J.; Rajulu, Sudhakar L.; Bond, Robert L. (Technical Monitor)

2000-01-01

During a Shuttle flight in the early part of 1999, one of the crewmembers was unable to operate the backrest lever for the light-weight seat in microgravity. It is essential that the crewmembers are able to adjust this back-rest lever, which is titled forward 2 degrees from vertical during launch and then moved backwards to 10 degrees aft of vertical upon reaching orbit. This adjustment is needed to cushion the crewmembers during an inadvertent crash landing situation. The original Shuttle seats, which had seat controls located on the front left and right sides of the seat, were replaced recently with the new light-weight seats. The controls for these new, seats were moved to the night side with one control at the front and the other at the back. While it was uncertain whether the problem encountered was unique to that crewmember or not it was clear to the personnel responsible for maintaining the Shuttle seats that not knowing the cause of the problem posed a safety concern for NASA. Hence the Anthropometry and Biomechanics Facility (ABF) of the Johnson Space Center was requested to perform an evaluation of the seat controls and provide NASA with appropriate recommendations on whether the seat lever positions and operations should be modified. The ABF designed an experiment to investigate the amount of pull force exerted by subjects, wearing an unpressurized or pressurized crew launch escape suit, when controls were placed in the front and back (on the right side) of the light-weight seat. Single-axis load cells were attached to the seat levers, which measured the maximum static pull forces that were exerted by the subjects. Twelve subjects, six male and six female, participated in this study. Each subject was asked to perform the pull test at least three times for each combination of lever position and suit pressure conditions. The results from this study showed that as a whole (or in general), the subjects were able to pull on the lever at the back position with only about half the amount of force that they were able to exert on the lever at the front position. In addition, the results also showed that subjects wearing the pressurized suit were unable to reach the seat lever when it was located at the back. Furthermore, the pull forces on the front lever diminished about 50 % when subjects wore the pressurized suits. Based on these results from this study, it was recommended to NASA that the levers should not be located in the back position. In addition, further investigation is needed on whether the levers at the front of the seat could be modified or adjusted to increase the leverage for crew members wearing pressurized launch/escape suits.

Contextual control of instrumental actions and habits

PubMed Central

Thrailkill, Eric A.; Bouton, Mark E.

2014-01-01

After a relatively small amount of training, instrumental behavior is thought to be an action under the control of the motivational status of its goal or reinforcer. After more extended training, behavior can become habitual and insensitive to changes in reinforcer value. Recently, instrumental responding has been shown to weaken when tested outside of the training context. The present experiments compared the sensitivity of instrumental responding in rats to a context switch after training procedures that might differentially generate actions or habits. In Experiment 1, lever pressing was decremented in a new context after either short, medium, or long periods of training on either random-ratio or yoked random-interval reinforcement schedules. Experiment 2 found that more minimally-trained responding was also sensitive to a context switch. Moreover, Experiment 3 showed that when the goal-directed component of responding was removed by devaluing the reinforcer, the residual responding that remained was still sensitive to the change of context. Goal-directed responding, in contrast, transferred across contexts. Experiment 4 then found that after extensive training, a habit that was insensitive to reinforcer devaluation was still decremented by a context switch. Overall, the results suggest that a context switch primarily influences instrumental habit rather than action. In addition, even a response that has received relatively minimal training may have a habit component that is insensitive to reinforcer devaluation but sensitive to the effects of a context switch. PMID:25706547

Mechanical efficiency of two commercial lever-propulsion mechanisms for manual wheelchair locomotion.

PubMed

Lui, Jordon; MacGillivray, Megan K; Sheel, A William; Jeyasurya, Jeswin; Sadeghi, Mahsa; Sawatzky, Bonita Jean

2013-01-01

The purpose of this study was to (1) evaluate the mechanical efficiency (ME) of two commercially available lever-propulsion mechanisms for wheelchairs and (2) compare the ME of lever propulsion with hand rim propulsion within the same wheelchair. Of the two mechanisms, one contained a torsion spring while the other used a roller clutch design. We hypothesized that the torsion spring mechanism would increase the ME of propulsion due to a passive recovery stroke enabled by the mechanism. Ten nondisabled male participants with no prior manual wheeling experience performed submaximal exercise tests using both lever-propulsion mechanisms and hand rim propulsion on two different wheelchairs. Cardiopulmonary parameters including oxygen uptake (VO2), heart rate (HR), and energy expenditure (En) were determined. Total external power (Pext) was measured using a drag test protocol. ME was determined by the ratio of Pext to En. Results indicated no significant effect of lever-propulsion mechanism for all physiological measures tested. This suggests that the torsion spring did not result in a physiological benefit compared with the roller clutch mechanism. However, both lever-propulsion mechanisms showed decreased VO2 and HR and increased ME (as a function of slope) compared with hand rim propulsion (p < 0.001). This indicates that both lever-propulsion mechanisms tested are more mechanically efficient than conventional hand rim propulsion, especially when slopes are encountered.

Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice☆

PubMed Central

Salling, Michael C.; Hodge, Christopher J.; Psilos, Kelly E.; Eastman, Vallari R.; Faccidomo, Sara P.; Hodge, Clyde W.

2018-01-01

Cue-induced reinstatement of alcohol-seeking is a hallmark behavioral pathology of addiction. Evidence suggests that reinstatement (e.g., relapse), may be regulated by cell signaling systems that underlie neuroplasticity. A variety of plasticity events require activation of calcium calmodulin-dependent protein kinase II (CaMKII) in components of the reward pathway, such as the nucleus accumbens and amygdala. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior is associated with changes in the activation state (e.g., phosphorylation) of CaMKII-T286. Male C57BL/6J mice (n = 14) were trained to lever press on a fixed-ratio-4 schedule of sweetened alcohol (2% sucrose + 9% EtOH) reinforcement. After 14-d of extinction (no cues or reinforcers), mice underwent a response-contingent reinstatement (n = 7) vs. an additional day of extinction (n = 7). Brains were removed immediately after the test and processed for evaluation of pCaMKII-T286 immunoreactivity (IR). Number of pCaMKII-T286 positive cells/mm2 was quantified from coronal brain sections using Bioquant Image Analysis software. Mice emitted significantly more responses on the alcohol vs. the inactive lever throughout the baseline phase with average alcohol intake of 1.1 ± 0.03 g/kg/1-h. During extinction, responses on the alcohol lever decreased to inactive lever levels by day 7. Significant cue-induced reinstatement of alcohol-seeking was observed during a single test with no effects on the inactive lever. Reinstatement was associated with increased pCaMKII-T286 IR specifically in amygdala (LA and BLA), nucleus accumbens (AcbSh), lateral septum, mediodorsal thalamus, and piriform cortex as compared to extinction control. Brain regions showing no change included the dorsal striatum, medial septum, cingulate cortex, habenula, paraventricular thalamus, and ventral hypothalamus. These results show response contingent cue-induced reinstatement of alcohol-seeking behavior is associated with selective increases in pCaMKII-T286 in specific reward- and memory-related brain regions of male C57BL/6J mice. Primary molecular mechanisms of associative learning and memory may regulate relapse in alcohol addiction. PMID:29100991

Seeking behavior, place conditioning, and resistance to conditioned suppression of feeding in rats intermittently exposed to palatable food.

PubMed

Velázquez-Sánchez, Clara; Santos, Jeffrey W; Smith, Karen L; Ferragud, Antonio; Sabino, Valentina; Cottone, Pietro

2015-04-01

Binge eating disorder is characterized by excessive consumption of highly palatable food within short periods of time accompanied by loss of control over eating. Extensive evidence provides support for the consideration of binge eating disorder as an addiction-like disorder. In this study, we wanted to determine whether rats undergoing an operant binge-like eating procedure could develop maladaptive forms of conditioned feeding behaviors. For this purpose, we trained male rats to self-administer either a sugary, highly palatable diet ("Palatable" rats) or a chow diet ("Chow" rats) for 1 hour a day. After escalation and stabilization of palatable food intake, we tested Chow and Palatable rats in (a) a conditioned place preference test, (b) a second-order schedule of reinforcement, (c) a cue-induced suppression of feeding test. In the conditioned place preference task, Palatable rats spent significantly more time in the compartment that was previously paired with the palatable food, compared to Chow controls. Furthermore, in the second-order schedule of reinforcement task, Palatable rats exhibited active lever responding 4- to 6-fold higher than Chow control rats. Finally, in the cue-induced suppression of feeding test, although Chow control subjects reduced responding by 32% in the presence of the conditioned punishment, Palatable rats persevered in responding despite the aversive cue. These results further characterize this animal model of binge-like eating and provide additional evidence for the addictive properties of highly palatable food. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Chemogenetic manipulation of ventral pallidal neurons impairs acquisition of sign-tracking in rats.

PubMed

Chang, Stephen E; Todd, Travis P; Bucci, David J; Smith, Kyle S

2015-12-01

Cues associated with rewarding events acquire value themselves as a result of the incentive value of the reward being transferred to the cue. Consequently, presentation of a reward-paired cue can trigger reward-seeking behaviours towards the cue itself (i.e. sign-tracking). The ventral pallidum (VP) has been demonstrated to be involved in a number of motivated behaviours, both conditioned and unconditioned. However, its contribution to the acquisition of incentive value is unknown. Using a discriminative autoshaping procedure with levers, the effects of disrupting VP activity in rats on the emergence of sign-tracking was investigated using chemogenetics, i.e. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Transient disruption of VP neurons [activation of the inhibitory hM4D(Gi) DREADD through systemic injections of clozapine N-oxide (CNO) prior to each autoshaping session] impaired acquisition of sign-tracking (lever press rate) without having any effect on approach to the site of reward delivery (i.e. goal-tracking) or on the expression of sign-tracking after it was acquired. In addition, electrophysiological recordings were conducted in freely behaving rats following VP DREADD activation. The majority of VP units that were responsive to CNO injections exhibited rapid inhibition relative to baseline, a subset of CNO-responsive units showed delayed excitation, and a smaller subset displayed a mixed response of inhibition and excitation following CNO injections. It is argued that disruption of VP during autoshaping specifically disrupted the transfer of incentive value that was attributed to the lever cue, suggesting a surprisingly fundamental role for the VP in acquiring, compared with expressing, Pavlovian incentive values. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The attribution of incentive salience to Pavlovian alcohol cues: a shift from goal-tracking to sign-tracking

PubMed Central

Srey, Chandra S.; Maddux, Jean-Marie N.; Chaudhri, Nadia

2015-01-01

Environmental stimuli that are reliably paired with alcohol may acquire incentive salience, a property that can operate in the use and abuse of alcohol. Here we investigated the incentive salience of Pavlovian alcohol cues using a preclinical animal model. Male, Long-Evans rats (Harlan) with unrestricted access to food and water were acclimated to drinking 15% ethanol (v/v) in their home-cages. Rats then received Pavlovian autoshaping training in which the 10 s presentation of a retractable lever served as the conditioned stimulus (CS) and 15% ethanol served as the unconditioned stimulus (US) (0.2 ml/CS; 12 CS presentations/session; 27 sessions). Next, in an operant test of conditioned reinforcement, nose pokes into an active aperture delivered presentations of the lever-CS, whereas nose pokes into an inactive aperture had no consequences. Across initial autoshaping sessions, goal-tracking behavior, as measured by entries into the fluid port where ethanol was delivered, developed rapidly. However, with extended training goal-tracking diminished, and sign-tracking responses, as measured by lever-CS activations, emerged. Control rats that received explicitly unpaired CS and US presentations did not show goal-tracking or sign-tracking responses. In the test for conditioned reinforcement, rats with CS-US pairings during autoshaping training made more active relative to inactive nose pokes, whereas rats in the unpaired control group did not. Moreover, active nose pokes were positively correlated with sign-tracking behavior during autoshaping. Extended training may produce a shift in the learned properties of Pavlovian alcohol cues, such that after initially predicting alcohol availability they acquire robust incentive salience. PMID:25784867

Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors.

PubMed

Nemirovsky, Sergio I; Avale, M Elena; Brunner, Daniela; Rubinstein, Marcelo

2009-11-01

The dopamine D4 receptor (D4R) is predominantly expressed in the prefrontal cortex, a brain area that integrates motor, rewarding, and cognitive information. Because participation of D4Rs in executive learning is largely unknown, we challenged D4R knockout mice (Drd4(-/-)) and their wild-type (WT) littermates, neonatally treated with 6-hydroxydopamine (6-OHDA; icv) or vehicle in two operant learning paradigms. A continuous reinforcement task, in which one food-pellet was delivered after every lever press, showed that 6-OHDA-treated mice (hypodopaminergic) WT mice pressed the reinforcing lever at much lower rates than normodopaminergic WT mice. In contrast, Drd4(-/-) mice displayed increased lever pressing rates, regardless of their dopamine content. In another study, mice were trained to solve an operant two-choice task in which a first showing lever was coupled to the delivery of one food pellet only after a second lever emerged. Interval between presentation of both levers was initially 12 s and progressively shortened to 6, 2, and finally 0.5 s. Normodopaminergic WT mice obtained a pellet reward in more than 75% of the trials at 12, 6, and 2 s, whereas hypodopaminergic WT mice were severely impaired to select the reward-paired lever. Absence of D4Rs was not detrimental in this task. Moreover, hypodopaminergic Drd4(-/-) mice were as efficient as their normodopaminergic Drd4(-/-) siblings in selecting the reward-paired lever. In summary, hypodopaminergic mice exhibit severe impairments to retrieve rewards in two operant positive reinforcement tasks, but these deleterious effects are totally prevented in the absence of functional D4Rs.

The precision and torque production of common hip adductor squeeze tests used in elite football.

PubMed

Light, N; Thorborg, K

2016-11-01

Decreased hip adductor strength is a known risk factor for groin injury in footballers, with clinicians testing adductor strength in various positions and using different protocols. Understanding how reliable and how much torque different adductor squeeze tests produce will facilitate choosing the most appropriate method for future testing. In this study, the reliability and torque production of three common adductor squeeze tests were investigated. Test-retest reliability and cross-sectional comparison. Twenty elite level footballers (16-33 years) without previous or current groin pain were recruited. Relative and absolute test-retest reliability, and torque production of three adductor squeeze tests (long-lever in abduction, short-lever in adduction and short-lever in abduction/external rotation) were investigated. Each participant performed a series of isometric strength tests measured by hand-held dynamometry in each position, on two test days separated by two weeks. No systematic variation was seen for any of the tests when using the mean of three measures (ICC=0.84-0.97, MDC%=6.6-19.5). The smallest variation was observed when taking the mean of three repetitions in the long-lever position (ICC=0.97, MDC%=6.6). The long-lever test also yielded the highest mean torque values, which were 69% and 11% higher than the short-lever in adduction test and short-lever in abduction/external rotation test respectively (p<0.001). All three tests described in this study are reliable methods of measuring adductor squeeze strength. However, the test performed in the long-lever position seems the most promising as it displays high test-retest precision and the highest adductor torque production. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Aripiprazole blocks reinstatement of cocaine seeking in an animal model of relapse.

PubMed

Feltenstein, Matthew W; Altar, C Anthony; See, Ronald E

2007-03-01

Aripiprazole (Abilify) is an atypical antipsychotic drug primarily characterized by partial agonist activity at dopamine (DA) D2 receptors and low side effects. Based on pharmacologic properties that include a stabilization of mesocorticolimbic DA activity, a pathway implicated in addiction, aripiprazole was tested for its ability to prevent relapse to cocaine seeking in rats. We assessed the dose-dependent effects of aripiprazole on conditioned cue-induced and cocaine-primed reinstatement of drug-seeking behavior following chronic intravenous cocaine self-administration in an animal model of relapse. Aripiprazole potently and dose-dependently attenuated responding on the previously cocaine-paired lever during both reinstatement conditions, with slightly greater efficacy at reducing conditioned-cued reinstatement. Aripiprazole was effective at doses that failed to alter cocaine self-administration, food self-administration, reinstatement of food-seeking behavior, or basal locomotor activity, suggesting selective effects of aripiprazole on motivated drug-seeking behavior. These results in a relapse model show that aripiprazole can block cocaine seeking without affecting other behaviors. The D2 partial agonist properties of aripiprazole likely account for the blockade of reinstatement of cocaine-seeking behavior. Given its established efficacy and tolerability as a treatment for psychosis, aripiprazole may be an excellent therapeutic choice for reducing craving and preventing relapse in people with cocaine dependency.

Enhanced incentive motivation for sucrose-paired cues in adolescent rats: possible roles for dopamine and opioid systems.

PubMed

Burton, Christie L; Noble, Kevin; Fletcher, Paul J

2011-07-01

Vulnerability to the effects of drugs of abuse during adolescence may be related to altered incentive motivation, a process believed to be important in addiction. Incentive motivation can be seen when a neutral stimulus acquires motivational properties through repeated association with a primary reinforcer. We compared adolescent (postnatal day (PND) 24-50) and adult (>PND 70) rats on a measure of incentive motivation: responding for a conditioned reinforcer (CR). Rats learned to associate the delivery of 0.1 ml of 10% sucrose with a conditioned stimulus (CS; light and tone); 30 pairings per day were given over 14 days. Then, we measured responding on a lever delivering the CS (now a CR) after injections of amphetamine (0, 0.25 or 0.5 mg/kg). We also examined responding for CR when the CS and sucrose were paired or unpaired during conditioning, and responding for the primary reinforcer (10% sucrose) in control experiments. Finally, we examined the effects of D(1) and D(2) dopamine receptor antagonists (SCH 39166 and eticlopride, respectively) and an opioid receptor antagonist (naltrexone) on responding for a CR in adolescent rats. Adolescents but not adults acquired responding for a CR, but adolescents responded less than adults for the primary reinforcer. Responding for a CR depended upon the pairing of the CS and sucrose during conditioning. Both dopamine and opioid receptor antagonists reduced responding for the CR. Therefore, incentive motivation may be enhanced in adolescents compared with adults, and incentive motivation may be mediated in part by both dopamine and opioid systems.

The endogenous cannabinoid anandamide shares discriminative stimulus effects with ∆(9)-tetrahydrocannabinol in fatty acid amide hydrolase knockout mice.

PubMed

Walentiny, D Matthew; Gamage, Thomas F; Warner, Jonathan A; Nguyen, Thanh K; Grainger, Darren B; Wiley, Jenny L; Vann, Robert E

2011-04-10

The endogenous cannabinoid system has been noted for its therapeutic potential, as well as the psychoactivity of cannabinoids such as Δ9-tetrahydrocannabinol (THC). However, less is known about the psychoactivity of anandamide (AEA), an endocannabinoid ligand. Thus, the goals of this study were to establish AEA as a discriminative stimulus in transgenic mice lacking fatty acid amide hydrolase (i.e., FAAH -/- mice unable to rapidly metabolize AEA), evaluate whether THC or oleamide, a fatty acid amide, produced AEA-like responding, and assess for CB(1) mediation of AEA's discriminative stimulus. Mice readily discriminated between 6mg/kg AEA and vehicle in a two-lever drug discrimination task. AEA dose-dependently generalized to itself. THC elicited full AEA-like responding, whereas oleamide failed to substitute. The CB(1) antagonist rimonabant attenuated AEA- and THC-induced AEA-appropriate responding, demonstrating CB(1) mediation of AEA's discriminative stimulus. These findings suggest that, in the absence of FAAH, AEA produces intoxication comparable to THC, and consequently to marijuana. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of long-term shock and associated stimuli on aggressive and manual responses1

PubMed Central

Hutchinson, R. R.; Renfrew, J. W.; Young, G. A.

1971-01-01

Squirrel monkeys were exposed to response-independent, fixed-frequency shock that produced biting attack upon a pneumatic hose. Attacks decreased within and across sessions at low intensities and high frequencies of shock, but increased within and across sessions at higher intensities and lower shock frequencies. Stimuli paired with shock, when presented alone, came to produce biting, and stimuli correlated with shock parameters that produced increases in responding within sessions produced similar increases when presented alone. Further experiments showed that continuing exposure to shock also produced lever pressing or chain pulling, with longer shock exposure again producing higher response rates. Whereas biting generally decreased throughout the intershock interval, manual responding generally increased as shock time approached, but immediately before shock was often suppressed. Following shock, biting attack predominated over manual behavior. The results suggest a possible explanation for the extreme resistance of avoidance behavior to extinction, and may also partially explain the persistence of responding during schedules of response-produced shock. Relationships of the present findings to naturalistic observations of relations between fleeing, freezing, and fighting performances are discussed. PMID:16811496

Noninvasive determination of optical lever sensitivity in atomic force microscopy

NASA Astrophysics Data System (ADS)

Higgins, M. J.; Proksch, R.; Sader, J. E.; Polcik, M.; Mc Endoo, S.; Cleveland, J. P.; Jarvis, S. P.

2006-01-01

Atomic force microscopes typically require knowledge of the cantilever spring constant and optical lever sensitivity in order to accurately determine the force from the cantilever deflection. In this study, we investigate a technique to calibrate the optical lever sensitivity of rectangular cantilevers that does not require contact to be made with a surface. This noncontact approach utilizes the method of Sader et al. [Rev. Sci. Instrum. 70, 3967 (1999)] to calibrate the spring constant of the cantilever in combination with the equipartition theorem [J. L. Hutter and J. Bechhoefer, Rev. Sci. Instrum. 64, 1868 (1993)] to determine the optical lever sensitivity. A comparison is presented between sensitivity values obtained from conventional static mode force curves and those derived using this noncontact approach for a range of different cantilevers in air and liquid. These measurements indicate that the method offers a quick, alternative approach for the calibration of the optical lever sensitivity.

Levers and Mixtures: An Integrated Science and Mathematics Activity to Solve Problems

ERIC Educational Resources Information Center

Alpaslan, Muhammet Mustafa

2017-01-01

In recent years, the integration of science and mathematics has become popular among educators because of its potential benefits for student learning. The purpose of this study is to introduce a two-day interdisciplinary lesson that brings science and mathematics concepts together, actively engaging students in working with percentages of the…

The dopamine D2/D3 receptor agonist quinpirole increases checking-like behaviour in an operant observing response task with uncertain reinforcement: a novel possible model of OCD.

PubMed

Eagle, Dawn M; Noschang, Cristie; d'Angelo, Laure-Sophie Camilla; Noble, Christie A; Day, Jacob O; Dongelmans, Marie Louise; Theobald, David E; Mar, Adam C; Urcelay, Gonzalo P; Morein-Zamir, Sharon; Robbins, Trevor W

2014-05-01

Excessive checking is a common, debilitating symptom of obsessive-compulsive disorder (OCD). In an established rodent model of OCD checking behaviour, quinpirole (dopamine D2/3-receptor agonist) increased checking in open-field tests, indicating dopaminergic modulation of checking-like behaviours. We designed a novel operant paradigm for rats (observing response task (ORT)) to further examine cognitive processes underpinning checking behaviour and clarify how and why checking develops. We investigated i) how quinpirole increases checking, ii) dependence of these effects on D2/3 receptor function (following treatment with D2/3 receptor antagonist sulpiride) and iii) effects of reward uncertainty. In the ORT, rats pressed an 'observing' lever for information about the location of an 'active' lever that provided food reinforcement. High- and low-checkers (defined from baseline observing) received quinpirole (0.5mg/kg, 10 treatments) or vehicle. Parametric task manipulations assessed observing/checking under increasing task demands relating to reinforcement uncertainty (variable response requirement and active-lever location switching). Treatment with sulpiride further probed the pharmacological basis of long-term behavioural changes. Quinpirole selectively increased checking, both functional observing lever presses (OLPs) and non-functional extra OLPs (EOLPs). The increase in OLPs and EOLPs was long-lasting, without further quinpirole administration. Quinpirole did not affect the immediate ability to use information from checking. Vehicle and quinpirole-treated rats (VEH and QNP respectively) were selectively sensitive to different forms of uncertainty. Sulpiride reduced non-functional EOLPs in QNP rats but had no effect on functional OLPs. These data have implications for treatment of compulsive checking in OCD, particularly for serotonin-reuptake-inhibitor treatment-refractory cases, where supplementation with dopamine receptor antagonists may be beneficial. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Error analysis and correction of lever-type stylus profilometer based on Nelder-Mead Simplex method

NASA Astrophysics Data System (ADS)

Hu, Chunbing; Chang, Suping; Li, Bo; Wang, Junwei; Zhang, Zhongyu

2017-10-01

Due to the high measurement accuracy and wide range of applications, lever-type stylus profilometry is commonly used in industrial research areas. However, the error caused by the lever structure has a great influence on the profile measurement, thus this paper analyzes the error of high-precision large-range lever-type stylus profilometry. The errors are corrected by the Nelder-Mead Simplex method, and the results are verified by the spherical surface calibration. It can be seen that this method can effectively reduce the measurement error and improve the accuracy of the stylus profilometry in large-scale measurement.

Three-axis lever actuator with flexure hinges for an optical disk system

NASA Astrophysics Data System (ADS)

Han, Chang-Soo; Kim, Soo-Hyun

2002-10-01

A three-axis lever actuator with a flexure hinge has been designed and fabricated. This actuator is driven by electromagnetic force based on a coil-magnet system and can be used as a high precision actuator and, especially as a pickup head actuator in optical disks. High precision and low sensitivity to external vibration are the major advantages of this lever actuator. An analysis model was found and compared to the finite element method. Dynamic characteristics of the three-axis lever actuator were measured. The results are in very close agreement to those predicted by the model and finite element analysis.

Hard turning micro-machine tool

DOEpatents

DeVor, Richard E; Adair, Kurt; Kapoor, Shiv G

2013-10-22

A micro-scale apparatus for supporting a tool for hard turning comprises a base, a pivot coupled to the base, an actuator coupled to the base, and at least one member coupled to the actuator at one end and rotatably coupled to the pivot at another end. A tool mount is disposed on the at least one member. The at least one member defines a first lever arm between the pivot and the tool mount, and a second lever arm between the pivot and the actuator. The first lever arm has a length that is less than a length of the second lever arm. The actuator moves the tool mount along an arc.

A Lever Coupling Mechanism in Dual-Mass Micro-Gyroscopes for Improving the Shock Resistance along the Driving Direction.

PubMed

Gao, Yang; Li, Hongsheng; Huang, Libin; Sun, Hui

2017-04-30

This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope's modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity.

DEVICE FOR CONTROL OF OXYGEN PARTIAL PRESSURE

DOEpatents

Bradner, H.; Gordon, H.S.

1957-12-24

A device is described that can sense changes in oxygen partial pressure and cause a corresponding mechanical displacement sufficient to actuate meters, valves and similar devices. A piston and cylinder arrangement contains a charge of crystalline metal chelate pellets which have the peculiar property of responding to variations in the oxygen content of the ambient atmosphere by undergoing a change in dimension. A lever system amplifies the relative displacement of the piston in the cylinder, and actuates the controlled valving device. This partial pressure oxygen sensing device is useful in controlled chemical reactions or in respiratory devices such as the oxygen demand meters for high altitude aircraft.

Handwriting as an operant1

PubMed Central

Gonzalez, Fernando A.; Waller, Marcus B.

1974-01-01

An apparatus was designed to monitor handwriting behavior. Two subjects were studied under various schedules of monetary reinforcement for handwriting. The different schedules engendered and maintained distinctive response patterns but the rates of sustained responding did not vary across schedules. The development of fixed-interval performance following continuous reinforcement resembled the same transition in lower animals. In one subject, availability of reading material interacted with the schedule to determine response pattern. It was suggested that handwriting may be a more appropriate response for the experimental analysis of human behavior than the more frequently used button-pushing or lever-pulling responses. ImagesFig. 1.Fig. 2. PMID:16811729

Fueling innovation in medical devices (and beyond): venture capital in health care.

PubMed

Ackerly, D Clay; Valverde, Ana M; Diener, Lawrence W; Dossary, Kristin L; Schulman, Kevin A

2009-01-01

Innovation in health care requires new ideas and the capital to develop and commercialize those ideas into products or services. The necessary capital is often "venture capital," but the link between public policy and the venture capital industry has not been well examined. In this paper we explore the link between venture capital and innovation in health care, and we present new descriptive data from a survey of health care venture capital fund managers. Respondents generally viewed policy levers (for example, reimbursement and regulations) as important risks to venture capital investments, potentially affecting their ability to raise capital for early-stage investment funds.

Nucleus Accumbens Core and Shell Differentially Encode Reward-Associated Cues after Reinforcer Devaluation

PubMed Central

West, Elizabeth A.

2016-01-01

Nucleus accumbens (NAc) neurons encode features of stimulus learning and action selection associated with rewards. The NAc is necessary for using information about expected outcome values to guide behavior after reinforcer devaluation. Evidence suggests that core and shell subregions may play dissociable roles in guiding motivated behavior. Here, we recorded neural activity in the NAc core and shell during training and performance of a reinforcer devaluation task. Long–Evans male rats were trained that presses on a lever under an illuminated cue light delivered a flavored sucrose reward. On subsequent test days, each rat was given free access to one of two distinctly flavored foods to consume to satiation and were then immediately tested on the lever pressing task under extinction conditions. Rats decreased pressing on the test day when the reinforcer earned during training was the sated flavor (devalued) compared with the test day when the reinforcer was not the sated flavor (nondevalued), demonstrating evidence of outcome-selective devaluation. Cue-selective encoding during training by NAc core (but not shell) neurons reliably predicted subsequent behavioral performance; that is, the greater the percentage of neurons that responded to the cue, the better the rats suppressed responding after devaluation. In contrast, NAc shell (but not core) neurons significantly decreased cue-selective encoding in the devalued condition compared with the nondevalued condition. These data reveal that NAc core and shell neurons encode information differentially about outcome-specific cues after reinforcer devaluation that are related to behavioral performance and outcome value, respectively. SIGNIFICANCE STATEMENT Many neuropsychiatric disorders are marked by impairments in behavioral flexibility. Although the nucleus accumbens (NAc) is required for behavioral flexibility, it is not known how NAc neurons encode this information. Here, we recorded NAc neurons during a training session in which rats learned that a cue predicted a specific reward and during a test session when that reward value was changed. Although encoding in the core during training predicted the ability of rats to change behavior after the reward value was altered, the NAc shell encoded information about the change in reward value during the test session. These findings suggest differential roles of the core and shell in behavioral flexibility. PMID:26818502

Sleep restriction in rats leads to changes in operant behaviour indicative of reduced prefrontal cortex function.

PubMed

Kamphuis, Jeanine; Baichel, Swetlana; Lancel, Marike; de Boer, Sietse F; Koolhaas, Jaap M; Meerlo, Peter

2017-02-01

Sleep deprivation has profound effects on cognitive performance, and some of these effects may be mediated by impaired prefrontal cortex function. In search of an animal model to investigate this relationship we studied the influence of restricted sleep on operant conditioning in rats, particularly the performance in a differential reinforcement of low rate responding (DRL) task, which is highly dependent upon an intact prefrontal cortex. Animals were trained to withhold a lever press until an imposed delay of 30 s after the last press had passed in order to achieve a food reward. Once the animals had mastered the task, they were sleep-restricted for 7 days with 20 h of sleep deprivation per day. At the end of each daily sleep deprivation session, performance on the DRL task was assessed. The results show that sleep-restricted animals were less able to time their responses correctly, started pressing the lever more randomly and showed signs of behavioural disinhibition, the latter possibly reflecting enhanced impulsivity. Our data support the hypothesis that a sleep debt has disruptive consequences for the functioning of the prefrontal cortex. This model offers possibilities for future studies investigating the underlying biochemical and molecular mechanisms of this relationship. © 2016 European Sleep Research Society.

Dorsomedial striatum lesions affect adjustment to reward uncertainty, but not to reward devaluation or omission.

PubMed

Torres, Carmen; Glueck, Amanda C; Conrad, Shannon E; Morón, Ignacio; Papini, Mauricio R

2016-09-22

The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of sucrose availability and pre-running on the intrinsic value of wheel running as an operant and a reinforcing consequence.

PubMed

Belke, Terry W; Pierce, W David

2014-03-01

The current study investigated the effect of motivational manipulations on operant wheel running for sucrose reinforcement and on wheel running as a behavioral consequence for lever pressing, within the same experimental context. Specifically, rats responded on a two-component multiple schedule of reinforcement in which lever pressing produced the opportunity to run in a wheel in one component of the schedule (reinforcer component) and wheel running produced the opportunity to consume sucrose solution in the other component (operant component). Motivational manipulations involved removal of sucrose contingent on wheel running and providing 1h of pre-session wheel running. Results showed that, in opposition to a response strengthening view, sucrose did not maintain operant wheel running. The motivational operations of withdrawing sucrose or providing pre-session wheel running, however, resulted in different wheel-running rates in the operant and reinforcer components of the multiple schedule; this rate discrepancy revealed the extrinsic reinforcing effects of sucrose on operant wheel running, but also indicated the intrinsic reinforcement value of wheel running across components. Differences in wheel-running rates between components were discussed in terms of arousal, undermining of intrinsic motivation, and behavioral contrast. Copyright © 2013 Elsevier B.V. All rights reserved.

Levers for Change in Educational Development in Canada: Looking Back, Looking Forward

ERIC Educational Resources Information Center

Dawson, Debra L.

2017-01-01

This paper examines levers or drivers that have influenced the direction of educational development in Canada over the last 40 years and also tries to predict what will be the impact of some current levers on changing the work of developers in the next 20 years. Reflecting on those years, it is apparent our work in the 1980s was very focused on…

A Lever for Life: How I Lost 150 Pounds and Learned the Catalytic Power of School Community

ERIC Educational Resources Information Center

Ebner, Steven J.

2011-01-01

The quotation, attributed to the Greek mathematician Archimedes, about the power of levers to move the world has been quoted many times with slight variations, but usually the point is the same: "With the right lever, one can move the earth." However, the actual quotation attributed to Archimedes comes in the writings of another Greek…

Comparison of the effects of antipsychotic drugs on the schedule-controlled behavior of squirrel monkeys and pigeons.

PubMed

Barrett, J E

1983-04-01

Lever pressing by squirrel monkeys and key pecking by pigeons were maintained under a multiple 3-min fixed-interval (FI), 30-response fixed-ratio (FR) schedule by the presentation of food. These responses, which differed under the two schedules, but were similar for both species, were used to compare the effects of antipsychotic compounds from different pharmacological classes. Except for differences in potency levels, the effects of intermediate doses of haloperidol and molindone were similar in monkeys and pigeons; these compounds decreased responding under the fixed-interval schedule at doses that did not affect fixed-ratio responding. Similar effects also occurred with chlorpromazine, promazine and thiothixene in pigeons. With monkeys, however, intermediate doses of promazine decreased fixed-ratio responding more than responding maintained under the fixed-interval schedule, while chlorpromazine and thiothixene produced similar effects on responding under both schedules. The effects of novel antipsychotic, clozapine, differed from those of the other agents in both monkeys and pigeons. With both species clozapine increased fixed interval responding at doses that did not affect responding under the fixed-ratio schedule. Doses required to reduce responding at least 50% were approximately 5 to 160 times greater for pigeons than for monkeys for all drugs except clozapine which was equipotent in both species. In monkeys the order of potency was haloperidol greater than molindone = thiothixene greater than chlorpromazine greater than clozapine greater than promazine, whereas in pigeons the order was haloperidol greater than thiothixene greater than clozapine greater than molindone greater than promazine greater than chlorpromazine.

Intravenous alcohol self-administration in the P rat.

PubMed

Windisch, Kyle A; Kosobud, Ann E K; Czachowski, Cristine L

2014-08-01

Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally "relevant" effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding "non-pharmacological" effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol's effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol self-administration methodology cannot overcome the aversive properties of ethanol via this route in the rat. Copyright © 2014 Elsevier Inc. All rights reserved.

'Roid rage in rats? Testosterone effects on aggressive motivation, impulsivity and tyrosine hydroxylase.

PubMed

Wood, Ruth I; Armstrong, Abigail; Fridkin, Vlad; Shah, Vivek; Najafi, Allison; Jakowec, Michael

2013-02-17

In humans and animals, anabolic-androgenic steroids (AAS) increase aggression, but the underlying behavioral mechanisms are unclear. AAS may increase the motivation to fight. Alternatively, AAS may increase impulsive behavior, consistent with the popular image of 'roid rage. To test this, adolescent male rats were treated chronically with testosterone (7.5mg/kg) or vehicle and tested for aggressive motivation and impulsivity. Rats were trained to respond on a nose-poke on a 10 min fixed-interval schedule for the opportunity to fight in their home cage with an unfamiliar rat. Although testosterone increased aggression (6.3±1.3 fights/5 min vs 2.4±0.8 for controls, p<0.05), there was no difference in operant responding (28.4±1.6 nose-pokes/10 min for testosterone, 32.4±7.0 for vehicle). This suggests that testosterone does not enhance motivation for aggression. To test for impulsivity, rats were trained to respond for food in a delay-discounting procedure. In an operant chamber, one lever delivered one food pellet immediately, the other lever gave 4 pellets after a delay (0, 15, 30 or 45 s). In testosterone- and vehicle-treated rats, body weights and food intake did not differ. However, testosterone-treated rats chose the larger, delayed reward more often (4.5±0.7 times in 10 trials with 45 s delay) than vehicle controls (2.5±0.5 times, p<0.05), consistent with a reduction in impulsive choice. Thus, although chronic high-dose testosterone enhances aggression, this does not include an increase in impulsive behavior or motivation to fight. This is further supported by measurement of tyrosine hydroxylase (TH) by Western immunoblot analysis in brain regions important for motivation (nucleus accumbens, Acb) and executive function (medial prefrontal cortex, PFC). There were no differences in TH between testosterone- and vehicle-treated rats in Acb or PFC. However, testosterone significantly reduced TH (to 76.9±3.1% of controls, p<0.05) in the caudate-putamen, a brain area important for behavioral inhibition, motor control and habit learning. Copyright © 2013 Elsevier Inc. All rights reserved.

‘Roid rage in rats? Testosterone effects on aggressive motivation, impulsivity and tyrosine hydroxylase

PubMed Central

Wood, Ruth I.; Armstrong, Abigail; Fridkin, Vlad; Shah, Vivek; Najafi, Allison; Jakowec, Michael

2013-01-01

In humans and animals, anabolic-androgenic steroids (AAS) increase aggression, but the underlying behavioral mechanisms are unclear. AAS may increase the motivation to fight. Alternatively, AAS may increase impulsive behavior, consistent with the popular image of ‘roid rage. To test this, adolescent male rats were treated chronically with testosterone (7.5 mg/kg) or vehicle and tested for aggressive motivation and impulsivity. Rats were trained to respond on a nose-poke on a 10 min fixed-interval schedule for the opportunity to fight in their home cage with an unfamiliar rat. Although testosterone increased aggression (6.3±1.3 fights/5 min vs 2.4±0.8 for controls, p<0.05), there was no difference in operant responding (28.4±1.6 nose-pokes/ 10 min for testosterone, 32.4±7.0 for vehicle). This suggests that testosterone does not enhance motivation for aggression. To test for impulsivity, rats were trained to respond for food in a delay-discounting procedure. In an operant chamber, one lever delivered one food pellet immediately, the other lever gave 4 pellets after a delay (0, 15, 30 or 45 s). In testosterone- and vehicle-treated rats, body weights and food intake did not differ. However, testosterone-treated rats chose the larger, delayed reward more often (4.5±0.7 times in 10 trials with 45 s delay) than vehicle controls (2.5±0.5 times, p<0.05), consistent with a reduction in impulsive choice. Thus, although chronic high-dose testosterone enhances aggression, this does not include an increase in impulsive behavior or motivation to fight. This is further supported by measurement of tyrosine hydroxylase (TH) by Western immunoblot analysis in brain regions important for motivation (nucleus accumbens, Acb) and executive function (medial prefrontal cortex, PFC). There were no differences in TH between testosterone- and vehicle-treated rats in Acb or PFC. However, testosterone significantly reduced TH (to 76.9±3.1% of controls, p<0.05) in the caudate-putamen, a brain area important for behavioral inhibition, motor control and habit learning. PMID:23266798

INDEXING MECHANISM

DOEpatents

Kock, L.J.

1959-09-22

A device is presented for loading and unloading fuel elements containing material fissionable by neutrons of thermal energy. The device comprises a combination of mechanical features Including a base, a lever pivotally attached to the base, an Indexing plate on the base parallel to the plane of lever rotation and having a plurality of apertures, the apertures being disposed In rows, each aperture having a keyway, an Index pin movably disposed to the plane of lever rotation and having a plurality of apertures, the apertures being disposed in rows, each aperture having a keyway, an index pin movably disposed on the lever normal to the plane rotation, a key on the pin, a sleeve on the lever spaced from and parallel to the index pin, a pair of pulleys and a cable disposed between them, an open collar rotatably attached to the sleeve and linked to one of the pulleys, a pin extending from the collar, and a bearing movably mounted in the sleeve and having at least two longitudinal grooves in the outside surface.

[Equivalent Lever Principle of Ossicular Chain and Amplitude Reduction Effect of Internal Ear Lymph].

PubMed

Zhao, Xiaoyan; Qin, Renjia

2015-04-01

This paper makes persuasive demonstrations on some problems about the human ear sound transmission principle in existing physiological textbooks and reference books, and puts forward the authors' view to make up for its literature. Exerting the knowledge of lever in physics and the acoustics theory, we come up with an equivalent simplified model of manubrium mallei which is to meet the requirements as the long arm of the lever. We also set up an equivalent simplified model of ossicular chain--a combination of levers of ossicular chain. We disassemble the model into two simple levers, and make full analysis and demonstration on them. Through the calculation and comparison of displacement amplitudes in both external auditory canal air and internal ear lymph, we may draw a conclusion that the key reason, which the sound displacement amplitude is to be decreased to adapt to the endurance limit of the basement membrane, is that the density and sound speed in lymph is much higher than those in the air.

Pin-Retraction Mechanism On Quick-Release Cover

NASA Technical Reports Server (NTRS)

Macmartin, Malcolm

1994-01-01

Quick-release cover includes pin-retraction mechanism releasing cover quickly from lower of two sets of pin connections holding cover. Cover released at top by pulling lever as described in "Lever-Arm Pin Puller" (NPO-18788). Removal of cover begins when technician or robot pulls upper-pin-release lever. Cover swings downward until tabs on lower pins are pulled through slots in their receptacles. Lower pins are then free.

Speed-Selector Guard For Machine Tool

NASA Technical Reports Server (NTRS)

Shakhshir, Roda J.; Valentine, Richard L.

1992-01-01

Simple guardplate prevents accidental reversal of direction of rotation or sudden change of speed of lathe, milling machine, or other machine tool. Custom-made for specific machine and control settings. Allows control lever to be placed at only one setting. Operator uses handle to slide guard to engage or disengage control lever. Protects personnel from injury and equipment from damage occurring if speed- or direction-control lever inadvertently placed in wrong position.

Flexural Stiffness of Myosin Va Subdomains as Measured from Tethered Particle Motion

PubMed Central

Michalek, Arthur J.; Kennedy, Guy G.; Warshaw, David M.; Ali, M. Yusuf

2015-01-01

Myosin Va (MyoVa) is a processive molecular motor involved in intracellular cargo transport on the actin cytoskeleton. The motor's processivity and ability to navigate actin intersections are believed to be governed by the stiffness of various parts of the motor's structure. Specifically, changes in calcium may regulate motor processivity by altering the motor's lever arm stiffness and thus its interhead communication. In order to measure the flexural stiffness of MyoVa subdomains, we use tethered particle microscopy, which relates the Brownian motion of fluorescent quantum dots, which are attached to various single- and double-headed MyoVa constructs bound to actin in rigor, to the motor's flexural stiffness. Based on these measurements, the MyoVa lever arm and coiled-coil rod domain have comparable flexural stiffness (0.034 pN/nm). Upon addition of calcium, the lever arm stiffness is reduced 40% as a result of calmodulins potentially dissociating from the lever arm. In addition, the flexural stiffness of the full-length MyoVa construct is an order of magnitude less stiff than both a single lever arm and the coiled-coil rod. This suggests that the MyoVa lever arm-rod junction provides a flexible hinge that would allow the motor to maneuver cargo through the complex intracellular actin network. PMID:26770194

A Lever Coupling Mechanism in Dual-Mass Micro-Gyroscopes for Improving the Shock Resistance along the Driving Direction

PubMed Central

Gao, Yang; Li, Hongsheng; Huang, Libin; Sun, Hui

2017-01-01

This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope’s modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity. PMID:28468288

Abdominal muscle and epipubic bone function during locomotion in Australian possums: insights to basal mammalian conditions and Eutherian-like tendencies in Trichosurus.

PubMed

Reilly, Stephen M; McElroy, Eric J; White, Thomas D; Biknevicius, Audrone R; Bennett, Michael B

2010-04-01

Mammals have four hypaxial muscle layers that wrap around the abdomen between the pelvis, ribcage, and spine. However, the marsupials have epipubic bones extending anteriorly into the ventral hypaxial layers with two additional muscles extending to the ventral midline and femur. Comparisons of South American marsupials to basal eutherians have shown that all of the abdominal hypaxials are active bilaterally in resting ventilation. However, during locomotion marsupials employ an asymmetrical pattern of activity as the hypaxial muscles form a crosscouplet linkage that uses the epipubic bone as a lever to provide long-axis support of the body between diagonal limb couplets during each step. In basal eutherians, this system shifts off the femur and epipubic bones (which are lost) resulting in a shoulder to pelvis linkage associated with shifts in both the positions and activity patterns of the pectineus and rectus abdominis muscles during locomotion. In this study, we present data on hypaxial function in two species (Pseudocheirus peregrinus and Trichosurus vulpecula) representing the two major radiations of possums in Australia: the Pseudocheiridae (within the Petauroidea) and the Phalangeridae. Patterns of gait, motor activity, and morphology in these two Australian species were compared with previous work to examine the generality of 1) the crosscouplet lever system as the basal condition for the Marsupialia and 2) several traits hypothesized to be common to all mammals (hypaxial tonus during resting ventilation, ventilation to step synchrony during locomotion, and bilateral transversus abdominis activity during locomotor expiration). Our results validate the presence of the crosscouplet pattern and basic epipubic bone lever system in Australian possums and confirm the generality of basal mammalian patterns. However, several novelties discovered in Trichosurus, reveal that it exhibits an evolutionary transition to intermediate eutherian-like morphological and motor patterns paralleling many other unique features of this species. (c) 2009 Wiley-Liss, Inc.

A Long-Term BCI Study With ECoG Recordings in Freely Moving Rats.

PubMed

Costecalde, Thomas; Aksenova, Tetiana; Torres-Martinez, Napoleon; Eliseyev, Andriy; Mestais, Corinne; Moro, Cecile; Benabid, Alim Louis

2018-02-01

Brain Computer Interface (BCI) studies are performed in an increasing number of applications. Questions are raised about electrodes, data processing and effectors. Experiments are needed to solve these issues. To develop a simple BCI set-up to easier studies for improving the mathematical tools to process the ECoG to control an effector. We designed a simple BCI using transcranial electrodes (17 screws, three mechanically linked to create a common reference, 14 used as recording electrodes) to record Electro-Cortico-Graphic (ECoG) neuronal activities in rodents. The data processing is based on an online self-paced non-supervised (asynchronous) BCI paradigm. N-way partial least squares algorithm together with Continuous Wavelet Transformation of ECoG recordings detect signatures related to motor activities. Signature detection in freely moving rats may activate external effectors during a behavioral task, which involved pushing a lever to obtain a reward. After routine training, we showed that peak brain activity preceding a lever push (LP) to obtain food reward was located mostly in the cerebellar cortex with a higher correlation coefficient, suggesting a strong postural component and also in the occipital cerebral cortex. Analysis of brain activities provided a stable signature in the high gamma band (∼180Hz) occurring within 1500 msec before the lever push approximately around -400 msec to -500 msec. Detection of the signature from a single cerebellar cortical electrode triggers the effector with high efficiency (68% Offline and 30% Online) and rare false positives per minute in sessions about 30 minutes and up to one hour (∼2 online and offline). In summary, our results are original as compared to the rest of the literature, which involves rarely rodents, a simple BCI set-up has been developed in rats, the data show for the first time long-term, up to one year, unsupervised online control of an effector. © 2017 International Neuromodulation Society.

Engineering controllable bidirectional molecular motors based on myosin

PubMed Central

Chen, Lu; Nakamura, Muneaki; Schindler, Tony D.; Parker, David; Bryant, Zev

2012-01-01

Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells1, and have potential applications in molecular detection and diagnostic devices2,3. Engineering molecular motors with dynamically controllable properties will allow selective perturbation of mechanical processes in living cells, and yield optimized device components for complex tasks such as molecular sorting and directed assembly3. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions4,5 and other signals6. Here we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies7–11 and guided by a structural model12 for the redirected power stroke of myosin VI, we constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our general strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should enable spatiotemporal control over a range of motor properties including processivity, stride size13, and branchpoint turning14. PMID:22343382

Engineering controllable bidirectional molecular motors based on myosin

NASA Astrophysics Data System (ADS)

Chen, Lu; Nakamura, Muneaki; Schindler, Tony D.; Parker, David; Bryant, Zev

2012-04-01

Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells and have potential applications in molecular detection and diagnostic devices. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions and other signals. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies and guided by a structural model for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size and branchpoint turning.

Stirling engine power control and motion conversion mechanism

DOEpatents

Marks, David T.

1983-01-01

A motion conversion device for converting between the reciprocating motion of the pistons in a Stirling engine and the rotating motion of its output shaft, and for changing the stroke and phase of the pistons, includes a lever pivoted at one end and having a cam follower at the other end. The piston rod engages the lever intermediate its ends and the cam follower engages a cam keyed to the output shaft. The lever pivot can be moved to change the length of the moment arm defined between the cam follower and the piston rod the change the piston stroke and force exerted on the cam, and the levers can be moved in opposite directions to change the phase between pistons.

Effects Of Methylphenidate And Morphine On Delay-Discount Functions Obtained Within Sessions

PubMed Central

Pitts, Raymond C; McKinney, A. Patrick

2005-01-01

Four rats responded under a “self-control” procedure designed to obtain delay-discount functions within sessions. Each session consisted of seven blocks, with seven trials within each block. Each block consisted of two initial forced-choice trials followed by five free-choice trials. On choice trials, the rats could press either of two retractable levers. A press on one lever was followed by presentation of a smaller reinforcer (a single dipper presentation of a sucrose solution); a press on the other lever was followed by presentation of a larger reinforcer (four consecutive dipper presentations). The delay associated with the smaller reinforcer always was 0 s, whereas the signaled delay associated with the larger reinforcer increased across blocks (from 0 to 50 s). Under these conditions, the percentage of choices of the larger reinforcer decreased across blocks, and relatively reliable delay-discount functions were obtained within sessions. Doses of methylphenidate (1.0 to 17.0 mg/kg) and morphine (0.3 to 17.0 mg/kg) were then administered prior to selected sessions. Typically, intermediate doses of methylphenidate shifted the discount functions to the right (increased choices of the larger reinforcer). For 2 of the rats, this effect was pronounced; for the other 2 rats, this effect occurred after the range of delays for the larger reinforcer was decreased (0 to 20 s). On the other hand, in most cases morphine produced a slight leftward shift in the discount function (decreased choices of the larger reinforcer). The present procedure appears to be a useful and efficient method to characterize drug effects on an entire delay-discount function. As with many procedures used to study self-control choices, however, sources of control other than reinforcement delay and amount may have been operating in the present study, and these sources must be considered when interpreting drug effects. PMID:16047609

Alcohol operant self-administration: Investigating how alcohol-seeking behaviors predict drinking in mice using two operant approaches

PubMed Central

Blegen, Mariah B.; Silva, Daniel da Silva E; Bock, Roland; Morisot, Nadege; Ron, Dorit; Alvarez, Veronica A.

2018-01-01

Alcohol operant self-administration paradigms are critical tools for studying the neural circuits implicated in both alcohol-seeking and consummatory behaviors and for understanding the neural basis underlying alcohol-use disorders. In this study, we investigate the predictive value of two operant models of oral alcohol self-administration in mice, one in which alcohol is delivered into a cup following nose-poke responses with no accurate measurement of consumed alcohol solution, and another paradigm that provides access to alcohol via a sipper tube following lever presses and where lick rate and consumed alcohol volume can be measured. The goal was to identify a paradigm where operant behaviors such as lever presses and nose pokes, as well as other tracked behavior such as licks and head entries, can be used to reliably predict blood alcohol concentration (BAC). All mice were first exposed to alcohol in the home cage using the “drinking in the dark” (DID) procedure for 3 weeks and then were trained in alcohol self-administration using either of the operant paradigms for several weeks. Even without sucrose fading or food pre-training, mice acquired alcohol self-administration with both paradigms. However, neither lever press nor nose-poke rates were good predictors of alcohol intake or BAC. Only the lick rate and consumed alcohol were consistently and significantly correlated with BAC. Using this paradigm that accurately measures alcohol intake, unsupervised cluster analysis revealed three groups of mice: high-drinking (43%), low-drinking (37%), and non-drinking mice (20%). High-drinking mice showed faster acquisition of operant responding and achieved higher BACs than low-drinking mice. Lick rate and volume consumed varied with the alcohol concentration made available only for high- and low-drinking mice, but not for non-drinking mice. In addition, high- and low-drinking mice showed similar patterns during extinction and significant cue-induced reinstatement of seeking. Only high-drinking mice showed insensitivity to quinine adulteration, indicating a willingness to drink alcohol despite pairing with aversive stimuli. Thus, this study shows that relying on active presses is not an accurate determination of drinking behavior in mice. Only paradigms that allow for accurate measurements of consumed alcohol and/or lick rate are valid models of operant alcohol self-administration, where compulsive-like drinking could be accurately determined based on changes in alcohol intake when paired with bitter-tasting stimuli. PMID:29310048

Individual Differences in Dopamine Efflux in Nucleus Accumbens Shell and Core during Instrumental Learning

ERIC Educational Resources Information Center

Cheng, Jingjun; Feenstra, Matthijs G. P.

2006-01-01

Combined activation of dopamine D1- and NMDA-glutamate receptors in the nucleus accumbens has been strongly implicated in instrumental learning, the process in which an individual learns that a specific action has a wanted outcome. To assess dopaminergic activity, we presented rats with two sessions (30 trials each) of a one-lever appetitive…

An analysis of policy success and failure in formal evaluations of Australia's national mental health strategy (1992-2012).

PubMed

Grace, Francesca C; Meurk, Carla S; Head, Brian W; Hall, Wayne D; Harris, Meredith G; Whiteford, Harvey A

2017-05-30

Heightened fiscal constraints, increases in the chronic disease burden and in consumer expectations are among several factors contributing to the global interest in evidence-informed health policy. The present article builds on previous work that explored how the Australian Federal Government applied five instruments of policy, or policy levers, to implement a series of reforms under the Australian National Mental Health Strategy (NMHS). The present article draws on theoretical insights from political science to analyse the relative successes and failures of these levers, as portrayed in formal government evaluations of the NMHS. Documentary analysis of six evaluation documents corresponding to three National Mental Health Plans was undertaken. Both the content and approach of these government-funded, independently conducted evaluations were appraised. An overall improvement was apparent in the development and application of policy levers over time. However, this finding should be interpreted with caution due to variations in evaluation approach according to Plan and policy lever. Tabulated summaries of the success and failure of each policy initiative, ordered by lever type, are provided to establish a resource that could be consulted for future policy-making. This analysis highlights the complexities of health service reform and underscores the limitations of narrowly focused empirical approaches. A theoretical framework is provided that could inform the evaluation and targeted selection of appropriate policy levers in mental health.

The gearing function of running shoe longitudinal bending stiffness.

PubMed

Willwacher, Steffen; König, Manuel; Braunstein, Björn; Goldmann, Jan-Peter; Brüggemann, Gert-Peter

2014-07-01

The purpose of the present study was to investigate whether altered longitudinal bending stiffness (LBS) levels of the midsole of a running shoe lead to a systematic change in lower extremity joint lever arms of the ground reaction force (GRF). Joint moments and GRF lever arms in the sagittal plane were determined from 19 male subjects running at 3.5 m/s using inverse dynamics procedures. LBS was manipulated using carbon fiber insoles of 1.9 mm and 3.2 mm thickness. Increasing LBS led to a significant shift of joint lever arms to a more anterior position. Effects were more pronounced at distal joints. Ankle joint moments were not significantly increased in the presence of higher GRF lever arms when averaged over all subjects. Still, two individual strategies (1: increase ankle joint moments while keeping push-off times almost constant, 2: decrease ankle joint moments and increase push-off times) could be identified in response to increased ankle joint lever arms that might reflect individual differences between subjects with respect to strength capacities or anthropometric characteristics. The results of the present study indicate that LBS systematically influences GRF lever arms of lower extremity joints during the push-off phase in running. Further, individual responses to altered LBS levels could be identified that could aid in finding optimum LBS values for a given individual. Copyright © 2014 Elsevier B.V. All rights reserved.

Conductor load bearing roller for a gas-insulated transmission line having a corrugated outer conductor

DOEpatents

Fischer, William H.; Yoon, Kue H.

1984-04-10

A gas-insulated transmission line includes a corrugated outer conductor, an inner conductor disposed within and insulated from the outer conductor by means of support insulators and an insulating gas, and a transport device for supporting and permitting movement of the inner conductor/insulating support assembly axially along the corrugated outer conductor without radial displacement. The transport device includes two movable contacts, such as skids or rollers, supported on a common pivot lever, the pivot lever being rotatably disposed about a pivot lever axis, which pivot lever axis is in turn disposed on the periphery of a support insulator or particle trap if one is used. The movable contacts are separated axially a distance equal to the axial distance between the peaks and valleys of the corrugations of the outer conductor and separated radially a distance equal to the radial distance between the peaks and valleys of the corrugations of the outer conductor. The transport device has the pivot lever axis disposed perpendicular to the direction of travel of the inner conductor/insulating support assembly.

Increased sign-tracking behavior in adolescent rats.

PubMed

DeAngeli, Nicole E; Miller, Sarah B; Meyer, Heidi C; Bucci, David J

2017-11-01

An autoshaping procedure was used to test the notion that conditioned stimuli (CSs) gain greater incentive salience during adolescence than young adulthood under conditions of social isolation rearing and food restriction. Rats were single-housed and placed on food restriction during 10 daily training sessions in which a lever (CS + ) was presented then followed immediately by a food unconditioned stimulus (US). A second lever (CS - ) was presented on intermixed trials and was not reinforced. Despite the fact that food delivery was not contingent on the rats' behavior, all rats exhibited behaviors directed towards the lever (i.e., sign-tracking). In the adolescent group, the rate of lever pressing and the percentage of trials with a lever press were higher than in young adults. Initially, group differences were observed when rats were retrained when the adolescents had reached young adulthood. These findings support the hypothesis that cues that come to predict reward become imbued with excessive motivational value in adolescents, perhaps contributing to the hyper-responsiveness to reward-related stimuli typically observed during this period of development. © 2017 Wiley Periodicals, Inc.

Resurgence of Integrated Behavioral Units

PubMed Central

Bachá-Méndez, Gustavo; Reid, Alliston K; Mendoza-Soylovna, Adela

2007-01-01

Two experiments with rats examined the dynamics of well-learned response sequences when reinforcement contingencies were changed. Both experiments contained four phases, each of which reinforced a 2-response sequence of lever presses until responding was stable. The contingencies then were shifted to a new reinforced sequence until responding was again stable. Extinction-induced resurgence of previously reinforced, and then extinguished, heterogeneous response sequences was observed in all subjects in both experiments. These sequences were demonstrated to be integrated behavioral units, controlled by processes acting at the level of the entire sequence. Response-level processes were also simultaneously operative. Errors in sequence production were strongly influenced by the terminal, not the initial, response in the currently reinforced sequence, but not by the previously reinforced sequence. These studies demonstrate that sequence-level and response-level processes can operate simultaneously in integrated behavioral units. Resurgence and the development of integrated behavioral units may be dissociated; thus the observation of one does not necessarily imply the other. PMID:17345948

The dopamine D2/D3 receptor agonist quinpirole increases checking-like behaviour in an operant observing response task with uncertain reinforcement: A novel possible model of OCD?

PubMed Central

Eagle, Dawn M.; Noschang, Cristie; d’Angelo, Laure-Sophie Camilla; Noble, Christie A.; Day, Jacob O.; Dongelmans, Marie Louise; Theobald, David E.; Mar, Adam C.; Urcelay, Gonzalo P.; Morein-Zamir, Sharon; Robbins, Trevor W.

2014-01-01

Excessive checking is a common, debilitating symptom of obsessive-compulsive disorder (OCD). In an established rodent model of OCD checking behaviour, quinpirole (dopamine D2/3-receptor agonist) increased checking in open-field tests, indicating dopaminergic modulation of checking-like behaviours. We designed a novel operant paradigm for rats (observing response task (ORT)) to further examine cognitive processes underpinning checking behaviour and clarify how and why checking develops. We investigated i) how quinpirole increases checking, ii) dependence of these effects on D2/3 receptor function (following treatment with D2/3 receptor antagonist sulpiride) and iii) effects of reward uncertainty. In the ORT, rats pressed an ‘observing’ lever for information about the location of an ‘active’ lever that provided food reinforcement. High- and low-checkers (defined from baseline observing) received quinpirole (0.5 mg/kg, 10 treatments) or vehicle. Parametric task manipulations assessed observing/checking under increasing task demands relating to reinforcement uncertainty (variable response requirement and active-lever location switching). Treatment with sulpiride further probed the pharmacological basis of long-term behavioural changes. Quinpirole selectively increased checking, both functional observing lever presses (OLPs) and non-functional extra OLPs (EOLPs). The increase in OLPs and EOLPs was long-lasting, without further quinpirole administration. Quinpirole did not affect the immediate ability to use information from checking. Vehicle and quinpirole-treated rats (VEH and QNP respectively) were selectively sensitive to different forms of uncertainty. Sulpiride reduced non-functional EOLPs in QNP rats but had no effect on functional OLPs. These data have implications for treatment of compulsive checking in OCD, particularly for serotonin-reuptake-inhibitor treatment-refractory cases, where supplementation with dopamine receptor antagonists may be beneficial. PMID:24406720

Distinct Functional Modules for Discrete and Rhythmic Forelimb Movements in the Mouse Motor Cortex.

PubMed

Hira, Riichiro; Terada, Shin-Ichiro; Kondo, Masashi; Matsuzaki, Masanori

2015-09-30

Movements of animals are composed of two fundamental dynamics: discrete and rhythmic movements. Although the movements with distinct dynamics are thought to be differently processed in the CNS, it is unclear how they are represented in the cerebral cortex. Here, we investigated the cortical representation of movement dynamics by developing prolonged transcranial optogenetic stimulation (pTOS) using awake, channelrhodopsin-2 transgenic mice. We found two domains that induced discrete forelimb movements in the forward and backward directions, and these sandwiched a domain that generated rhythmic forelimb movements. The forward discrete movement had an intrinsic velocity profile and the rhythmic movement had an intrinsic oscillation frequency. Each of the forward discrete and rhythmic domains possessed intracortical synaptic connections within its own domain, independently projected to the spinal cord, and weakened the neuronal activity and movement induction of the other domain. pTOS-induced movements were also classified as ethologically relevant movements. Forepaw-to-mouth movement was mapped in a part of the forward discrete domain, while locomotion-like movement was in a part of the rhythmic domain. Interestingly, photostimulation of the rhythmic domain resulted in a nonrhythmic, continuous lever-pull movement when a lever was present. The motor cortex possesses functional modules for distinct movement dynamics, and these can adapt to environmental constraints for purposeful movements. Significance statement: Animal behavior has discrete and rhythmic components, such as reaching and locomotion. It is unclear how these movements with distinct dynamics are represented in the cerebral cortex. We investigated the dynamics of movements induced by long-duration transcranial photostimulation on the dorsal cortex of awake channelrhodopsin-2 transgenic mice. We found two domains causing forward and backward discrete forelimb movements and a domain for rhythmic forelimb movements. A domain for forward discrete movement and a domain for rhythmic movement mutually weakened neuronal activity and movement size. The photostimulation of the rhythmic domain also induced nonrhythmic, lever-pull movement, when the lever was present. Thus, the motor cortex has functional modules with distinct dynamics, and each module retains flexibility for adaptation to different environments. Copyright © 2015 the authors 0270-6474/15/3513311-12$15.00/0.

Regional heterogeneity for the intracranial self-administration of ethanol within the ventral tegmental area of female Wistar rats.

PubMed

Rodd-Henricks, Z A; McKinzie, D L; Crile, R S; Murphy, J M; McBride, W J

2000-04-01

Because current findings indicate that the selectively bred alcohol-preferring P line of rats self-administers 50-200 mg% ethanol (EtOH) directly into the ventral tegmental area (VTA), whereas the alcohol-nonpreferring NP line does not, it is important to determine whether unselected, common stock rats would self-administer EtOH directly into the VTA. In addition, because neuroanatomical and self-administration studies indicate that the VTA may be functionally heterogeneous, the present study was designed to determine whether there were subregional differences within the VTA for the intracranial self-administration (ICSA) of EtOH. The objective of this study was to employ the ICSA technique to determine whether adult female Wistar rats would self-administer EtOH directly into the VTA, and whether regional heterogeneity existed for EtOH self-infusion within the VTA. Following surgery to implant guide cannulae aimed at either the posterior or anterior VTA, subjects were placed in standard experimental chambers equipped with an 'active lever' [fixed ratio (FR)1 schedule of reinforcement], which caused the delivery of the infusate, and an 'inactive lever', which had no programmed consequence. Subjects were assigned to groups that self-administered either artificial cerebrospinal fluid (aCSF) throughout, or 100-400 mg% EtOH for the first four sessions (acquisition), aCSF in sessions 5 and 6 (extinction), and EtOH again during session 7 (reinstatement). During the four acquisition sessions, rats with posterior VTA placements readily self-administered 200 mg% and 250 mg% EtOH and discriminated between the active and inactive levers. These subjects also demonstrated extinction, when aCSF was substituted for EtOH, and reinstatement when EtOH was reintroduced. Rats with posterior VTA placements self-infused 300 mg% and 400 mg% EtOH, and demonstrated lever discrimination only during the initial acquisition sessions. In contrast, rats with anterior VTA placements did not self-administer EtOH. The findings suggest that EtOH is reinforcing within the posterior VTA of Wistar rats, and the VTA is a functionally heterogeneous structure with regard to EtOH reinforcement.

In Vivo Orientation of Single Myosin Lever Arms in Zebrafish Skeletal Muscle

PubMed Central

Sun, Xiaojing; Ekker, Stephen C.; Shelden, Eric A.; Takubo, Naoko; Wang, Yihua; Burghardt, Thomas P.

2014-01-01

Cardiac and skeletal myosin assembled in the muscle lattice power contraction by transducing ATP free energy into the mechanical work of moving actin. Myosin catalytic/lever-arm domains comprise the transduction/mechanical coupling machinery that move actin by lever-arm rotation. In vivo, myosin is crowded and constrained by the fiber lattice as side chains are mutated and otherwise modified under normal, diseased, or aging conditions that collectively define the native myosin environment. Single-myosin detection uniquely defines bottom-up characterization of myosin functionality. The marriage of in vivo and single-myosin detection to study zebrafish embryo models of human muscle disease is a multiscaled technology that allows one-to-one registration of a selected myosin molecular alteration with muscle filament-sarcomere-cell-fiber-tissue-organ- and organism level phenotypes. In vivo single-myosin lever-arm orientation was observed at superresolution using a photoactivatable-green-fluorescent-protein (PAGFP)-tagged myosin light chain expressed in zebrafish skeletal muscle. By simultaneous observation of multiphoton excitation fluorescence emission and second harmonic generation from myosin, we demonstrated tag specificity for the lever arm. Single-molecule detection used highly inclined parallel beam illumination and was verified by quantized photoactivation and photobleaching. Single-molecule emission patterns from relaxed muscle in vivo provided extensive superresolved dipole orientation constraints that were modeled using docking scenarios generated for the myosin (S1) and GFP crystal structures. The dipole orientation data provided sufficient constraints to estimate S1/GFP coordination. The S1/GFP coordination in vivo is rigid and the lever-arm orientation distribution is well-ordered in relaxed muscle. For comparison, single myosins in relaxed permeabilized porcine papillary muscle fibers indicated slightly differently oriented lever arms and rigid S1/GFP coordination. Lever arms in both muscles indicated one preferred spherical polar orientation and widely distributed azimuthal orientations relative to the fiber symmetry axis. Cardiac myosin is more radially displaced from the fiber axis. Probe rigidity implies the PAGFP tag reliably indicates cross-bridge orientation in situ and in vivo. PMID:25229148

Corticospinal signals recorded with MEAs can predict the volitional forearm forces in rats.

PubMed

Guo, Yi; Mesut, Sahin; Foulds, Richard A; Adamovich, Sergei V

2013-01-01

We set out to investigate if volitional components in the descending tracts of the spinal cord white matter can be accessed with multi-electrode array (MEA) recording technique. Rats were trained to press a lever connected to a haptic device with force feedback to receive sugar pellets. A flexible-substrate multi-electrode array was chronically implanted into the dorsal column of the cervical spinal cord. Field potentials and multi-unit activities were recorded from the descending axons of the corticospinal tract while the rat performed a lever pressing task. Forelimb forces, recorded with the sensor attached to the lever, were reconstructed using the hand position data and the neural signals through multiple trials over three weeks. The regression coefficients found from the trial set were cross-validated on the other trials recorded on same day. Approximately 30 trials of at least 2 seconds were required for accurate model estimation. The maximum correlation coefficient between the actual and predicted force was 0.7 in the test set. Positional information and its interaction with neural signals improved the correlation coefficient by 0.1 to 0.15. These results suggest that the volitional information contained in the corticospinal tract can be extracted with multi-channel neural recordings made with parenchymal electrodes.

Policy for material efficiency--sustainable taxation as a departure from the throwaway society.

PubMed

Stahel, Walter R

2013-03-13

The present economy is not sustainable with regard to its per capita material consumption. A dematerialization of the economy of industrialized countries can be achieved by a change in course, from an industrial economy built on throughput to a circular economy built on stock optimization, decoupling wealth and welfare from resource consumption while creating more work. The business models of a circular economy have been known since the mid-1970s and are now applied in a number of industrial sectors. This paper argues that a simple and convincing lever could accelerate the shift to a circular economy, and that this lever is the shift to a tax system based on the principles of sustainability: not taxing renewable resources including human labour--work--but taxing non-renewable resources instead is a powerful lever. Taxing materials and energies will promote low-carbon and low-resource solutions and a move towards a 'circular' regional economy as opposed to the 'linear' global economy requiring fuel-based transport for goods throughput. In addition to substantial improvements in material and energy efficiency, regional job creation and national greenhouse gas emission reductions, such a change will foster all activities based on 'caring', such as maintaining cultural heritage and natural wealth, health services, knowledge and know-how.

The Effect of Varying Biting Position on Relative Jaw Muscle EMG activity

DTIC Science & Technology

1988-09-01

with muscle force is the key to 13 this approach as it allows inference of muscle contraction activity from EMG data. This relationship has been the...5! 15 LITERATURE REVIEW Introduction: The study of the physiology of bite force, muscle contraction force, joint reaction force and the lever system...Currently, the best method of indirectly observing muscle contraction activity is through electromyography. Although there appears to be a time delay

Differential effects of serotonin-specific and excitotoxic lesions of OFC on conditioned reinforcer devaluation and extinction in rats

PubMed Central

West, Elizabeth A.; Forcelli, Patrick A.; McCue, David L.; Malkova, Ludise

2013-01-01

The orbitofrontal cortex (OFC) is critical for behavioral adaptation in response to changes in reward value. Here we investigated, in rats, the role of OFC and, specifically, serotonergic neurotransmission within OFC in a reinforcer devaluation task (which measures behavioral flexibility). This task used two visual cues, each predicting one of two foods, with the spatial position (left-right) of the cues above two levers pseudorandomized across trials. An instrumental action (lever press) was required for reinforcer delivery. After training, rats received either excitotoxic OFC lesions made by NMDA (N-methyl-D-aspartic acid), serotonin-specific OFC lesions made by 5,7-DHT (5,7-dihydroxytryptamine), or sham lesions. In sham-lesioned rats, devaluation of one food (by feeding to satiety) significantly decreased responding to the cue associated with that food, when both cues were presented simultaneously during extinction. Both types of OFC lesions disrupted the devaluation effect. In contrast, extinction learning was not affected by serotonin-specific lesions and was only mildly retarded in rats with excitotoxic lesions. Thus, serotonin within OFC is necessary for appropriately adjusting behavior towards cues that predict reward but not for reducing responses in the absence of reward. Our results are the first to demonstrate that serotonin in OFC is necessary for reinforcer devaluation, but not extinction. PMID:23458741

A secure transmission scheme of streaming media based on the encrypted control message

NASA Astrophysics Data System (ADS)

Li, Bing; Jin, Zhigang; Shu, Yantai; Yu, Li

2007-09-01

As the use of streaming media applications increased dramatically in recent years, streaming media security becomes an important presumption, protecting the privacy. This paper proposes a new encryption scheme in view of characteristics of streaming media and the disadvantage of the living method: encrypt the control message in the streaming media with the high security lever and permute and confuse the data which is non control message according to the corresponding control message. Here the so-called control message refers to the key data of the streaming media, including the streaming media header and the header of the video frame, and the seed key. We encrypt the control message using the public key encryption algorithm which can provide high security lever, such as RSA. At the same time we make use of the seed key to generate key stream, from which the permutation list P responding to GOP (group of picture) is derived. The plain text of the non-control message XORs the key stream and gets the middle cipher text. And then obtained one is permutated according to P. In contrast the decryption process is the inverse process of the above. We have set up a testbed for the above scheme and found our scheme is six to eight times faster than the conventional method. It can be applied not only between PCs but also between handheld devices.

Free-Operant Avoidance Behavior by Rats after Reinforcer Revaluation Using Opioid Agonists and d-Amphetamine

PubMed Central

Urcelay, Gonzalo; Mar, Adam; Dickinson, Anthony; Robbins, Trevor

2014-01-01

The associative processes that support free-operant instrumental avoidance behavior are still unknown. We used a revaluation procedure to determine whether the performance of an avoidance response is sensitive to the current value of the aversive, negative reinforcer. Rats were trained on an unsignaled, free-operant lever press avoidance paradigm in which each response avoided or escaped shock and produced a 5 s feedback stimulus. The revaluation procedure consisted of noncontingent presentations of the shock in the absence of the lever either paired or unpaired with systemic morphine and in a different cohort with systemic d-amphetamine. Rats were then tested drug free during an extinction test. In both the d-amphetamine and morphine groups, pairing of the drug and shock decreased subsequent avoidance responding during the extinction test, suggesting that avoidance behavior was sensitive to the current incentive value of the aversive negative reinforcer. Experiment 2 used central infusions of D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), a mu-opioid receptor agonist, in the periacqueductal gray and nucleus accumbens shell to revalue the shock. Infusions of DAMGO in both regions replicated the effects seen with systemic morphine. These results are the first to demonstrate the impact of revaluation of an aversive reinforcer on avoidance behavior using pharmacological agents, thereby providing potential therapeutic targets for the treatment of avoidance behavior symptomatic of anxiety disorders. PMID:24790199

The reinforcing property and the rewarding aftereffect of wheel running in rats: a combination of two paradigms.

PubMed

Belke, Terry W; Wagner, Jason P

2005-02-28

Wheel running reinforces the behavior that generates it and produces a preference for the context that follows it. The goal of the present study was to demonstrate both of these effects in the same animals. Twelve male Wistar rats were first exposed to a fixed-interval 30 s schedule of wheel-running reinforcement. The operant was lever-pressing and the reinforcer was the opportunity to run for 45 s. Following this phase, the method of place conditioning was used to test for a rewarding aftereffect following operant sessions. On alternating days, half the rats responded for wheel-running reinforcement while the other half remained in their home cage. Upon completion of the wheel-running reinforcement sessions, rats that ran and rats that remained in their home cages were placed into a chamber of a conditioned place preference (CPP) apparatus for 30 min. Each animal received six pairings of a distinctive context with wheel running and six pairings of a different context with their home cage. On the test day, animals were free to move between the chambers for 10 min. Results showed a conditioned place preference for the context associated with wheel running; however, time spent in the context associated with running was not related to wheel-running rate, lever-pressing rate, or post-reinforcement pause duration. (c) 2004 Elsevier B.V. All rights reserved.

Differential effects of serotonin-specific and excitotoxic lesions of OFC on conditioned reinforcer devaluation and extinction in rats.

PubMed

West, Elizabeth A; Forcelli, Patrick A; McCue, David L; Malkova, Ludise

2013-06-01

The orbitofrontal cortex (OFC) is critical for behavioral adaptation in response to changes in reward value. Here we investigated, in rats, the role of OFC and, specifically, serotonergic neurotransmission within OFC in a reinforcer devaluation task (which measures behavioral flexibility). This task used two visual cues, each predicting one of two foods, with the spatial position (left-right) of the cues above two levers pseudorandomized across trials. An instrumental action (lever press) was required for reinforcer delivery. After training, rats received either excitotoxic OFC lesions made by NMDA (N-methyl-d-aspartic acid), serotonin-specific OFC lesions made by 5,7-DHT (5,7-dihydroxytryptamine), or sham lesions. In sham-lesioned rats, devaluation of one food (by feeding to satiety) significantly decreased responding to the cue associated with that food, when both cues were presented simultaneously during extinction. Both types of OFC lesions disrupted the devaluation effect. In contrast, extinction learning was not affected by serotonin-specific lesions and was only mildly retarded in rats with excitotoxic lesions. Thus, serotonin within OFC is necessary for appropriately adjusting behavior toward cues that predict reward but not for reducing responses in the absence of reward. Our results are the first to demonstrate that serotonin in OFC is necessary for reinforcer devaluation, but not extinction. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of D-cycloserine on the extinction of appetitive operant learning

PubMed Central

Vurbic, Drina; Gold, Benjamin; Bouton, Mark E.

2011-01-01

Four experiments with rat subjects examined whether D-cycloserine (DCS), a partial NMDA agonist, facilitates the extinction of operant lever-pressing reinforced by food. Previous research has demonstrated that DCS facilitates extinction learning with methods that involve Pavlovian extinction. In the current experiments, operant conditioning occurred in Context A, extinction in Context B, and then testing occurred in both the extinction and conditioning contexts. Experiments 1a and 1b tested the effects of three doses of DCS (5, 15, and 30 mg/kg) on the extinction of lever pressing trained as a free operant. Experiment 2 examined their effects when extinction of the free operant was conducted in the presence of non-response-contingent deliveries of the reinforcer (which theoretically reduced the role of generalization decrement in suppressing responding). Experiment 3 examined their effects on extinction of a discriminated operant, i.e., one that had been reinforced in the presence of a discriminative stimulus, but not in its absence. A strong ABA renewal effect was observed in all four experiments during testing. However, despite the use of DCS doses and a drug administration procedure that facilitates the extinction of Pavlovian learning, there was no evidence in any experiment that DCS facilitated operant extinction learning assessed in either the extinction or the conditioning context. DCS may primarily facilitate learning processes that underlie Pavlovian, rather than purely operant, extinction. PMID:21688894

29 CFR 1918.53 - Cargo winches.

Code of Federal Regulations, 2010 CFR

2010-07-01

... control levers operate with excessive friction or excessive play. (c) Double gear winches or other winches... left unattended, control levers shall be placed in the neutral position and the power shall be shut off...

Single-Lever Power Control for General Aviation Aircraft Promises Improved Efficiency and Simplified Pilot Controls

NASA Technical Reports Server (NTRS)

Musgrave, Jeffrey L.

1997-01-01

General aviation research is leading to major advances in internal combustion engine control systems for single-engine, single-pilot aircraft. These advances promise to increase engine performance and fuel efficiency while substantially reducing pilot workload and increasing flight safety. One such advance is a single-lever power control (SLPC) system, a welcome departure from older, less user-friendly, multilever engine control systems. The benefits of using single-lever power controls for general aviation aircraft are improved flight safety through advanced engine diagnostics, simplified powerplant operations, increased time between overhauls, and cost-effective technology (extends fuel burn and reduces overhaul costs). The single-lever concept has proven to be so effective in preliminary studies that general aviation manufacturers are making plans to retrofit current aircraft with the technology and are incorporating it in designs for future aircraft.

Effects of orbitofrontal cortex lesions on autoshaped lever pressing and reversal learning.

PubMed

Chang, Stephen E

2014-10-15

A cue associated with a rewarding event can trigger behavior towards the cue itself due to the cue acquiring incentive value through its pairing with the rewarding outcome (i.e., sign-tracking). For example, rats will approach, press, and attempt to "consume" a retractable lever conditioned stimulus (CS) that signals delivery of a food unconditioned stimulus (US). Attending to food-predictive CSs is important when seeking out food, and it is just as important to be able to modify one's behavior when the relationships between CSs and USs are changed. Using a discriminative autoshaping procedure with lever CSs, the present study investigated the effects of orbitofrontal cortex (OFC) lesions on sign-tracking and reversal learning. Insertion of one lever was followed by sucrose delivery upon retraction, and insertion of another lever was followed by nothing. After the acquisition phase, the contingencies between the levers and outcomes were reversed. Bilateral OFC lesions had no effect on the acquisition of sign-tracking. However, OFC-lesioned rats showed substantial deficits in acquiring sign-tracking compared to sham-lesioned rats once the stimulus-outcome contingencies were reversed. Over the course of reversal learning, OFC-lesioned rats were able to reach comparable levels of sign-tracking as sham-lesioned rats. These findings suggest that OFC is not necessary for the ability of a CS to acquire incentive value and provide more evidence that OFC is critical for modifying behavior appropriately following a change in stimulus-outcome contingencies. Copyright © 2014 Elsevier B.V. All rights reserved.

Parallel Professionalism in an Era of Standardisation

ERIC Educational Resources Information Center

Stone-Johnson, Corrie

2014-01-01

Today's American educational context is characterised by increasing standardisation coupled with heightened accountability. While some view standardisation as a lever for equity, many view it as problematic for the work of teachers. Efforts to improve student achievement by focusing on the activities of teachers have resulted in an over-riding…

75 FR 37375 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

..., and Teaching Policy Act of 1977, as amended (7 U.S.C. 3101); the Smith-Lever Act; and other... system for ongoing research and education activities in agriculture, food science, human nutrition, and..., or failure to collect this information, would severely compromise one of NIFA' primary functions...

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

PubMed Central

Levy, AnneMarie; Limebeer, Cheryl L.; Ferdinand, Justin; Shillingford, Ucal; Parker, Linda A.; Leri, Francesco

2014-01-01

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e. 8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e. one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets. PMID:24561923

Non-binding conductor load bearing roller for a gas-insulated transmission line having a corrugated outer conductor

DOEpatents

Fischer, William H.

1984-01-01

A gas-insulated transmission line includes a corrugated outer conductor, an inner conductor disposed within and insulated from the outer conductor by means of support insulators and an insulating gas, and a non-binding transport device for supporting and permitting movement of the inner conductor/insulating support assembly axially along the corrugated outer conductor without radial displacement and for moving without binding along corrugations of any slope less than vertical. The transport device includes two movable contacts, such as skids or rollers, supported on a common pivot lever, the pivot lever being rotatably disposed about a pivot lever axis, which pivot lever axis is in turn disposed on the periphery of a support insulator or particle trap if one is used. The movable contacts are separated axially a distance equal to the axial distance between the peaks and valleys of the corrugations of the outer conductor and separated radially a distance equal to the radial distance between the peaks and valleys of the corrugations of the outer conductor. The transport device has the pivot lever axis disposed parallel to the motion of travel of the inner conductor/insulating support assembly.

A compensation method of lever arm effect for tri-axis hybrid inertial navigation system based on fiber optic gyro

NASA Astrophysics Data System (ADS)

Liu, Zengjun; Wang, Lei; Li, Kui; Gao, Jiaxin

2017-05-01

Hybrid inertial navigation system (HINS) is a new kind of inertial navigation system (INS), which combines advantages of platform INS, strap-down INS and rotational INS. HINS has a physical platform to isolate the angular motion as platform INS does, HINS also uses strap-down attitude algorithms and applies rotation modulation technique. Tri-axis HINS has three gimbals to isolate the angular motion in the dynamic base, in which way the system can reduce the effects of angular motion and improve the positioning precision. However, the angular motion will affect the compensation of some error parameters, especially for the lever arm effect. The lever arm effect caused by position errors between the accelerometers and rotation center cannot be ignored due to the rapid rotation of inertial measurement unit (IMU) and it will cause fluctuation and stage in velocity in HINS. The influences of angular motion on the lever arm effect compensation are analyzed firstly in this paper, and then the compensation method of lever arm effect based on the photoelectric encoders in dynamic base is proposed. Results of experiments on turntable show that after compensation, the fluctuations and stages in velocity curve disappear.

35. END VIEW, INTERIOR, SHOWING SWITCHING LEVERS, BERK SWITCH TOWER, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

35. END VIEW, INTERIOR, SHOWING SWITCHING LEVERS, BERK SWITCH TOWER, SOUTH NORWALK - New York, New Haven & Hartford Railroad, Automatic Signalization System, Long Island Sound shoreline between Stamford & New Haven, Stamford, Fairfield County, CT

Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task

PubMed Central

Miller, Rikki L.A.

2017-01-01

Abstract The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior. PMID:29034318

Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task.

PubMed

Miller, Rikki L A; Francoeur, Miranda J; Gibson, Brett M; Mair, Robert G

2017-01-01

The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine.

PubMed

Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M

2017-07-01

In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine

PubMed Central

Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M.

2016-01-01

In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats’ response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6-h/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week, or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25, and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. PMID:26989042

Extinction of Chained Instrumental Behaviors: Effects of Procurement Extinction on Consumption Responding

PubMed Central

Thrailkill, Eric A.; Bouton, Mark E.

2015-01-01

Instrumental behavior often consists of sequences or chains of responses that minimally include procurement behaviors that enable subsequent consumption behaviors. In such chains, behavioral units are linked by access to one another and eventually to a primary reinforcer, such as food or a drug. The present experiments examined the effects of extinguishing procurement responding on consumption responding after training of a discriminated heterogeneous instrumental chain. Rats learned to make a procurement response (e.g., pressing a lever) in the presence of a distinctive discriminative stimulus; making that response led to the presentation of a second discriminative stimulus that set the occasion for a consumption response (e.g., pulling a chain), which then produced a food-pellet reinforcer. Experiment 1 showed that extinction of either the full procurement-consumption chain or procurement alone weakened the consumption response tested in isolation. Experiment 2 replicated the procurement extinction effect and further demonstrated that the opportunity to make the procurement response, as opposed to simple exposure to the procurement stimulus alone, was required. In Experiment 3, rats learned 2 distinct discriminated heterogeneous chains; extinction of 1 procurement response specifically weakened the consumption response that had been associated with it. The results suggest that learning to inhibit the procurement response may produce extinction of consumption responding through mediated extinction. The experiments suggest the importance of an associative analysis of instrumental behavior chains. PMID:25915751

Concurrent progressive ratio schedules: Effects of reinforcer probability on breakpoint and response allocation.

PubMed

Jarmolowicz, David P; Sofis, Michael J; Darden, Alexandria C

2016-07-01

Although progressive ratio (PR) schedules have been used to explore effects of a range of reinforcer parameters (e.g., magnitude, delay), effects of reinforcer probability remain underexplored. The present project used independently progressing concurrent PR PR schedules to examine effects of reinforcer probability on PR breakpoint (highest completed ratio prior to a session terminating 300s pause) and response allocation. The probability of reinforcement on one lever remained at 100% across all conditions while the probability of reinforcement on the other lever was systematically manipulated (i.e., 100%, 50%, 25%, 12.5%, and a replication of 25%). Breakpoints systematically decreased with decreasing reinforcer probabilities while breakpoints on the control lever remained unchanged. Patterns of switching between the two levers were well described by a choice-by-choice unit price model that accounted for the hyperbolic discounting of the value of probabilistic reinforcers. Copyright © 2016 Elsevier B.V. All rights reserved.

Beta-adrenoreceptor blockade abolishes atomoxetine-induced risk taking.

PubMed

Yang, Fan Nils; Pan, Jing Samantha; Li, Xinwang

2016-01-01

Clinical studies have shown that patients with exaggerated risk-taking tendencies have high baseline levels of norepinephrine. In this work, we systemically manipulated norepinephrine levels in rats and studied their behavioral changes in a probabilistic discounting task, which is a paradigm for gauging risk taking. This study aims to explore the effects of the selective norepinephrine reuptake inhibitor (atomoxetine at doses of 0.6, 1.0 and 1.8 mg/kg), and receptor selective antagonists (propranolol at a single dose of 1.0/kg, and prazosin at a single dose of 0.1 mg/kg), on risk taking using a probabilistic discounting task. In this task, there were two levers available to rats: pressing the 'small/certain' lever guaranteed a single food pellet, and pressing the 'large/risky' lever yielded either four pellets or none. The probability of receiving four food pellets decreased across the four experimental blocks from 100% to 12.5%. Atomoxetine increased the tendency to choose the large/risky lever. It significantly reduced the lose-shift effect (i.e. pressing a different lever after losing a trial), but did not affect the win-stay effect (i.e. pressing the same lever after winning a trial). Furthermore, co-administration of beta-adrenoreceptor antagonist, propranolol, eliminated the effects of atomoxetine on risk taking and the lose-shift effect; but co-administration of alpha1-adrenoreceptor antagonist, prazosin, did not. Atomoxetine boosted NE levels and increased risk taking. This was because atomoxetine decreased rats' sensitivity to losses. These effects were likely mediated by beta-adrenoreceptor. Copyright © 2015 Elsevier Inc. All rights reserved.

7 CFR 3419.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 1444 of NARETPA or under sections 3(b) and (c) of the Smith-Lever Act, 7 U.S.C. 343(b) and (c... cooperative extension under sections 1444 and 1445 of NARETPA, the Hatch Act of 1887, and the Smith-Lever Act...

Learn about Physical Science: Simple Machines. [CD-ROM].

ERIC Educational Resources Information Center

2000

This CD-ROM, designed for students in grades K-2, explores the world of simple machines. It allows students to delve into the mechanical world and learn the ways in which simple machines make work easier. Animated demonstrations are provided of the lever, pulley, wheel, screw, wedge, and inclined plane. Activities include practical matching and…

46 CFR 163.002-21 - Approval tests.

Code of Federal Regulations, 2011 CFR

2011-10-01

... must not break or crack during these tests. (2) Platform strength. If the pilot hoist has a lift... deck interlock must prevent movement of the ladder or lift platform when the lever is activated. (4... of the hoist is placed on its ladder or lift platform. The ladder or lift platform is repeatedly...

Public Libraries: A Vital Space for Family Engagement

ERIC Educational Resources Information Center

Lopez, M. Elena; Caspe, Margaret; McWilliams, Lorette

2016-01-01

Children and youth learn in countless ways, anywhere, anytime. And one of the most powerful levers of children's learning--from the early childhood years through adolescence--is families. For families, libraries provide the books, media, and activities that help them open doors for children's literacy and lifelong learning. Libraries are poised to…

Simple Machine Junk Cars

ERIC Educational Resources Information Center

Herald, Christine

2010-01-01

During the month of May, the author's eighth-grade physical science students study the six simple machines through hands-on activities, reading assignments, videos, and notes. At the end of the month, they can easily identify the six types of simple machine: inclined plane, wheel and axle, pulley, screw, wedge, and lever. To conclude this unit,…

Method and system for dual resolution translation stage

DOEpatents

Halpin, John Michael

2014-04-22

A dual resolution translation stage includes a stage assembly operable to receive an optical element and a low resolution adjustment device mechanically coupled to the stage assembly. The dual resolution stage also includes an adjustable pivot block mechanically coupled to the stage assembly. The adjustable pivot block includes a pivot shaft. The dual resolution stage further includes a lever arm mechanically coupled to the adjustable pivot block. The lever arm is operable to pivot about the pivot shaft. The dual resolution stage additionally includes a high resolution adjustment device mechanically coupled to the lever arm and the stage assembly.

Drum ring removal/installation tool

DOEpatents

Andrade, William Andrew [Livermore, CA

2006-11-14

A handheld tool, or a pair of such tools, such as for use in removing/installing a bolt-type clamping ring on a container barrel/drum, where the clamping ring has a pair of clamping ends each with a throughbore. Each tool has an elongated handle and an elongated lever arm transversely connected to one end of the handle. The lever arm is capable of being inserted into the throughbore of a selected clamping end and leveraged with the handle to exert a first moment on the selected clamping end. Each tool also has a second lever arm, such as a socket with an open-ended slot, which is suspended alongside the first lever arm. The second lever arm is capable of engaging the selected clamping end and being leveraged with the handle to exert a second moment which is orthogonal to the first moment. In this manner, the first and second moments operate to hold the selected clamping end fixed relative to the tool so that the selected clamping end may be controlled with the handle. The pair of clamping ends may also be simultaneously and independently controlled with the use of two handles/tools so as to contort the geometry of the drum clamping ring and enable its removal/installation.

A review of manual wheelchairs.

PubMed

Flemmer, Claire L; Flemmer, Rory C

2016-01-01

To review the scientific literature published in the last 14 years on the different types of manual wheelchairs. A systematic review of the literature was conducted to find the recent research on manual wheelchairs. The findings of 77 references on pushrim-propelled wheelchairs, crank-propelled wheelchairs, lever-propelled wheelchairs, geared manual wheelchairs and pushrim-activated power-assist wheelchairs are reported. The pushrim-propelled wheelchair is light, easy to steer and has good indoor manoeuvrability but is very inefficient and causes serious upper body overloading so that long-term use leads to steadily deteriorating capability for the user and ultimately a transition to a powered chair. Whilst the latter is less physically demanding, the sedentary lifestyle and decreasing muscle use lead to several secondary health problems. Crank- and lever-propelled wheelchairs and geared pushrim wheelchairs are more efficient and less demanding and may improve the quality of life of the user by expanding the range of accessible environments, reducing upper body pain, increasing independence and avoiding or delaying the 'debilitating cycle'. However, wheelchairs with these alternative modes of propulsion are often heavier, wider and/or longer and are less easy to steer, brake and fold than the pushrim wheelchair. Implications for rehabilitation Pushrim-propelled wheelchairs are difficult to drive on outdoor paths (grass and gravel/sand surfaces) and ramps so that users are confined to restricted environments and have limited participation in everyday activities. The repetitive strain imposed on the upper body by pushrim propulsion leads to very high prevalence of shoulder and wrist pain in manual wheelchair users. Crank-propelled and lever-propelled wheelchairs are more efficient and less straining than pushrim propelled wheelchairs, allowing users to access more challenging environments, prolong independence and improve the quality of life.

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

PubMed Central

Font, Laura; Mingote, Susana; Farrar, Andrew M.; Pereira, Mariana; Worden, Lila; Stopper, Colin; Port, Russell G.

2009-01-01

Rationale Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related processes, emerging evidence also implicates adenosine A2A receptors. Objective The present work was undertaken to test the hypothesis that accumbens A2A receptor stimulation would produce effects similar to those produced by DA depletion or antagonism. Materials and methods Three experiments assessed the effects of the adenosine A2A agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions. Results Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A2A receptor agonist CGS 21680 (6.0–24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective. Conclusions Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A2A receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A2A receptors appear to be a component of the brain circuitry regulating effort-related choice behavior. PMID:18491078

The effects of the novel DA D3 receptor antagonist SR 21502 on cocaine reward, cocaine seeking and cocaine-induced locomotor activity in rats.

PubMed

Galaj, E; Ananthan, S; Saliba, M; Ranaldi, Robert

2014-02-01

There is a focus on developing D3 receptor antagonists as cocaine addiction treatments. We investigated the effects of a novel selective D3 receptor antagonist, SR 21502, on cocaine reward, cocaine-seeking, food reward, spontaneous locomotor activity and cocaine-induced locomotor activity in rats. In Experiment 1, rats were trained to self-administer cocaine under a progressive ratio (PR) schedule of reinforcement and tested with vehicle or one of three doses of SR 21502. In Experiment 2, animals were trained to self-administer cocaine under a fixed ratio schedule of reinforcement followed by extinction of the response. Then, animals were tested with vehicle or one of the SR 21502 doses on cue-induced reinstatement of responding. In Experiment 3, animals were trained to lever press for food under a PR schedule and tested with vehicle or one dose of the compound. In Experiments 4 and 5, in separate groups of animals, the vehicle and three doses of SR 21502 were tested on spontaneous or cocaine (10 mg/kg, IP)-induced locomotor activity, respectively. SR 21502 produced significant, dose-related (3.75, 7.5 and 15 mg/kg) reductions in breakpoint for cocaine self-administration, cue-induced reinstatement (3.75, 7.5 and 15 mg/kg) and cocaine-induced locomotor activity (3.75, 7.5 and 15 mg/kg) but failed to reduce food self-administration and spontaneous locomotor activity. SR 21502 decreases cocaine reward, cocaine-seeking and locomotor activity at doses that have no effect on food reward or spontaneous locomotor activity. These data suggest SR 21502 may selectively inhibit cocaine's rewarding, incentive motivational and stimulant effects.

The endomembrane sheath: a key structure for understanding the plant cell?

NASA Technical Reports Server (NTRS)

Reuzeau, C.; McNally, J. G.; Pickard, B. G.

1997-01-01

Recent evidence suggests that integrin is abundant in endomembranes of plant cells, and the endomembranes are clad by a sheath of cytoskeleton including F-actin. A role for endomembrane integrin and the endomembrane sheath is proposed: this system might orchestrate metabolic regulation by providing and modulating loci for channelling, and might accelerate channeling as needed by dragging the endoplasmic reticulum (ER) and organelles through the cytoplasm. To accomplish this "streaming", F-actin might lever against the rest of the endomembrane sheath and the ER might also lever against adhesion sites (i.e., plasmodesmata and plasmalemmal control centers). As an important agent in the control of cellular activities, according to this model, the endomembrane sheath would play a major part in responses to diverse signals and stresses, and under extreme stress cell survival would depend on the ability of the system to maintain enough integrity to direct critical syntheses and degradations.

Study of Lever-Arm Effect Using Embedded Photogrammetry and On-Board GPS Receiver on Uav for Metrological Mapping Purpose and Proposal of a Free Ground Measurements Calibration Procedure

NASA Astrophysics Data System (ADS)

Daakir, M.; Pierrot-Deseilligny, M.; Bosser, P.; Pichard, F.; Thom, C.; Rabot, Y.

2016-03-01

Nowadays, Unmanned Aerial Vehicle (UAV) on-board photogrammetry knows a significant growth due to the democratization of using drones in the civilian sector. Also, due to changes in regulations laws governing the rules of inclusion of a UAV in the airspace which become suitable for the development of professional activities. Fields of application of photogrammetry are diverse, for instance: architecture, geology, archaeology, mapping, industrial metrology, etc. Our research concerns the latter area. Vinci-Construction- Terrassement is a private company specialized in public earthworks that uses UAVs for metrology applications. This article deals with maximum accuracy one can achieve with a coupled camera and GPS receiver system for direct-georeferencing of Digital Surface Models (DSMs) without relying on Ground Control Points (GCPs) measurements. This article focuses specially on the lever-arm calibration part. This proposed calibration method is based on two steps: a first step involves the proper calibration for each sensor, i.e. to determine the position of the optical center of the camera and the GPS antenna phase center in a local coordinate system relative to the sensor. A second step concerns a 3d modeling of the UAV with embedded sensors through a photogrammetric acquisition. Processing this acquisition allows to determine the value of the lever-arm offset without using GCPs.

Research in Biological and Medical Sciences, Including Biochemistry, Communicable Disease and Immunology Internal Medicine, Nuclear Medicine, Physiology, Psychiatry, Surgery, and Veterinary Medicine

DTIC Science & Technology

1976-07-01

aversive stimuli, and activity in a variety of physiological systems implicated in psychosomatic dis- orders. The focus is on arrangement of consequences... activity are held to be linked cen- trally under most conditions. Changes in response to the pre-food stimulus in these DRL animals were less pronounced...individual differences both in autonomic activity and lever-pressing behavior. The to bolst increasi some of the latt the capa with the blood pr

A comparison of the effects of psychotomimetics and anxiolytics on punished and unpunished responding maintained by fixed interval schedules of food reinforcement in the rat.

PubMed

Evenden, John; Duncan, Bertina; Ko, Tracey

2006-02-01

Characterization of anxiolytic drugs often employs conflict paradigms in which the drug effects on punished and unpunished responding can be compared. In this study, a fixed interval schedule generating a range of baseline response rates allowed comparison of the effects of anxiolytic drugs with those of psychotomimetic drugs on equivalent and differing rates of punished and unpunished responding. The first response made by the rat after a 40-s fixed interval elapsed resulted in food pellet delivery. In punished intervals, signalled by the illumination of stimulus lamps above each lever, a 0.6-mA shock was delivered after every 20th response, resulting in a lower rate of responding than that in the unpunished intervals. Three psychotomimetic agents, D-amphetamine, MK801 and DOI were compared with the anxiolytics chlordiazepoxide, NS2710 and pregabalin. The three psychotomimetics preferentially increased rates of unpunished responding compared with those of punished responding. Chlordiazepoxide, NS2710 and, to a lesser extent, pregabalin increased rates of both unpunished and punished responding. In comparison studies, yohimbine also increased rates of both unpunished and punished responding whereas the antidepressant citalopram had no effect. In conclusion, stable baseline performance over many months allowed the direct comparison of several different drugs in the same subjects with no need to adjust shock levels or equate baseline response rates. The drugs had systematic and replicable effects in this procedure, which, in the case of amphetamine and chlordiazepoxide, were similar to those in other species, and psychotomimetic drugs could clearly be distinguished from anxiolytic drugs. The procedure, however, has limited value for characterizing novel anxiolytic agents as the examples used here increased punished and unpunished responding to the same extent, and were indistinguishable in that regard from the clinically anxiogenic agent, yohimbine.

The prepared emotional reflex: intentional preparation of automatic approach and avoidance tendencies as a means to regulate emotional responding.

PubMed

Eder, Andreas B; Rothermund, Klaus; Proctor, Robert W

2010-08-01

Advance preparation of action courses toward emotional stimuli is an effective means to regulate impulsive emotional behavior. Our experiment shows that performing intentional acts of approach and avoidance in an evaluation task influences the unintended activation of approach and avoidance tendencies in another task in which stimulus valence is irrelevant. For the evaluation-relevant blocks, participants received either congruent (positive-approach, negative-avoidance) or incongruent (positive-avoidance, negative-approach) mapping instructions. In the evaluation-irrelevant blocks, approach- and avoidance-related lever movements were selected in response to a stimulus feature other than valence (affective Simon task). Response mapping in the evaluation task influenced performance in the evaluation-irrelevant task: An enhanced affective Simon effect was observed with congruent mapping instructions; in contrast, the effect was reversed when the evaluation task required incongruent responses. Thus, action instructions toward affective stimuli received in one task determined affective response tendencies in another task where these instructions were not in effect. These findings suggest that intentionally prepared short-term links between affective valence and motor responses elicit associated responses without a deliberate act of will, operating like a "prepared reflex." Copyright 2010 APA

Bupropion Attenuates Methamphetamine Self-Administration in Adult Male Rats

PubMed Central

Reichel, Carmela M.; Murray, Jennifer E.; Grant, Kathleen M.; Bevins, Rick A.

2010-01-01

Bupropion is a promising candidate medication for methamphetamine use disorder. As such, we used a preclinical model of drug-taking to determine the effects of bupropion on the reinforcing effects of methamphetamine (0.025, 0.05 or 0.1 mg/kg/infusion). Specificity was determined by investigating the effects of bupropion on responding maintained by sucrose. In the self-administration study, rats were surgically prepared with indwelling jugular catheters and trained to self-administer methamphetamine under an FR5 schedule. A separate group of rats was trained to press a lever for sucrose. Once responding stabilized, rats were pretreated with bupropion (0, 10, 30 and 60 mg/kg IP) 5 min before chamber placement in a unique testing order. Following acute testing, rats were then repeatedly pretreated with 30 and 60 mg/kg bupropion. Acute treatments of bupropion dose dependently reduced drug intake for 0.025 to 0.1 mg/kg methamphetamine; sucrose deliveries were only reduced with the high bupropion dose. Repeated exposure to 60 mg/kg bupropion before the session resulted in a consistent decrease in methamphetamine intake (0.05 and 0.1 mg/kg) and sucrose deliveries. Considered together, this pattern of findings demonstrates that bupropion decreases responding for methamphetamine, but the effects are only somewhat specific. PMID:19010609

Inactivation of the infralimbic prefrontal cortex in rats reduces the influence of inappropriate habitual responding in a response-conflict task.

PubMed

Haddon, J E; Killcross, S

2011-12-29

Previous research suggests the infralimbic cortex is important in situations when there is competition between goal-directed and habitual responding. Here we used a response conflict procedure to further explore the involvement of the infralimbic cortex in this relationship. Rats received training on two instrumental biconditional discriminations, one auditory and one visual, in two distinct contexts. One discrimination was "over-trained" relative to the other, "under-trained," discrimination in the ratio 3:1. At test, animals were presented with incongruent audiovisual stimulus compounds of the training stimuli in the under-trained context. The stimulus elements of these test compounds have previously dictated different lever press responses during training. Rats receiving control infusions into the infralimbic cortex showed a significant interference effect, producing more responses to the over-trained (habitual), but context-inappropriate, stimulus element of the incongruent compound. This interference effect was abolished by inactivation of the infralimbic cortex; animals showed a reduced tendency to produce the habitual but inappropriate response compared with animals receiving control infusions. This finding provides evidence that the infralimbic cortex is involved in attenuating the influence of goal-directed behavior, for example context-appropriate responding. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Responding for sucrose and wheel-running reinforcement: effect of pre-running.

PubMed

Belke, Terry W

2006-01-10

Six male albino Wistar rats were placed in running wheels and exposed to a fixed interval 30-s schedule that produced either a drop of 15% sucrose solution or the opportunity to run for 15s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. To assess the effect of pre-running, animals were allowed to run for 1h prior to a session of responding for sucrose and running. Results showed that, after pre-running, response rates in the later segments of the 30-s schedule decreased in the presence of a wheel-running stimulus and increased in the presence of a sucrose stimulus. Wheel-running rates were not affected. Analysis of mean post-reinforcement pauses (PRP) broken down by transitions between successive reinforcers revealed that pre-running lengthened pausing in the presence of the stimulus signaling wheel running and shortened pauses in the presence of the stimulus signaling sucrose. No effect was observed on local response rates. Changes in pausing in the presence of stimuli signaling the two reinforcers were consistent with a decrease in the reinforcing efficacy of wheel running and an increase in the reinforcing efficacy of sucrose. Pre-running decreased motivation to respond for running, but increased motivation to work for food.

Well below 2 °C: Mitigation strategies for avoiding dangerous to catastrophic climate changes

NASA Astrophysics Data System (ADS)

Xu, Yangyang; Ramanathan, Veerabhadran

2017-09-01

The historic Paris Agreement calls for limiting global temperature rise to “well below 2 °C.” Because of uncertainties in emission scenarios, climate, and carbon cycle feedback, we interpret the Paris Agreement in terms of three climate risk categories and bring in considerations of low-probability (5%) high-impact (LPHI) warming in addition to the central (˜50% probability) value. The current risk category of dangerous warming is extended to more categories, which are defined by us here as follows: >1.5 °C as dangerous; >3 °C as catastrophic; and >5 °C as unknown, implying beyond catastrophic, including existential threats. With unchecked emissions, the central warming can reach the dangerous level within three decades, with the LPHI warming becoming catastrophic by 2050. We outline a three-lever strategy to limit the central warming below the dangerous level and the LPHI below the catastrophic level, both in the near term (<2050) and in the long term (2100): the carbon neutral (CN) lever to achieve zero net emissions of CO2, the super pollutant (SP) lever to mitigate short-lived climate pollutants, and the carbon extraction and sequestration (CES) lever to thin the atmospheric CO2 blanket. Pulling on both CN and SP levers and bending the emissions curve by 2020 can keep the central warming below dangerous levels. To limit the LPHI warming below dangerous levels, the CES lever must be pulled as well to extract as much as 1 trillion tons of CO2 before 2100 to both limit the preindustrial to 2100 cumulative net CO2 emissions to 2.2 trillion tons and bend the warming curve to a cooling trend.

Quantifying Social Motivation in Mice Using Operant Conditioning.

PubMed

Martin, Loren; Iceberg, Erica

2015-08-08

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered shuttle boxes were equipped with two operant levers (left and right) and a food receptacle in one chamber, which was then divided from the second chamber by an automated guillotine door covered by a wire grid. Different stimulus mice, rotated across testing days, served as a social stimulus behind the wire grid, and were only visible following the opening of the guillotine door. Test mice were trained to lever press in order to open the door and gain access to the stimulus partner for 15 sec. The number of lever presses required to obtain the social reward progressively increased on a fixed schedule of 3. Testing sessions ended after test mice stopped lever pressing for 5 consecutive minutes. The last reinforced ratio or breakpoint can be used as a quantitative measure of social motivation. For the second paradigm, test mice were trained to discriminate between left and right lever presses in order to obtain either a food reward or the social reward. Mice were rewarded for every 3 presses of each respective lever. The number of food and social rewards can be compared as a measurement of the value placed upon each reward. The ratio of each reward type can also be compared between mouse strains and the change in this ratio can be monitored within testing sessions to measure satiation with a given reward type. Both of these operant conditioning paradigms are highly useful for the quantification of social motivation in mouse models of autism and other disorders of social behavior.

Probing muscle myosin motor action: x-ray (m3 and m6) interference measurements report motor domain not lever arm movement.

PubMed

Knupp, Carlo; Offer, Gerald; Ranatunga, K W; Squire, John M

2009-07-10

The key question in understanding how force and movement are produced in muscle concerns the nature of the cyclic interaction of myosin molecules with actin filaments. The lever arm of the globular head of each myosin molecule is thought in some way to swing axially on the actin-attached motor domain, thus propelling the actin filament past the myosin filament. Recent X-ray diffraction studies of vertebrate muscle, especially those involving the analysis of interference effects between myosin head arrays in the two halves of the thick filaments, have been claimed to prove that the lever arm moves at the same time as the sliding of actin and myosin filaments in response to muscle length or force steps. It was suggested that the sliding of myosin and actin filaments, the level of force produced and the lever arm angle are all directly coupled and that other models of lever arm movement will not fit the X-ray data. Here, we show that, in addition to interference across the A-band, which must be occurring, the observed meridional M3 and M6 X-ray intensity changes can all be explained very well by the changing diffraction effects during filament sliding caused by heads stereospecifically attached to actin moving axially relative to a population of detached or non-stereospecifically attached heads that remain fixed in position relative to the myosin filament backbone. Crucially, and contrary to previous interpretations, the X-ray interference results provide little direct information about the position of the myosin head lever arm; they are, in fact, reporting relative motor domain movements. The implications of the new interpretation are briefly assessed.

Well below 2 °C: Mitigation strategies for avoiding dangerous to catastrophic climate changes.

PubMed

Xu, Yangyang; Ramanathan, Veerabhadran

2017-09-26

The historic Paris Agreement calls for limiting global temperature rise to "well below 2 °C." Because of uncertainties in emission scenarios, climate, and carbon cycle feedback, we interpret the Paris Agreement in terms of three climate risk categories and bring in considerations of low-probability (5%) high-impact (LPHI) warming in addition to the central (∼50% probability) value. The current risk category of dangerous warming is extended to more categories, which are defined by us here as follows: >1.5 °C as dangerous; >3 °C as catastrophic; and >5 °C as unknown, implying beyond catastrophic, including existential threats. With unchecked emissions, the central warming can reach the dangerous level within three decades, with the LPHI warming becoming catastrophic by 2050. We outline a three-lever strategy to limit the central warming below the dangerous level and the LPHI below the catastrophic level, both in the near term (<2050) and in the long term (2100): the carbon neutral (CN) lever to achieve zero net emissions of CO 2 , the super pollutant (SP) lever to mitigate short-lived climate pollutants, and the carbon extraction and sequestration (CES) lever to thin the atmospheric CO 2 blanket. Pulling on both CN and SP levers and bending the emissions curve by 2020 can keep the central warming below dangerous levels. To limit the LPHI warming below dangerous levels, the CES lever must be pulled as well to extract as much as 1 trillion tons of CO 2 before 2100 to both limit the preindustrial to 2100 cumulative net CO 2 emissions to 2.2 trillion tons and bend the warming curve to a cooling trend. Copyright © 2017 the Author(s). Published by PNAS.

Determinants of reinforcer accumulation during an operant task.

PubMed

McFarland, J M; Lattal, K A

2001-11-01

Responses by rats on an earn lever made available food pellets that were delivered to a food cup by responses on a second, collect, lever. The rats could either collect and immediately consume or accumulate (defined as the percentage of multiple earn responses and as the number of pellets earned before a collect response) earned pellets. In Experiment 1, accumulation varied as a function of variations in the earn or collect response requirements and whether the earn and collect levers were proximal (31 cm) or distal (248 cm) to one another. Some accumulation occurred under all but one of the conditions, but generally was higher when the earn and collect levers were distal to one another, particularly when the earn response requirement was fixed-ratio (FR) 1. In Experiment 2, the contributions of responses and time to accumulation were assessed by comparing an FR 20 earn response requirement to a condition in which only a single earn response was required at the end of a time interval nominally yoked to the FR interval. When 248 cm separated the earn and collect levers, accumulation was always greater in the FR condition, and it was not systematically related to reinforcement rate. In Experiment 3, increasing the earn response requirement with a progressive-ratio schedule that reset only with a collect response increased the likelihood of accumulation when the collect and earn levers were 248 cm apart, even though such accumulation increased the next earn response requirement. Reinforcer accumulation is an understudied dimension of operant behavior that relates to the analysis of such phenomena as hoarding and self-control, in that they too involve accumulating versus immediately collecting or consuming reinforcers.

Determinants of reinforcer accumulation during an operant task.

PubMed Central

McFarland, J M; Lattal, K A

2001-01-01

Responses by rats on an earn lever made available food pellets that were delivered to a food cup by responses on a second, collect, lever. The rats could either collect and immediately consume or accumulate (defined as the percentage of multiple earn responses and as the number of pellets earned before a collect response) earned pellets. In Experiment 1, accumulation varied as a function of variations in the earn or collect response requirements and whether the earn and collect levers were proximal (31 cm) or distal (248 cm) to one another. Some accumulation occurred under all but one of the conditions, but generally was higher when the earn and collect levers were distal to one another, particularly when the earn response requirement was fixed-ratio (FR) 1. In Experiment 2, the contributions of responses and time to accumulation were assessed by comparing an FR 20 earn response requirement to a condition in which only a single earn response was required at the end of a time interval nominally yoked to the FR interval. When 248 cm separated the earn and collect levers, accumulation was always greater in the FR condition, and it was not systematically related to reinforcement rate. In Experiment 3, increasing the earn response requirement with a progressive-ratio schedule that reset only with a collect response increased the likelihood of accumulation when the collect and earn levers were 248 cm apart, even though such accumulation increased the next earn response requirement. Reinforcer accumulation is an understudied dimension of operant behavior that relates to the analysis of such phenomena as hoarding and self-control, in that they too involve accumulating versus immediately collecting or consuming reinforcers. PMID:11768714

Well below 2 °C: Mitigation strategies for avoiding dangerous to catastrophic climate changes

PubMed Central

Xu, Yangyang; Ramanathan, Veerabhadran

2017-01-01

The historic Paris Agreement calls for limiting global temperature rise to “well below 2 °C.” Because of uncertainties in emission scenarios, climate, and carbon cycle feedback, we interpret the Paris Agreement in terms of three climate risk categories and bring in considerations of low-probability (5%) high-impact (LPHI) warming in addition to the central (∼50% probability) value. The current risk category of dangerous warming is extended to more categories, which are defined by us here as follows: >1.5 °C as dangerous; >3 °C as catastrophic; and >5 °C as unknown, implying beyond catastrophic, including existential threats. With unchecked emissions, the central warming can reach the dangerous level within three decades, with the LPHI warming becoming catastrophic by 2050. We outline a three-lever strategy to limit the central warming below the dangerous level and the LPHI below the catastrophic level, both in the near term (<2050) and in the long term (2100): the carbon neutral (CN) lever to achieve zero net emissions of CO2, the super pollutant (SP) lever to mitigate short-lived climate pollutants, and the carbon extraction and sequestration (CES) lever to thin the atmospheric CO2 blanket. Pulling on both CN and SP levers and bending the emissions curve by 2020 can keep the central warming below dangerous levels. To limit the LPHI warming below dangerous levels, the CES lever must be pulled as well to extract as much as 1 trillion tons of CO2 before 2100 to both limit the preindustrial to 2100 cumulative net CO2 emissions to 2.2 trillion tons and bend the warming curve to a cooling trend. PMID:28912354

Rimonabant’s Reductive Effects on High Densities of Food Reinforcement, but not Palatability, in Lean and Obese Zucker Rats

PubMed Central

Buckley, Jessica Lynn; Rasmussen, Erin B.

2014-01-01

Rationale Cannabinoid antagonists purportedly have greater effects in reducing the intake of highly palatable food compared to less palatable food. However, this assertion is based on free-feeding studies in which the amount of palatable food eaten under baseline conditions is often confounded with other variables, such as unequal access to both food options and differences in qualitative features of the foods. Objective We attempted to reduce these confounds by using a model of choice that programmed the delivery rates of sucrose and carrot-flavored pellets. Methods Lever-pressing of ten lean (Fa/Fa or Fa/fa) and ten obese (fa/fa) Zucker rats was placed under three conditions in which programmed ratios for food pellets on two levers were 5:1, 1:1, and 1:5. In Phase 1, responses on the two levers produced one type of pellet (sucrose or carrot); in Phase 2, responses on one lever produced sucrose pellets and on the other lever produced carrot pellets. After responses stabilized under each food ratio, acute doses of rimonabant (0, 3, and 10 mg/kg) were administered before experimental sessions. The number of reinforcers and responses earned per session under each ratio and from each lever was compared. Results and Conclusions Rimonabant reduced reinforcers in 1:5 and 5:1 food ratios in Phase 1, and across all ratios in Phase 2. Rimonabant reduced sucrose and carrot-flavored pellet consumption similarly; rimonabant did not affect bias toward sucrose, but increased sensitivity to amount differences in lean rats. This suggests that relative amount of food, not palatability, may be an important behavioral mechanism in the effects of rimonabant. PMID:24398820

Rimonabant's reductive effects on high densities of food reinforcement, but not palatability, in lean and obese Zucker rats.

PubMed

Buckley, Jessica L; Rasmussen, Erin B

2014-05-01

Cannabinoid antagonists purportedly have greater effects in reducing the intake of highly palatable food compared to less palatable food. However, this assertion is based on free-feeding studies in which the amount of palatable food eaten under baseline conditions is often confounded with other variables, such as unequal access to both food options and differences in qualitative features of the foods. We attempted to reduce these confounds by using a model of choice that programmed the delivery rates of sucrose and carrot-flavored pellets. Lever pressing of ten lean (Fa/Fa or Fa/fa) and ten obese (fa/fa) Zucker rats was placed under three conditions in which programmed ratios for food pellets on two levers were 5:1, 1:1, and 1:5. In phase 1, responses on the two levers produced one type of pellet (sucrose or carrot); in phase 2, responses on one lever produced sucrose pellets and on the other lever produced carrot pellets. After responses stabilized under each food ratio, acute doses of rimonabant (0, 3, and 10 mg/kg) were administered before experimental sessions. The number of reinforcers and responses earned per session under each ratio and from each lever was compared. Rimonabant reduced reinforcers in 1:5 and 5:1 food ratios in phase 1, and across all ratios in phase 2. Rimonabant reduced sucrose and carrot-flavored pellet consumption similarly; rimonabant did not affect bias toward sucrose, but increased sensitivity to amount differences in lean rats. This suggests that relative amount of food, not palatability, may be an important behavioral mechanism in the effects of rimonabant.

Electron microscopic evidence for the myosin head lever arm mechanism in hydrated myosin filaments using the gas environmental chamber

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minoda, Hiroki; CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012; Okabe, Tatsuhiro

2011-02-25

Research highlights: {yields} We succeeded in recording structural changes of hydrated myosin cross-bridges. {yields} We succeeded in position-marking the cross-bridges with site-directed antibodies. {yields} We recorded cross-bridge movement at different regions in individual cross-bridge. {yields} The movement was smallest at the cross-bridge-subfragment two boundary. {yields} The results provide evidence for the cross-bridge lever arm mechanism. -- Abstract: Muscle contraction results from an attachment-detachment cycle between the myosin heads extending from myosin filaments and the sites on actin filaments. The myosin head first attaches to actin together with the products of ATP hydrolysis, performs a power stroke associated with release ofmore » hydrolysis products, and detaches from actin upon binding with new ATP. The detached myosin head then hydrolyses ATP, and performs a recovery stroke to restore its initial position. The strokes have been suggested to result from rotation of the lever arm domain around the converter domain, while the catalytic domain remains rigid. To ascertain the validity of the lever arm hypothesis in muscle, we recorded ATP-induced movement at different regions within individual myosin heads in hydrated myosin filaments, using the gas environmental chamber attached to the electron microscope. The myosin head were position-marked with gold particles using three different site-directed antibodies. The amplitude of ATP-induced movement at the actin binding site in the catalytic domain was similar to that at the boundary between the catalytic and converter domains, but was definitely larger than that at the regulatory light chain in the lever arm domain. These results are consistent with the myosin head lever arm mechanism in muscle contraction if some assumptions are made.« less

Disconnection of basolateral amygdala and insular cortex disrupts conditioned approach in Pavlovian lever autoshaping.

PubMed

Nasser, Helen M; Lafferty, Danielle S; Lesser, Ellen N; Bacharach, Sam Z; Calu, Donna J

2018-01-01

Previously established individual differences in appetitive approach and devaluation sensitivity observed in goal- and sign-trackers may be attributed to differences in the acquisition, modification, or use of associative information in basolateral amygdala (BLA) pathways. Here, we sought to determine the extent to which communication of associative information between BLA and anterior portions of insular cortex (IC) supports ongoing Pavlovian conditioned approach behaviors in sign- and goal-tracking rats, in the absence of manipulations to outcome value. We hypothesized that the BLA mediates goal-, but not sign- tracking approach through interactions with the IC, a brain region involved in supporting flexible behavior. We first trained rats in Pavlovian lever autoshaping to determine their sign- or goal-tracking tendency. During alternating test sessions, we gave unilateral intracranial injections of vehicle or a cocktail of gamma-aminobutyric acid (GABA) receptor agonists, baclofen and muscimol, unilaterally into the BLA and contralaterally or ipsilaterally into the IC prior to reinforced lever autoshaping sessions. Consistent with our hypothesis we found that contralateral inactivation of BLA and IC increased the latency to approach the food cup and decreased the number of food cup contacts in goal-trackers. While contralateral inactivation of BLA and IC did not affect the total number of lever contacts in sign-trackers, this manipulation increased the latency to approach the lever. Ipsilateral inactivation of BLA and IC did not impact approach behaviors in Pavlovian lever autoshaping. These findings, contrary to our hypothesis, suggest that communication between BLA and IC maintains a representation of initially learned appetitive associations that commonly support the initiation of Pavlovian conditioned approach behavior regardless of whether it is directed at the cue or the location of reward delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

Inactivation of the central nucleus of the amygdala reduces the effect of punishment on cocaine self-administration in rats.

PubMed

Xue, YueQiang; Steketee, Jeffery D; Sun, WenLin

2012-03-01

Continued cocaine use despite the negative consequences is a hallmark of cocaine addiction. One such consequence is punishment, which is often used by society to curb cocaine use. Unfortunately, we know little about the mechanism involved in regulation by punishment of cocaine use. The fact that cocaine addicts continue to use cocaine despite potentially severe punishment suggests that the mechanism may be impaired. Such impairment is expected to critically contribute to compulsive cocaine use. This study was aimed at testing the hypothesis that the central nucleus of the amygdala (CeN) plays a critical role in such regulation. To this end, rats were trained to press a lever to self-administer cocaine under a chained schedule: a response on one lever (cocaine-seeking lever) led to access to the other lever (cocaine-taking lever), on which a response was reinforced by cocaine and cues. Thereafter, responses on the seeking lever were punished by footshock with a probability of 0.5. Cocaine self-administration (SA) was significantly suppressed by punishment in an intensity-dependent manner. Interestingly, rats trained with daily 6-h (extended access) but not 2-h (limited access) sessions showed resistance to the lower intensity of punishment. Inactivation of the CeN induced a robust anti-punishment effect in both groups. These data provided evidence that the CeN is a critical neural substrate involved in regulation by punishment of cocaine SA. Rats with a history of extended cocaine SA appeared to be less sensitive to punishment. The decreased sensitivity could result from the neuroplastic changes induced by extended cocaine SA in the CeN. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Inactivation of the central nucleus of the amygdala reduces the effect of punishment on cocaine self-administration in rats

PubMed Central

Xue, YueQiang; Steketee, Jeffery D.; Sun, WenLin

2012-01-01

Continued cocaine use despite the negative consequences is a hallmark of cocaine addiction. One such consequence is punishment that is often used by society to curb cocaine use. Unfortunately, we know little about the mechanism involved in regulation by punishment of cocaine use. The fact that cocaine addicts continue cocaine use despite potential severe punishment suggests that the mechanism may be impaired. Such impairment is expected to critically contribute to compulsive cocaine use. This study aimed to test the hypothesis that the central nucleus of amygdala (CeN) plays a critical role in such regulation. To this end, rats were trained to press a lever to self-administer cocaine under a chained schedule: a response on one lever (cocaine-seeking lever) led to access to the other lever (cocaine-taking lever) on which a response was reinforced by cocaine and cues. Thereafter, responses on the seeking lever were punished by footshock with a probability of 0.5. Cocaine self-administration (SA) was significantly suppressed by punishment in an intensity-dependent manner. Interestingly, rats trained with daily 6-h (extended access) but not 2-h (limited access) sessions showed resistance to the lower intensity of punishment. Inactivation of the CeN induced a robust anti-punishment effect in both groups. These data provided evidence that the CeN is a critical neural substrate involved in regulation by punishment of cocaine SA. Rats with a history of extended cocaine SA appeared to be less sensitive to punishment. The decreased sensitivity could result from the neuroplastic changes induced by extended cocaine SA in the CeN. PMID:22304754

Ethanol-reinforced responding by AA and ANA rats following the sucrose-substitution initiation procedure.

PubMed

Files, F J; Denning, C E; Hyytia, P; Kiianmaa, K; Samson, H H

1997-06-01

Ethanol-reinforced responding was initiated in male AA and ANA rats using the sucrose-substitution procedure. Before the initiation procedure, a homecage, two-bottle preference test was conducted. The rats were then trained to respond on an Fixed-Ratio 1 schedule with sucrose reinforcement. Over sessions, ethanol was added gradually to the sucrose solution as the concentration of sucrose was reduced until 10% ethanol (v/v) alone functioned as the reinforcer for lever pressing. The schedule of reinforcement was then increased to Fixed-Ratio 4. Next, the ethanol concentration presented as the reinforcer was increased over weeks to 15%, 20%, 30%, and then returned to 10%. A second homecage test was then performed. The results showed that the AA and ANA lines differed significantly on preference and intake (g/kg) during the homecage preference tests. There was a significant increase in preference during the second homecage test. During sucrose substitution, initial large differences in responding were observed between the lines. When the ethanol concentration was increased, intake (grams per kilogram) increased for the AA line but not for the ANA line. These effects were a function of no change in responding by the AA rats as concentration was increased and a decrease in responding by the ANA rats at the higher concentrations (20% and 30%). Taken together, data indicate that ethanol can function as a positive reinforcer for the behavior of AA and ANA rats. Even though 10% ethanol functioned as a reinforcer similarly for the two lines, ethanol intake in the AA line was significantly greater at the higher concentrations of ethanol, suggesting that ethanol functioned as a qualitatively different reinforcer for the AA rats, compared with the ANA rats.

A strong static-magnetic field alters operant responding by rats.

PubMed

Nakagawa, M; Matsuda, Y

1988-01-01

Forty male rats of the Wistar ST strain were trained and observed for Sidman avoidance (SA) for 7 weeks or for discriminative avoidance (DA) for 14 weeks to determine the effects of exposure to a strong static-magnetic field. Before avoidance conditioning was completed, rats in the SA group were exposed to the static field at 0.6 T, 16 h/day for 4 days during the fifth week, and those in the DA group were exposed for 6 h/day for 4 days during the seventh week. In the SA conditioning, frequency of lever-pressing by exposed rats gradually decreased during 1 week of exposure and stayed low for at least 2 weeks after exposure. Frequencies of electric shocks received by the rats increased dramatically during the second day of exposure and consistently stayed higher than those of control rats. In the DA condition, exposed rats responded at lower rates than did control rats throughout the observation period. They received more shocks during the 2 weeks following exposure. The data indicate that performance of avoidance responses was inhibited by a comparatively long exposure to a strong magnetic field.

Responding for sucrose and wheel-running reinforcement: effect of D-amphetamine.

PubMed

Belke, T W; Oldford, A C; Forgie, M Y; Beye, J A

2005-07-01

The present study assessed the effect of D-amphetamine on responding maintained by wheel-running and sucrose reinforcement. Six male albino Wistar rats were placed in running wheels and exposed to a fixed-interval 30-s schedule that produced either a drop of 5% sucrose solution or the opportunity to run for 15 s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. Doses of 0.25, 0.5, 1.0, 1.5, and 3.0 mg/kg D-amphetamine were administered by i.p. injection 20 min prior to a session. As the dose increased, index of curvature values decreased toward zero and rate-dependency plots revealed increases in lower rates early in the interval and decreases in higher rates toward the end of the interval. Effects were similar in the presence of both stimuli. However, an analysis of post-reinforcement pauses and local response rates broken down by transitions revealed a differential effect. As the dose increased, local response rates following a wheel-running reinforcer were affected more than those following a sucrose reinforcer.

(-)Ephedrine and caffeine mutually potentiate one another's amphetamine-like stimulus effects.

PubMed

Young, R; Gabryszuk, M; Glennon, R A

1998-10-01

Using rats trained to discriminate 1 mg/kg of (+)amphetamine (ED50 = 0.4 mg/kg) from saline vehicle in a two-lever drug discrimination procedure, it was shown that (-)ephedrine (ED50 = 4.5 mg/kg), but not (+)ephedrine, substitutes for the (+)AMPH stimulus. It was also shown that caffeine (ED50 = 12.9 mg/kg) can substitute for (+)amphetamine in a dose-related fashion. Doses of (-)ephedrine and caffeine, which produced < or = 1% drug-appropriate responding when administered alone, were able to enhance each other's stimulus effects when administered in combination such that there was a twofold leftward shift in their respective dose-response curves. Furthermore, stimulus generalization occurred when a dose of caffeine that produced saline-appropriate responding when administered alone was administered in combination with (+)ephedrine. It would appear that low doses of (-)ephedrine and caffeine may mutually potentiate one another's stimulus effects in (+)AMPH-trained rats, and that a combination of caffeine and (+)ephedrine result in altered stimulus character when compared to comparable doses of either agent administered alone.

Face-Sealing Butterfly Valve

NASA Technical Reports Server (NTRS)

Tervo, John N.

1992-01-01

Valve plate made to translate as well as rotate. Valve opened and closed by turning shaft and lever. Interactions among lever, spring, valve plate, and face seal cause plate to undergo combination of translation and rotation so valve plate clears seal during parts of opening and closing motions.

The structure of affective action representations: temporal binding of affective response codes.

PubMed

Eder, Andreas B; Müsseler, Jochen; Hommel, Bernhard

2012-01-01

Two experiments examined the hypothesis that preparing an action with a specific affective connotation involves the binding of this action to an affective code reflecting this connotation. This integration into an action plan should lead to a temporary occupation of the affective code, which should impair the concurrent representation of affectively congruent events, such as the planning of another action with the same valence. This hypothesis was tested with a dual-task setup that required a speeded choice between approach- and avoidance-type lever movements after having planned and before having executed an evaluative button press. In line with the code-occupation hypothesis, slower lever movements were observed when the lever movement was affectively compatible with the prepared evaluative button press than when the two actions were affectively incompatible. Lever movements related to approach and avoidance and evaluative button presses thus seem to share a code that represents affective meaning. A model of affective action control that is based on the theory of event coding is discussed.

Sign-tracking (autoshaping) in rats: a comparison of cocaine and food as unconditioned stimuli.

PubMed

Kearns, David N; Weiss, Stanley J

2004-11-01

A series of experiments was performed to determine whether sign-tracking would occur in rats with intravenous (i.v.) cocaine as the unconditioned stimulus. In Experiment 1, a retractable lever paired with food produced strong sign-tracking, but a lever paired with one of three doses of i.v. cocaine did not elicit any approach or contact behavior. Experiment 2 demonstrated that doses of cocaine that did not elicit sign-tracking would function as a positive reinforcer for a lever contact operant. In Experiment 3, an artificial consummatory response was added to make the cocaine reinforcement episode more behaviorally comparable to that occasioned by food. Although the rats readily performed this response when it was required to receive cocaine infusions, they still did not contact a lever that signaled the availability of these infusions. It appears that cocaine is different from other positive reinforcers (e.g., food, water, warmth, or intracranial stimulation) in that it will not produce sign-tracking in rats.

Effect of wheelchair design on wheeled mobility and propulsion efficiency in less-resourced settings

PubMed Central

2017-01-01

Background Wheelchair research includes both qualitative and quantitative approaches, primarily focuses on functionality and skill performance and is often limited to short testing periods. This is the first study to use the combination of a performance test (i.e. wheelchair propulsion test) and a multiple-day mobility assessment to evaluate wheelchair designs in rural areas of a developing country. Objectives Test the feasibility of using wheel-mounted accelerometers to document bouts of wheeled mobility data in rural settings and use these data to compare how patients respond to different wheelchair designs. Methods A quasi-experimental, pre- and post-test design was used to test the differences between locally manufactured wheelchairs (push rim and tricycle) and an imported intervention product (dual-lever propulsion wheelchair). A one-way repeated measures analysis of variance was used to interpret propulsion and wheeled mobility data. Results There were no statistical differences in bouts of mobility between the locally manufactured and intervention product, which was explained by high amounts of variability within the data. With regard to the propulsion test, push rim users were significantly more efficient when using the intervention product compared with tricycle users. Conclusion Use of wheel-mounted accelerometers as a means to test user mobility proved to be a feasible methodology in rural settings. Variability in wheeled mobility data could be decreased with longer acclimatisation periods. The data suggest that push rim users experience an easier transition to a dual-lever propulsion system. PMID:28936416

Investigation of impulsivity in binge-eating rats in a delay-discounting task and its prevention by the d-amphetamine prodrug, lisdexamfetamine.

PubMed

Vickers, Steven P; Goddard, Simon; Brammer, Richard J; Hutson, Peter H; Heal, David J

2017-06-01

Freely-fed, female, rats were trained in a two-lever, delay-discounting task: one lever delivered a single chocolate-flavoured pellet immediately and the other a three-pellet reward after increasing delay (0, 4, 8, 16, 32 s). Rats were divided into two groups (i.e. binge-eating rats given irregular, limited access to chocolate in addition to normal chow and controls maintained on normal chow). Both groups exhibited increased preference for the immediate reward as the delay interval was lengthened. The discounting rate was significantly greater in binge-eating rats than non-binge-eating controls, especially as the behaviour became more established indicating that increased impulsivity and intolerance of delayed reward are part of the psychopathology of binge-eating. Lisdexamfetamine (0.8 mg/kg, orally ( d-amphetamine base)) reversed the reduced preference of binge-eating rats for larger rewards at delay intervals of 4 s, 8 s and 32 s and across all sessions. Lisdexamfetamine-treated binge-eating rats consumed the same number of pellets as vehicle-treated, binge-eating rats and non-binge-eating controls eliminating the possibility lisdexamfetamine's actions on appetite or satiety mediated its effects on operant responding for food pellets in delay-discounting. In summary, binge-eating rats showed increased impulsive choice compared with non-binge-eating controls that was reversed by lisdexamfetamine, complementing results showing lisdexamfetamine reduced impulsiveness scores in patients with binge-eating disorder.

Effect of wheelchair design on wheeled mobility and propulsion efficiency in less-resourced settings.

PubMed

Stanfill, Christopher J; Jensen, Jody L

2017-01-01

Wheelchair research includes both qualitative and quantitative approaches, primarily focuses on functionality and skill performance and is often limited to short testing periods. This is the first study to use the combination of a performance test (i.e. wheelchair propulsion test) and a multiple-day mobility assessment to evaluate wheelchair designs in rural areas of a developing country. Test the feasibility of using wheel-mounted accelerometers to document bouts of wheeled mobility data in rural settings and use these data to compare how patients respond to different wheelchair designs. A quasi-experimental, pre- and post-test design was used to test the differences between locally manufactured wheelchairs (push rim and tricycle) and an imported intervention product (dual-lever propulsion wheelchair). A one-way repeated measures analysis of variance was used to interpret propulsion and wheeled mobility data. There were no statistical differences in bouts of mobility between the locally manufactured and intervention product, which was explained by high amounts of variability within the data. With regard to the propulsion test, push rim users were significantly more efficient when using the intervention product compared with tricycle users. Use of wheel-mounted accelerometers as a means to test user mobility proved to be a feasible methodology in rural settings. Variability in wheeled mobility data could be decreased with longer acclimatisation periods. The data suggest that push rim users experience an easier transition to a dual-lever propulsion system.

Effects of D-cycloserine on the extinction of appetitive operant learning.

PubMed

Vurbic, Drina; Gold, Benjamin; Bouton, Mark E

2011-08-01

Four experiments with rat subjects examined whether D-cycloserine (DCS), a partial NMDA agonist, facilitates the extinction of operant lever-pressing reinforced by food. Previous research has demonstrated that DCS facilitates extinction learning with methods that involve Pavlovian extinction. In the current experiments, operant conditioning occurred in Context A, extinction in Context B, and then testing occurred in both the extinction and conditioning contexts. Experiments 1A and 1B tested the effects of three doses of DCS (5, 15, and 30 mg/kg) on the extinction of lever pressing trained as a free operant. Experiment 2 examined their effects when extinction of the free operant was conducted in the presence of nonresponse-contingent deliveries of the reinforcer (that theoretically reduced the role of generalization decrement in suppressing responding). Experiment 3 examined their effects on extinction of a discriminated operant, that is, one that had been reinforced in the presence of a discriminative stimulus, but not in its absence. A strong ABA renewal effect was observed in all four experiments during testing. However, despite the use of DCS doses and a drug administration procedure that facilitates the extinction of Pavlovian learning, there was no evidence in any experiment that DCS facilitated operant extinction learning assessed in either the extinction or the conditioning context. DCS may primarily facilitate learning processes that underlie Pavlovian, rather than purely operant, extinction. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Does addressing gender inequalities and empowering women and girls improve health and development programme outcomes?

PubMed

Taukobong, Hannah F G; Kincaid, Mary M; Levy, Jessica K; Bloom, Shelah S; Platt, Jennifer L; Henry, Sarah K; Darmstadt, Gary L

2016-12-01

This article presents evidence supporting the hypothesis that promoting gender equality and women's and girls' empowerment (GEWE) leads to better health and development outcomes. We reviewed the literature across six sectors-family planning (FP); maternal, newborn and child health (MNCH); nutrition; agriculture; water, sanitation and hygiene; and financial services for the poor-and found 76 studies from low and middle-income countries that met our inclusion criteria. Across these studies, we identified common GEWE variables that emerged repeatedly as significant predictors of sector outcomes. We grouped these variables into 10 thematic categories, which we termed 'gender-related levers'. These levers were then classified by the strength of evidence into Wedges, Foundations and Facilitators. Wedges are gender-related levers that had strong associations with improved outcomes across multiple sectors. They include: 'control over income/assets/resources', 'decision-making power' and 'education'. Elements of these levers overlap, but combined, they encapsulate agency. Increasing female agency promotes equality and broadly improves health and development for women, their families and their communities. The second classification, Foundations, displayed strong, positive associations across FP, MNCH and nutrition. Foundations have a more proximal relationship with sector outcomes and include: 'equitable interpersonal relationships', 'mobility' and 'personal safety'. Finally, the third group of levers, Facilitators, was associated with improved outcomes in two to three sectors and include: 'access to information', 'community groups', 'paid labour' and 'rights'. These levers make it easier for women and girls to achieve their goals and are more traditional elements of development programmes. Overall, gender-related levers were associated with improvements in a variety of health and development outcomes. Furthermore, these associations were cross-sectoral, suggesting that to fully realize the benefits of promoting GEWE, the development community must collaborate in co-ordinated and integrated ways across multiple sectors. More research is needed to identify the mechanisms by which gendered interventions work and under what circumstances. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline.

PubMed

Swalve, Natashia; Smethells, John R; Carroll, Marilyn E

2016-07-15

Tobacco use is the largest cause of preventable mortality in the western world. Even after treatment, relapse rates for tobacco are high, and more effective pharmacological treatments are needed. Progesterone (PRO), a female hormone used in contraceptives, reduces stimulant use but its effects on tobacco addiction are unknown. Varenicline (VAR) is a commonly used medication that reduces tobacco use. The present study examined sex differences in the individual vs. combined effects of PRO and VAR on reinstatement of nicotine-seeking behavior in a rat model of relapse. Adult female and male Wistar rats self-administered nicotine (NIC, 0.03mg/kg/infusion) for 14days followed by 21days of extinction when no cues or drug were present. Rats were then divided into 4 treatment groups: control (VEH+SAL), PRO alone (PRO+SAL), VAR alone (VEH+VAR) and the combination (PRO+VAR). Reinstatement of nicotine-seeking behavior induced by priming injections of NIC or caffeine (CAF), presentation of cues (CUES), and the combination of drugs and cues (e.g. NIC+CUES, CAF+CUES) were tested after extinction. Male and female rats did not differ in self-administration of nicotine or extinction responding, and both showed elevated levels of responding to the CAF+CUES condition. However, males, but not females, reinstated active lever-pressing to the NIC+CUES condition, and that was attenuated by both VAR and VAR+PRO treatment. Thus, males were more sensitive to NIC+CUE-induced reinstatement than females, and VAR alone and VAR combined with PRO effectively reduced nicotine relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

Compound stimulus presentation and the norepinephrine reuptake inhibitor atomoxetine enhance long-term extinction of cocaine-seeking behavior.

PubMed

Janak, Patricia H; Bowers, M Scott; Corbit, Laura H

2012-03-01

Drug abstinence is frequently compromised when addicted individuals are re-exposed to environmental stimuli previously associated with drug use. Research with human addicts and in animal models has demonstrated that extinction learning (non-reinforced cue-exposure) can reduce the capacity of such stimuli to induce relapse, yet extinction therapies have limited long-term success under real-world conditions (Bouton, 2002; O'Brien, 2008). We hypothesized that enhancing extinction would reduce the later ability of drug-predictive cues to precipitate drug-seeking behavior. We, therefore, tested whether compound stimulus presentation and pharmacological treatments that augment noradrenergic activity (atomoxetine; norepinephrine reuptake inhibitor) during extinction training would facilitate the extinction of drug-seeking behaviors, thus reducing relapse. Rats were trained that the presentation of a discrete cue signaled that a lever press response would result in cocaine reinforcement. Rats were subsequently extinguished and spontaneous recovery of drug-seeking behavior following presentation of previously drug-predictive cues was tested 4 weeks later. We find that compound stimulus presentations or pharmacologically increasing noradrenergic activity during extinction training results in less future recovery of responding, whereas propranolol treatment reduced the benefit seen with compound stimulus presentation. These data may have important implications for understanding the biological basis of extinction learning, as well as for improving the outcome of extinction-based therapies.

Prosthetic Hand For Holding Rods, Tools, And Handles

NASA Technical Reports Server (NTRS)

Belcher, Jewell G., Jr.; Vest, Thomas W.

1995-01-01

Prosthetic hand with quick-grip/quick-release lever broadens range of specialized functions available to lower-arm amputee by providing improved capabilities for gripping rods, tools, handles, and like. Includes two stationary lower fingers opposed by one pivoting upper finger. Lever operates in conjunction with attached bracket.

Ergonomic evaluation of a mechanical anastomotic stapler used by Japanese surgeons.

PubMed

Kono, Emiko; Tada, Mitsunori; Kouchi, Makiko; Endo, Yui; Tomizawa, Yasuko; Matsuo, Tomoko; Nomura, Sachiyo

2014-06-01

The satisfaction rating of currently available mechanical staplers for Japanese surgeons with small hands is low. To identify the issue, we examined the relationship of hand dimensions and grip force with the operation force of a mechanical circular stapler. Hand dimensions and grip force were measured in 113 Japanese surgeons (52 men and 61 women). We then evaluated the relationship between grip width and the operation force required to push the lever of the stapler, at three points on the lever, using a digital force gauge. The optimal grip width of the dominant hand was 62.5 ± 8.5 mm for men and 55.5 ± 5.9 mm for women (p < 0.001). The maximum grip force of the dominant hand was 44.2 ± 6.1 kg for men and 29.7 ± 4.5 kg for women (p < 0.001) and the maximum operation force required to push the lever 7.0, 45.0, and 73.0 mm from the end of the lever was 21.8, 28.6, and 42.4 kg, respectively. To our knowledge, this is the first ergonomic study of a surgical stapler to be conducted in Asia. Firing the stapler by gripping the proximal side of the lever is physically impossible for most Japanese women surgeons since the required operation force exceeds the maximum grip force, which probably accounts for the stress perceived by these women.

Motivational state and reward content determine choice behavior under risk in mice.

PubMed

Leblond, Mona; Fan, David; Brynildsen, Julia K; Yin, Henry H

2011-01-01

Risk is a ubiquitous feature of the environment for most organisms, who must often choose between a small and certain reward and a larger but less certain reward. To study choice behavior under risk in a genetically well characterized species, we trained mice (C57BL/6) on a discrete trial, concurrent-choice task in which they must choose between two levers. Pressing one lever (safe choice) is always followed by a small reward. Pressing the other lever (risky choice) is followed by a larger reward, but only on some of the trials. The overall payoff is the same on both levers. When mice were not food deprived, they were indifferent to risk, choosing both levers with equal probability regardless of the level of risk. In contrast, following food or water deprivation, mice earning 10% sucrose solution were risk-averse, though the addition of alcohol to the sucrose solution dose-dependently reduced risk aversion, even before the mice became intoxicated. Our results falsify the budget rule in optimal foraging theory often used to explain behavior under risk. Instead, they suggest that the overall demand or desired amount for a particular reward determines risk preference. Changes in motivational state or reward identity affect risk preference by changing demand. Any manipulation that increases the demand for a reward also increases risk aversion, by selectively increasing the frequency of safe choices without affecting frequency of risky choices.

Bidirectional effects of inhibiting or activating NMDA receptors on extinction after cocaine self-administration in rats

PubMed Central

Hafenbreidel, Madalyn; Todd, Carolynn Rafa; Twining, Robert C.; Tuscher, Jennifer J.; Mueller, Devin

2014-01-01

Rationale Extinction of drug seeking is facilitated by NMDA receptor (NMDAr) agonists, but it remains unclear whether extinction is dependent on NMDAr activity. Objectives We investigated the necessity of NMDArs for extinction of cocaine seeking, and whether extinction altered NMDAr expression within extinction-related neuroanatomical loci. Methods Rats were trained to lever press for i.v. infusions of cocaine or sucrose reinforcement prior to extinction training or withdrawal. Results Administration of the NMDAr competitive antagonist CPP prior to four brief extinction sessions impaired subsequent extinction retention. In contrast, post-extinction administration of the NMDAr coagonist D-serine attenuated lever pressing across days as compared to saline administration, indicative of facilitated consolidation of extinction. Furthermore, expression of the NMDAr subunits, GluN2A and GluN2B, was not altered in the ventromedial prefrontal cortex. However, both GluN2A and GluN2B subunit expression in the nucleus accumbens was increased following cocaine self-administration, and this increased expression was relatively resistant to modulation by extinction. Conclusions Our findings demonstrate that extinction of cocaine seeking is bidirectionally mediated by NMDArs and suggest that selective modulation of NMDAr activity could facilitate extinction-based therapies for treatment of cocaine abuse. PMID:24847958

Impulsivity and AMPA receptors: aniracetam ameliorates impulsive behavior induced by a blockade of AMPA receptors in rats.

PubMed

Nakamura, K; Kurasawa, M; Shirane, M

2000-04-17

The study aimed to ascertain the involvement of central AMPA receptors in impulsive behaviors of aged rats and to examine the effects of aniracetam. Premature response in the two-lever choice reaction task was assessed as an index of impulsivity. Intracerebroventricular injection of 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), an AMPA receptor antagonist, dose-dependently (10.1-1009 ng/rat) increased only premature response without altering responding speed and choice accuracy 30 min after the injection. Aniracetam (30 mg/kg p.o.), a positive allosteric modulator of AMPA receptors, or AMPA (55.9 ng/rat, co-injected with NBQX) completely restored the NBQX-induced increase in impulsivity. These results indicate that AMPA receptors are tonically involved in the regulation of impulsivity.

26. VIEW FROM EAST IN BRIDGE TENDER'S HOUSE, LEVERS FOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

26. VIEW FROM EAST IN BRIDGE TENDER'S HOUSE, LEVERS FOR GASOLINE ENGINE OPERATION FOR BRIDGE AND THEIR CONNECTIONS TO CONTROL RODS ON DOWNSTREAM SIDE OF SWING-SPAN; new bridge located in background - Tipers Bridge, Spanning Great Wicomico River at State Route 200, Kilmarnock, Lancaster County, VA

25. VIEW EAST IN BRIDGE TENDER'S HOUSE, (left) ORIGINAL LEVERS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

25. VIEW EAST IN BRIDGE TENDER'S HOUSE, (left) ORIGINAL LEVERS FOR GASOLINE ENGINE OPERATION OF SWING-SPAN, (right) PANEL F ELECTRIC OPERATION OF GATES AND SWING-SPAN; new bridge located in background - Tipers Bridge, Spanning Great Wicomico River at State Route 200, Kilmarnock, Lancaster County, VA

46 CFR 160.035-2 - General requirements for lifeboats.

Code of Federal Regulations, 2011 CFR

2011-10-01

... lever, from the keel to the side bench, shall be painted or otherwise colored white, to provide a contrasting background for the lever. This band of white should be approximately 12 inches wide depending on the internal arrangements of the lifeboat. (d) For the purpose of calculations and conducting tests...

46 CFR 160.035-2 - General requirements for lifeboats.

Code of Federal Regulations, 2010 CFR

2010-10-01

... lever, from the keel to the side bench, shall be painted or otherwise colored white, to provide a contrasting background for the lever. This band of white should be approximately 12 inches wide depending on the internal arrangements of the lifeboat. (d) For the purpose of calculations and conducting tests...

The Relationship between State Policy Levers and Student Mobility

ERIC Educational Resources Information Center

Gross, Jacob P. K.; Berry, Matthew S.

2016-01-01

To address conceptual and methodological shortcomings in the extant literature on student mobility, this study employs event history modeling to describe and explain how state policy levers, specifically state grant aid, relates to mobility and baccalaureate degree completion. We find that state grant aid reduces mobility, but less so than…

CALUTRONS

DOEpatents

Pierson, W.M.

1958-09-16

A vacuum tank is described for a calutron and the mounting means for the tank whereby the tank mav be convenlently positioned in the proper place between the poles of the magnet and there readily adjuated in height. A plurality of grooved guide wheels are mounted on adjustable levers attached to one side of the tank, along with a plurality of plain rollers mounted on adjuatable levers attached to the same side of the tank on the opposite edge. The grooved guide wheels and rollers cooperate with a guide track and runway, respectively, fer movement of the tank into and out of the magant gap, while the adjustable levers permit the accurate positioning of the tank between the magnet pole pieces.

78 FR 57047 - Airworthiness Directives; Eurocopter France Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-17

... (Eurocopter) Model AS350 and AS355 helicopters, to require inspecting for a crack in the control lever... casting of TGB casing assemblies, which may lead to cracking. A crack in the control lever attachment yokes could cause a loss of tail rotor pitch control, and consequently, loss of control of the...

Measuring How Muscles Function in Levers.

ERIC Educational Resources Information Center

DeMont, M. Edwin

1996-01-01

Presents an exercise that examines the lever systems that function in the chelae of the American lobster. Involves calculating the mechanical and distance advantages of the crusher and pincer chelae and estimating the actual forces generated by the contraction of the muscles and the magnitude of the forces transmitted around the fulcrum to the tip…

Improving Teaching Effectiveness: Implementation, Appendixes D and E. The Intensive Partnerships for Effective Teaching through 2013-2014

ERIC Educational Resources Information Center

Stecher, Brian M.; Garet, Michael S.; Hamilton, Laura S.; Steiner, Elizabeth D.; Robyn, Abby; Poirier, Jeffrey; Holtzman, Deborah; Fulbeck, Eleanor S.; Chambers, Jay; de los Reyes, Iliana Brodziak

2016-01-01

This document provides the final two appendixes for "Improving Teaching Effectiveness: Implementation. The Intensive Partnerships for Effective Teaching through 2013-2014" (ED580306). Appendix D provides detailed discussions of lever implementation for each site along with the detailed coded lever tables. Appendix E summarizes the…

46 CFR 56.20-9 - Valve construction.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...

46 CFR 56.20-9 - Valve construction.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...

46 CFR 56.20-9 - Valve construction.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...

46 CFR 56.20-9 - Valve construction.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...

46 CFR 58.25-70 - Steering-gear control systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... MACHINERY AND RELATED SYSTEMS Steering Gear § 58.25-70 Steering-gear control systems. (a) Each power-driven... arranged so that one operation of the switch's lever automatically supplies power to a complete system and its associated power unit or units. This switch must be— (1) Operated by one lever; (2) Arranged so...

46 CFR 58.25-70 - Steering-gear control systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... MACHINERY AND RELATED SYSTEMS Steering Gear § 58.25-70 Steering-gear control systems. (a) Each power-driven... arranged so that one operation of the switch's lever automatically supplies power to a complete system and its associated power unit or units. This switch must be— (1) Operated by one lever; (2) Arranged so...

Compactor for Space Toilet

NASA Technical Reports Server (NTRS)

Autrey, David (Inventor); Morrison, Terrell Lee (Inventor); Kaufman, Cory (Inventor)

2017-01-01

A toilet for use on a space vehicle has a toilet bowl having a storage canister at a remote end for receiving human waste. The compactor includes a cable connected to a lever which pulls the cable in a direction forcing the compactor into the storage canister to compact the captured waste when the lever is actuated.

29 CFR 1918.52 - Specific requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...

29 CFR 1918.52 - Specific requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...

29 CFR 1918.52 - Specific requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...

29 CFR 1918.52 - Specific requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...

29 CFR 1918.52 - Specific requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...

Motivational State and Reward Content Determine Choice Behavior under Risk in Mice

PubMed Central

Leblond, Mona; Fan, David; Brynildsen, Julia K.; Yin, Henry H.

2011-01-01

Risk is a ubiquitous feature of the environment for most organisms, who must often choose between a small and certain reward and a larger but less certain reward. To study choice behavior under risk in a genetically well characterized species, we trained mice (C57BL/6) on a discrete trial, concurrent-choice task in which they must choose between two levers. Pressing one lever (safe choice) is always followed by a small reward. Pressing the other lever (risky choice) is followed by a larger reward, but only on some of the trials. The overall payoff is the same on both levers. When mice were not food deprived, they were indifferent to risk, choosing both levers with equal probability regardless of the level of risk. In contrast, following food or water deprivation, mice earning 10% sucrose solution were risk-averse, though the addition of alcohol to the sucrose solution dose-dependently reduced risk aversion, even before the mice became intoxicated. Our results falsify the budget rule in optimal foraging theory often used to explain behavior under risk. Instead, they suggest that the overall demand or desired amount for a particular reward determines risk preference. Changes in motivational state or reward identity affect risk preference by changing demand. Any manipulation that increases the demand for a reward also increases risk aversion, by selectively increasing the frequency of safe choices without affecting frequency of risky choices. PMID:21966504

Preloaded latching device

NASA Technical Reports Server (NTRS)

Wesselski, Clarence J. (Inventor); Nagy, Kornel (Inventor)

1992-01-01

A latching device is disclosed which is lever operated sequentially to actuate a set of collet fingers to provide a radial expansion and to actuate a force mechanism to provide a compressive gripping force for attaching first and second devices to one another. The latching device includes a body member having elongated collet fingers which, in a deactuated condition, is insertable through bores on the first and second devices so that gripping terminal portions on the collet fingers are proximate to the end of the bore of the first device while a spring assembly on the body member is located proximate to the outer surface of a second device. A lever is rotatable through 90 deg to move a latching rod to sequentially actuate and expand collet fingers and to actuate the spring assembly by compressing it. During the first 30 deg of movement of the lever, the collet fingers are actuated by the latching rod to provide a radial expansion and during the last 60 deg of movement of the lever, the spring assembly acts as a force mechanism and is actuated to develop a compressive latching force on the devices. The latching rod and lever are connected by a camming mechanism. The amount of spring force in the spring assembly can be adjusted; the body member can be permanently attached by a telescoping assembly to one of the devices; and the structure can be used as a pulling device for removing annular bearings or the like from blind bores.

Individual differences in pavlovian autoshaping of lever pressing in rats predict stress-induced corticosterone release and mesolimbic levels of monoamines.

PubMed

Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D

2000-03-01

Pavlovian autoshaping CRs are directed and reflexive consummatory responses targeted at objects repeatedly paired with rewarding substances. To evaluate the hypothesis that autoshaping may provide an animal learning model of vulnerability to drug abuse, this study relates individual differences in lever-press autoshaping CR performance in rats to stress-induced corticosterone release and tissue monoamine levels in the mesolimbic dopamine tract. Long-Evans rats (n = 14) were given 20 sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of food US. Large between-subjects differences in lever-press autoshaping CR performance were observed, with group high CR frequency (n = 5) performing many more lever press CRs than group low CR frequency (n = 9). Tail-blood samples were obtained before and after the 20th autoshaping session, then 24 h later the rats were sacrificed and dissection yielded tissue samples of nucleus accumbens (NAC), prefrontal cortex (PFC), caudate putamen (CP), and ventral tegmental area (VTA). Serum levels of postsession corticosterone were elevated in group high CR frequency. HPLC revealed that group high CR frequency had higher tissue levels of dopamine and DOPAC in NAC, lower levels of DOPAC/DA turnover in CP, and lower levels of 5-HIAA and lower 5-HIAA/5-HT turnover in VTA. The neurochemical profile of rats that perform more autoshaping CRs share some features of vulnerability to drug abuse.

1.5 °C ? - Solutions for avoiding catastrophic climate change in this century

NASA Astrophysics Data System (ADS)

Xu, Y.

2017-12-01

The historic Paris Agreement calls for limiting global temperature rise to "well below 2 °C." Because of uncertainties in emission scenarios, climate, and carbon cycle feedback, we interpret the Paris Agreement in terms of three climate risk categories and bring in considerations of low-probability (5%) high impact (LPHI) warming in addition to the central (˜50% probability) value. The current risk category of dangerous warming is extended to more categories, which are defined by us here as follows: >1.5 °C as dangerous; >3 °C as catastrophic; and >5 °C as unknown, implying beyond catastrophic, including existential threats. With unchecked emissions, the central warming can reach the dangerous level within three decades, with the LPHI warming becoming catastrophic by 2050. We outline a three-lever strategy to limit the central warming below the dangerous level and the LPHI below the catastrophic level, both in the near term (<2050) and in the long term (2100): the carbon neutral (CN) lever to achieve zero net emissions of CO2, the super pollutant (SP) lever to mitigate short-lived climate pollutants, and the carbon extraction and sequestration (CES) lever to thin the atmospheric CO2 blanket. Pulling on both CN and SP levers and bending the emissions curve by 2020 can keep the central warming below dangerous levels. To limit the LPHI warming below dangerous levels, the CES lever must be pulled as well to extract as much as 1 trillion tons of CO2 before 2100 to both limit the preindustrial to 2100 cumulative net CO2 emissions to 2.2 trillion tons and bend the warming curve to a cooling trend. In addition to present the analysis above, I will also share (1) perspective on developed and developing world actions and interactions on climate solutions; (2) Prof V. Ramanathan's interactions with the Pontifical Academy of Sciences and other religious groups which are highly valuable to the interdisciplinary audience.

THE DIAGNOSTIC ACCURACY OF THE LEVER SIGN FOR DETECTING ANTERIOR CRUCIATE LIGAMENT INJURY

PubMed Central

Anderson, Amanda; Watson, Seth; Dimeff, Robert J.

2017-01-01

Background An alternative physical examination procedure for evaluating the integrity of the anterior cruciate ligament (ACL) has been proposed in the literature but has not been validated in a broad population of patients with a symptomatic complaint of knee pain for its diagnostic value. Purpose To investigate the diagnostic accuracy of the Lever Sign to detect ACL tears and compare the results to Lachman testing in both supine and prone positions. Study design Prospective, blinded, diagnostic accuracy study. Methods Sixty-two consecutive patients with a complaint of knee pain were independently evaluated for the status of the ACL's integrity with the Lever Sign and the Lachman test in a prone and supine by a blinded examiner before any other diagnostic assessments were completed. Results Twenty-four of the 60 patients included in the analysis had a torn ACL resulting in a prevalence of 40%. The sensitivity of the Lever Sign, prone, and supine Lachman tests were 38, 83, and 67 % respectively and the specificity was 72, 89, and 97% resulting in positive likelihood ratios of 1.4, 7.5, and 24 and negative likelihood ratios of 0.86, 0.19, and 0.34 respectively. The positive predictive values were 47, 83, and 94% and the negative predictive values were 63, 89, and 81% respectively. The diagnostic odds ratios were 1.6, 40, and 70 with a number needed to diagnose of 10.3, 1.4, and 1.6 respectively. Conclusions The results of this study suggest that Lever Sign, in isolation, does not accurately detect the status of the ACL. During the clinical examination, the Lever Sign should be used as an adjunct to the gold standard assessment technique of anterior tibial translation assessment as employed in the Lachman tests in either prone or supine position. Level of Evidence 2 PMID:29234557

Effects of autoshaping procedures on 3H-8-OH-DPAT-labeled 5-HT1a binding and 125I-LSD-labeled 5-HT2a binding in rat brain.

PubMed

Tomie, Arthur; Di Poce, Jason; Aguado, Allison; Janes, Amy; Benjamin, Daniel; Pohorecky, Larissa

2003-06-13

Effects of experience with Pavlovian autoshaping procedures on lever-press autoshaping conditioned response (CR) performance and 3H-8-OH-DPAT-labeled binding of 5-HT(1a) receptors as well as 125I-LSD-labeled binding of 5-HT(2a) receptors were evaluated in four groups of male Long-Evans hooded rats. Two groups of rats (Group Paired High CR and Group Paired Low CR) received Pavlovian autoshaping procedures wherein the presentation of a lever (conditioned stimulus, CS) was followed by the response-independent presentation of food (unconditioned stimulus, US). Rats in Group Paired High CR (n=12) showed more rapid CR acquisition and higher asymptotic levels of lever-press autoshaping CR performance relative to rats in Group Low CR (n=12). Group Omission (n=9) received autoshaping with an omission contingency, such that performing the lever-press autoshaping CR resulted in the cancellation the food US, while Group Random (n=9) received presentations of lever CS and food US randomly with respect to one another. Though Groups Omission and Random did not differ in lever-press autoshaping CR performance, Group Omission showed significantly lower levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in post-synaptic areas (frontal cortex, septum, caudate putamen), as well as significantly higher plasma corticosterone levels than Group Random. In addition, Group Random showed higher levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in pre-synaptic somatodendritic autoreceptors on dorsal raphe nucleus relative to each of the other three groups. Autoradiographic analysis of 125I-LSD-labeled 5-HT(2a) receptor binding revealed no significant differences between Groups Paired High CR and Paired Low CR or between Groups Omission and Random in any brain regions.

Development of Neurophysiological Procedures for the Detection of Organic Contaminants in Water.

DTIC Science & Technology

1978-05-24

Weinstein, Ph . D.r:V Curt Weinstein, M. A. UP~ 1978 ONSTAEEf Supported by far Publi©c re•IO OJ Ce bibu*@ Unlimited U. S. Army Medical Research and...rat’s tongue made contact with the fluid, a circuit was completed - which activated the lever for£EBS (when C waý the stimulus) or activated the...presentation of a loud noxious noise if he pressed incorrectly. All rats were successfully conditioned to Ldetect the contaminant with high levels of

The effects of anorexic drugs on free-fed rats responding under a second-order FI15-min (FR10:S) schedule for high incentive foods.

PubMed

Evenden, John; Ko, Tracey

2007-02-01

Many similarities exist between the overconsumption of food, which results in obesity, and drug addiction. The present study investigated the effects of anorectic drugs on responding maintained by high incentive, but nutritionally unnecessary, food reinforcers using an FI15(fixed-ratio 10:S) schedule of reinforcement, similar to that used in studies on the incentive properties of drugs of abuse. Rats were trained to respond on a lever to gain access to two high incentive foods--chocolate chip cookies and cheese. Under the FI15(FR10:S) schedule, every 10th response (fixed-ratio 10) delivered a tone and light conditioned stimulus. The first ratio completed 15 min after the start of the session produced the conditioned stimulus and opened a door to give access to a piece of cookie. After 5 min to consume the high incentive food, a second 15-min interval was started, terminating in access to a second reinforcer, cheese. Once trained, the rats were given free access to laboratory chow in the home cage. They continued to work for the high incentive foods for a period of over 1 year, showing a pattern of responding appropriate to an FI(fixed-ratio) schedule. Naloxone (1.0 mg/kg), fenfluramine (1 and 2 mg/kg), D-amphetamine (0.25 and 0.5 mg/kg), and rimonabant (3 mg/kg) significantly reduced responding, especially in the second interval. In contrast, complete removal of the high incentive food from the test procedure did not immediately reduce the rate of responding, tending to increase it in the second of the intervals. Apparently, the drugs did not reduce responding by reducing the experienced magnitude of the high incentive food, but more probably by reducing the animals' motivation.

Enhancement of Extinction Learning Attenuates Ethanol-Seeking Behavior and Alters Plasticity in the Prefrontal Cortex

PubMed Central

Trantham-Davidson, Heather; Kassab, Amanda S.; Glen, William B.; Olive, M. Foster; Chandler, L. Judson

2014-01-01

Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity. PMID:24872560

Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex.

PubMed

Gass, Justin T; Trantham-Davidson, Heather; Kassab, Amanda S; Glen, William B; Olive, M Foster; Chandler, L Judson

2014-05-28

Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity. Copyright © 2014 the authors 0270-6474/14/347562-13$15.00/0.

Place and contingency differential responses of monkey septal neurons during conditional place-object discrimination.

PubMed

Kita, T; Nishijo, H; Eifuku, S; Terasawa, K; Ono, T

1995-03-01

To elucidate spatial and cognitive function of the septal nuclei, neural activity was recorded from alert monkeys during performance of a place-dependent go/no-go (PGN) task. Response/reinforcement contingencies of given objects were conditional upon the location of a motorized, movable device (cab) containing a monkey in one of four places. The task was initiated by presentation of the outside view (place phase) followed by presentation of an object (object phase) selected from a total of four. A lever press was reinforced only if the correct object was seen in its corresponding place, and the same object was never reinforced in any of the other three places. Of 430 septal neurons recorded, the responses during the place phase in the four places were significantly different in 58 neurons. Responses of eight of these neurons were also place-differential during the object phase as well as the place phase. Furthermore, when the outside view was not presented before the object phase, differential responses in the object phase disappeared. Responses of 91 neurons in the object phase were differential in terms of go/no-go responses and reward availability. Of these 91 neurons, 72 were further tested on a place-independent asymmetrical go/no-go (AGN) task, which required no conditional discrimination. Forty-three neurons responded differentially only in the PGN task. It is thus concluded that this PGN-specific activity reflected conditional place-object relations. Of the remaining 29 neurons that responded differentially in both tasks, 21 were further tested by a place-independent symmetrical go/no-go task (no-go responses were also rewarded). Responses of 19 of these 21 neurons were related to the reward/nonreward contingency but not to the response contingency. The results suggest that septal nuclei are involved in integrating spatial information, conditional place-object relations, and reward/nonreward contingency.

Effect of GABA agonists and GABA-A receptor modulators on cocaine- and food-maintained responding and cocaine discrimination in rats.

PubMed

Barrett, Andrew C; Negus, S Stevens; Mello, Nancy K; Caine, S Barak

2005-11-01

Recent studies indicate that GABAergic ligands modulate abuse-related effects of cocaine. The goal of this study was to evaluate the effects of a mechanistically diverse group of GABAergic ligands on the discriminative stimulus and reinforcing effects of cocaine in rats. One group of rats was trained to discriminate 5.6 mg/kg cocaine from saline in a two-lever, food-reinforced, drug discrimination procedure. In two other groups, responding was maintained by cocaine (0-3.2 mg/kg/injection) or liquid food (0-100%) under a fixed ratio 5 schedule. Six GABA agonists were tested: the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, the GABA transaminase inhibitor gamma-vinyl-GABA (GVG), and three GABA-A receptor modulators (the barbiturate pentobarbital, the high-efficacy benzodiazepine midazolam, and the low-efficacy benzodiazepine enazenil). When tested alone, none of the compounds substituted fully for the discriminative stimulus effects of cocaine. As acute pretreatments, select doses of midazolam and pentobarbital produced 2.2- to 3.6-fold rightward shifts in the cocaine dose-effect function. In contrast, muscimol, baclofen, GVG, and enazenil failed to alter the discriminative stimulus effects of cocaine. In assays of cocaine- and food-maintained responding, midazolam and pentobarbital decreased cocaine self-administration at doses 9.6- and 3.3-fold lower, respectively, than those that decreased food-maintained responding. In contrast, muscimol, baclofen, and GVG decreased cocaine self-administration at doses that also decreased food-maintained responding. Enazenil failed to alter cocaine self-administration. Together with previous studies, these data suggest that among mechanistically diverse GABA agonists, high-efficacy GABA-A modulators may be the most effective for modifying the abuse-related effects of cocaine.

Effects of dopamine D1 receptor blockade in the prelimbic prefrontal cortex or lateral dorsal striatum on frontostriatal function in Wistar and Spontaneously Hypertensive Rats.

PubMed

Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P; Kantak, Kathleen M

2014-07-15

Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0 μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

JPRS Report, China.

DTIC Science & Technology

1991-12-03

BANKING Hidden Financial Distribution [CAIMAO JINGJI No8] .................................... .. . .. .. 25 Guangxi Tax Chief on Using Tax Levers [GUANGXI...assets is confused. economy. They are of major importance in the invigo- Under the financial contracting system, the conflict ration of large and...to various economic levers and legal strictures state, and to change enterprises from appendages of the such as financial , fiscal, and tax policies

Observing Responses and Serial Stimuli: Searching for the Reinforcing Properties of the S-

ERIC Educational Resources Information Center

Escobar, Rogelio; Bruner, Carlos A.

2009-01-01

The control exerted by a stimulus associated with an extinction component (S-) on observing responses was determined as a function of its temporal relation with the onset of the reinforcement component (S+). Lever pressing by rats was reinforced on a mixed random-interval extinction schedule. Each press on a second lever produced stimuli…

Cognitive Effects on the Child's Internalization of Altruistic Behavior.

ERIC Educational Resources Information Center

Baxter, George W.

Cognitive effects in children's learning of altruistic behavior were tested with an adaptation of Aronfreed's test design and machine. Children in grades 1-4 were presented with a machine with 2 levers. One lever, when pressed, released bubble gum, and the other turned on a light. For two of the three groups the experimenter exclaimed delightedly…

75 FR 27403 - Airworthiness Directives; Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model EMB-135 and -145...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

... commanding the landing gear lever to down the three green landing gear positioning indication was displayed... unsafe condition for the specified products. The MCAI states: It was reported that after commanding the...: It was reported that after commanding the landing gear lever to down the three green landing gear...

Responding for sucrose and wheel-running reinforcement: effects of sucrose concentration and wheel-running reinforcer duration.

PubMed

Belke, Terry W; Hancock, Stephanie D

2003-03-01

Six male albino rats were placed in running wheels and exposed to a fixed-interval 30-s schedule of lever pressing that produced either a drop of sucrose solution or the opportunity to run for a fixed duration as reinforcers. Each reinforcer type was signaled by a different stimulus. In Experiment 1, the duration of running was held constant at 15 s while the concentration of sucrose solution was varied across values of 0, 2.5. 5, 10, and 15%. As concentration decreased, postreinforcement pause duration increased and local rates decreased in the presence of the stimulus signaling sucrose. Consequently, the difference between responding in the presence of stimuli signaling wheel-running and sucrose reinforcers diminished, and at 2.5%, response functions for the two reinforcers were similar. In Experiment 2, the concentration of sucrose solution was held constant at 15% while the duration of the opportunity to run was first varied across values of 15, 45, and 90 s then subsequently across values of 5, 10, and 15 s. As run duration increased, postreinforcement pause duration in the presence of the wheel-running stimulus increased and local rates increased then decreased. In summary, inhibitory aftereffects of previous reinforcers occurred when both sucrose concentration and run duration varied; changes in responding were attributable to changes in the excitatory value of the stimuli signaling the two reinforcers.

Cue dependency of nicotine self-administration and smoking.

PubMed

Caggiula, A R; Donny, E C; White, A R; Chaudhri, N; Booth, S; Gharib, M A; Hoffman, A; Perkins, K A; Sved, A F

2001-12-01

A paradox exists regarding the reinforcing properties of nicotine. The abuse liability associated with smoking equals or exceeds that of other addictive drugs, yet the euphoric, reinforcing and other psychological effects of nicotine, compared to these other drugs, are more subtle, are manifest under more restricted conditions, and do not readily predict the difficulty most smokers experience in achieving abstinence. One possible resolution to this apparent inconsistency is that environmental cues associated with drug delivery become conditioned reinforcers and take on powerful incentive properties that are critically important for sustaining smoking in humans and nicotine self-administration in animals. We tested this hypothesis by using a widely employed self-administration paradigm in which rats press a lever at high rates for 1 h/day to obtain intravenous infusions of nicotine that are paired with two types of visual stimuli: a chamber light that when turned on signals drug availability and a 1-s cue light that signals drug delivery. We show that these visual cues are at least as important as nicotine in sustaining a high rate of responding once self-administration has been established, in the degree to which withdrawing nicotine extinguishes the behavior, and in the reinstatement of lever pressing after extinction. Additional studies demonstrated that the importance of these cues was manifest under both fixed ratio and progressive ratio (PR) schedules of reinforcement. The possibility that nicotine-paired cues are as important as nicotine in smoking behavior should refocus our attention on the psychology and neurobiology of conditioned reinforcers in order to stimulate the development of more effective treatment programs for smoking cessation.

Methamphetamine, d-amphetamine and p-chloroamphetamine induced neurotoxicity differentially effect impulsive responding on the stop-signal task in rats

PubMed Central

Furlong, Teri M.; Leavitt, Lee S.; Keefe, Kristen A.; Son, Jong-Hyun

2016-01-01

Abused amphetamines, such as d-amphetamine (AMPH) and methamphetamine (METH), are highly addictive and destructive to health and productive lifestyles. The abuse of these drugs is associated with impulsive behavior, which is likely to contribute to addiction. The amphetamines also differentially damage dopamine (DA) and serotonin (5-HT) systems, which regulate impulsive behavior; therefore, exposure to these drugs may differentially alter impulsive behavior to effect the progression of addiction. We examined the impact of neurotoxicity induced by three amphetamines on impulsive action using a stop-signal task in rats. Animals were rewarded with a food pellet after lever pressing (i.e. a go trial), unless an auditory cue was presented and withholding lever press gained reward (i.e. a stop trial). Animals were trained on the task and then exposed to a neurotoxic regimen of either AMPH, p-chloroamphetamine (PCA), or METH. These regimens preferentially reduced DA transporter levels in striatum, 5-HT transporter levels in prefrontal cortex, or both, respectively. Assessment of performance on the stop-signal task beginning one week after the treatment revealed that AMPH produced a deficit in go-trial performance, whereas PCA did not alter performance on either trial type. In contrast, METH produced a deficit in stop-trial performance (i.e. impulsive action) but not go-trial performance. These findings suggest that the different neurotoxic consequences of substituted amphetamines are associated with different effects on inhibitory control over behavior. Thus, the course of addiction and maladaptive behavior resulting from exposure to these substances is likely to differ. PMID:26846719

Assessing Social Cognition: A New Instrumental Paradigm Based on Contingent Feedback

ERIC Educational Resources Information Center

Bertin, Evelin; Wong, Charlene; Striano, Tricia

2016-01-01

Seven- to 12-month-olds were trained to press levers that contingently activated lights. Infants had the choice of turning on either a light an adult interaction partner was looking at or a light that she turned away from. By 9 months, infants reliably turned on the light that the adult was looking at. In a second study, 9- and 12-month-old…

Effects of menthol and its interaction with nicotine-conditioned cue on nicotine-seeking behavior in rats.

PubMed

Harrison, Erin; Biswas, Lisa; Avusula, Ramachandram; Zhang, Meiyu; Gong, Yongzhen; Liu, Xiu

2017-12-01

Increasing clinical evidence suggests that menthol, a significant flavoring additive in tobacco products, may contribute to smoking and nicotine dependence. Relapse to smoking behavior presents a formidable challenge for the treatment of tobacco addiction. An unresolved issue is whether the mentholation of tobacco products precipitates relapse to tobacco use in abstinent smokers. The present study examined the effects of menthol on the perseverance and relapse of nicotine-seeking behavior in rats. Male Sprague-Dawley rats were trained to press a lever for intravenous nicotine self-administration (0.03 mg/kg/infusion) under a fixed-ratio five schedule of reinforcement. Each nicotine infusion was signaled by the presentation of a sensory stimulus that was established as a discrete nicotine-conditioned cue. Five minutes prior to the sessions, the rats received an intraperitoneal injection of menthol (0.1 mg/kg) or vehicle. In the subsequent extinction test sessions, nicotine was unavailable with or without menthol and/or the nicotine-conditioned cue. The reinstatement tests were performed the following day after the extinction criterion was met. Menthol was also tested on food-seeking responses. In a subset of nicotine-trained rats, a transient receptor potential melastatin 8 (TRPM8) antagonist RQ-00203078 was given prior to menthol administration. Continued administration of menthol sustained responses on the previously active and nicotine-reinforced lever in the extinction tests. The readministration of menthol after extinction reinstated active lever responses. In both the extinction and the reinstatement tests, a combination of pre-session menthol administration and cue representation during the session produced a more robust behavioral effect than either menthol or the cue alone. No such effects of menthol was observed in food trained rats. RQ-00203078 did not change menthol effect on nicotine seeking. These data demonstrated that menthol specifically sustained and reinstated nicotine-seeking behavior, and this effect was independent of TRPM8 activity. These findings suggest that menthol in most tobacco products, even not menthol labeled, may contribute to the perseverance of and relapse to tobacco-seeking behavior.

Blockade of mesolimbic dopamine D3 receptors inhibits stress-induced reinstatement of cocaine-seeking in rats

PubMed Central

Gilbert, Jeremy; Campos, Arlene C.; Kline, Nicole; Ashby, Charles R.; Hagan, Jim J.; Heidbreder, Christian A.; Gardner, Eliot L.

2013-01-01

Rationale The dopamine (DA) D3 receptor is preferentially expressed in the mesolimbic system. We have previously shown that selective D3 receptor blockade by the novel D3 antagonist SB-277011A inhibits cocaine’s reinforcing action and cocaine-induced reinstatement of cocaine-seeking behavior. Objective In the present study, we investigated whether SB-277011A similarly inhibits stress-induced reinstatement of cocaine-seeking behavior. Methods Rats were allowed to self-administer cocaine (0.5 mg/kg per infusion, 3 h per session) for 10–14 days, followed by a once-daily extinction session for 7–14 days during which saline was substituted for cocaine. Extinction criteria were fewer than ten lever-presses per 3-h session for at least 3 consecutive days. After cocaine-seeking behavior was extinguished, each animal was tested twice for footshock-stress-induced reinstatement, once with vehicle (25% hydroxypropyl-β-cyclodextrin) and once with one of three doses of SB-277011A in counterbalanced fashion. Results During the last 3 days of cocaine self-administration (SA), active lever-presses were approximately 100 per session under fixed-ratio 2 reinforcement (~25 mg/kg cocaine per session). After extinction, intermittent footshock (10 min, 0.5 mA, 0.5 s on with a mean inter-shock interval of 40 s) robustly reinstated the cocaine-seeking behavior (8.4±3.6 active lever-presses in last extinction session to 35.3±5.2 in animals after footshock stress). Intraperitoneal (IP) injections of SB-277011A (3, 6, and 12 mg/kg) dose-dependently blocked stress-induced reinstatement of cocaine-seeking. Reinstatement was also blocked by microinjections of SB-277011A (1.5 μg/0.5 μl per side) bilaterally into the nucleus accumbens, but not into the dorsal striatum. Conclusions The mesolimic DA D3 receptor plays an important role in mediating stress-induced reinstatement. PMID:15083257

Behavioral regulation of gravity - Schedule effects under escape-avoidance procedures

NASA Technical Reports Server (NTRS)

Clark, F. C.; Lange, K. O.; Belleville, R. E.

1973-01-01

Squirrel monkeys were restrained in a centrifuge capsule and trained to escape and avoid increases in artificial gravity. During escape-avoidance, lever responses reduced centrifugally simulated gravity or postponed scheduled increases. The effect of variation in the interval of postponement (equal to the duration of decrease produced by escape responses) was studied under a multiple schedule of four components. Three components were gravity escape-avoidance with postponement times of 20, 40, and 60 sec. The fourth component was extinction. Each component was associated with a different auditory stimulus. Rate of responding decreased with increasing postponement time and higher mean g-levels occurred at shorter intervals of postponement. Effects of the schedule parameter on response rate and mean g-level were similar to effects of the schedule on free-operant avoidance and on titration behavior maintained by shock.

Small step tracking - Implications for the oculomotor 'dead zone'. [eye response failure below threshold target displacements

NASA Technical Reports Server (NTRS)

Wyman, D.; Steinman, R. M.

1973-01-01

Recently Timberlake, Wyman, Skavenski, and Steinman (1972) concluded in a study of the oculomotor error signal in the fovea that 'the oculomotor dead zone is surely smaller than 10 min and may even be less than 5 min (smaller than the 0.25 to 0.5 deg dead zone reported by Rashbass (1961) with similar stimulus conditions).' The Timberlake et al. speculation is confirmed by demonstrating that the fixating eye consistently and accurately corrects target displacements as small as 3.4 min. The contact lens optical lever technique was used to study the manner in which the oculomotor system responds to small step displacements of the fixation target. Subjects did, without prior practice, use saccades to correct step displacements of the fixation target just as they correct small position errors during maintained fixation.

Event-related oscillations (ERO) during an active discrimination task: Effects of lesions of the Nucleus Basalis Magnocellularis

PubMed Central

Sanchez-Alavez, Manuel; Ehlers, Cindy L.

2015-01-01

The cholinergic system in the brain is involved in attentional processes that are engaged for the identification and selection of relevant information in the environment and the formation of new stimulus associations. In the present study we determined the effects of cholinergic lesions of nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs) generated in an auditory active discrimination task in rats. Rats were trained to press a lever to begin a series of 1K Hz tones and to release the lever upon hearing a 2 kHz tone. A time-frequency based representation was used to determine ERO energy and phase synchronization (phase lock index, PLI) across trials, recorded within frontal cortical structures. Lesions in NBM produced by an infusion of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) resulted in (1) a reduction of the number of correct behavioral responses in the active discrimination task, (2) an increase in ERO energy in the delta frequency bands (3) an increase in theta, alpha and beta ERO energy in the N1, P3a and P3b regions of interest (ROI), and (4) an increase in PLI in the theta frequency band in the N1 ROIs. These studies suggest that the NBM cholinergic system is involved in maintaining the synchronization/phase resetting of oscillations in different frequencies in response to the presentation of the target stimuli in an active discrimination task. PMID:25660307

Resurgence and alternative-reinforcer magnitude.

PubMed

Craig, Andrew R; Browning, Kaitlyn O; Nall, Rusty W; Marshall, Ciara M; Shahan, Timothy A

2017-03-01

Resurgence is defined as an increase in the frequency of a previously reinforced target response when an alternative source of reinforcement is suspended. Despite an extensive body of research examining factors that affect resurgence, the effects of alternative-reinforcer magnitude have not been examined. Thus, the present experiments aimed to fill this gap in the literature. In Experiment 1, rats pressed levers for single-pellet reinforcers during Phase 1. In Phase 2, target-lever pressing was extinguished, and alternative-lever pressing produced either five-pellet, one-pellet, or no alternative reinforcement. In Phase 3, alternative reinforcement was suspended to test for resurgence. Five-pellet alternative reinforcement produced faster elimination and greater resurgence of target-lever pressing than one-pellet alternative reinforcement. In Experiment 2, effects of decreasing alternative-reinforcer magnitude on resurgence were examined. Rats pressed levers and pulled chains for six-pellet reinforcers during Phases 1 and 2, respectively. In Phase 3, alternative reinforcement was decreased to three pellets for one group, one pellet for a second group, and suspended altogether for a third group. Shifting from six-pellet to one-pellet alternative reinforcement produced as much resurgence as suspending alternative reinforcement altogether, while shifting from six pellets to three pellets did not produce resurgence. These results suggest that alternative-reinforcer magnitude has effects on elimination and resurgence of target behavior that are similar to those of alternative-reinforcer rate. Thus, both suppression of target behavior during alternative reinforcement and resurgence when conditions of alternative reinforcement are altered may be related to variables that affect the value of the alternative-reinforcement source. © 2017 Society for the Experimental Analysis of Behavior.

Resurgence and Alternative-Reinforcer Magnitude

PubMed Central

Craig, Andrew R.; Browning, Kaitlyn O.; Nall, Rusty W.; Marshall, Ciara M.; Shahan, Timothy A.

2017-01-01

Resurgence is defined as an increase in the frequency of a previously reinforced target response when an alternative source of reinforcement is suspended. Despite an extensive body of research examining factors that affect resurgence, the effects of alternative-reinforcer magnitude have not been examined. Thus, the present experiments aimed to fill this gap in the literature. In Experiment 1, rats pressed levers for single-pellet reinforcers during Phase 1. In Phase 2, target-lever pressing was extinguished, and alternative-lever pressing produced either five-pellet, one-pellet, or no alternative reinforcement. In Phase 3, alternative reinforcement was suspended to test for resurgence. Five-pellet alternative reinforcement produced faster elimination and greater resurgence of target-lever pressing than one-pellet alternative reinforcement. In Experiment 2, effects of decreasing alternative-reinforcer magnitude on resurgence were examined. Rats pressed levers and pulled chains for six-pellet reinforcers during Phases 1 and 2, respectively. In Phase 3, alternative reinforcement was decreased to three pellets for one group, one pellet for a second group, and suspended altogether for a third group. Shifting from six-pellet to one-pellet alternative reinforcement produced as much resurgence as suspending alternative reinforcement altogether, while shifting from six pellets to three pellets did not produce resurgence. These results suggest that alternative-reinforcer magnitude has effects on elimination and resurgence of target behavior that are similar to those of alternative-reinforcer rate. Thus, both suppression of target behavior during alternative reinforcement and resurgence when conditions of alternative reinforcement are altered may be related to variables that affect the value of the alternative-reinforcement source. PMID:28194793

Enhanced performance of aged rats in contingency degradation and instrumental extinction tasks.

PubMed

Samson, Rachel D; Venkatesh, Anu; Patel, Dhara H; Lipa, Peter; Barnes, Carol A

2014-04-01

Normal aging in rats affects behavioral performance on a variety of associative learning tasks under Pavlovian conditions. There is little information, however, on whether aging also impacts performance of instrumental tasks. Young (9-12 months) and aged (24-27 months) Fisher 344 rats were trained to press distinct levers associated with either maltodextrin or sucrose. The rats in both age groups increased their lever press frequency at a similar rate, suggesting that the initial acquisition of this instrumental task is not affected by aging. Using a contingency degradation procedure, we then addressed whether aged rats could adapt their behavior to changes in action-outcome contingencies. We found that young and aged rats do adapt, but that a different schedule of reinforcement is necessary to optimize performance in each age group. Finally, we also addressed whether aged rats can extinguish a lever press action as well as young rats, using 2 40-min extinction sessions on consecutive days. While extinction profiles were similar in young and aged rats on the first day of training, aged rats were faster to extinguish their lever presses on the second day, in spite of their performance levels being similar at the beginning of the session. Together these data support the finding that acquisition of instrumental lever press behaviors is preserved in aged rats and suggest that they have a different threshold for switching strategies in response to changes in action-outcome associations. This pattern of result implies that age-related changes in the brain are heterogeneous and widespread across structures.

Evaluation of Physical Examination Tests for Thumb Basal Joint Osteoarthritis

PubMed Central

Model, Zina; Liu, Andrew Y.; Kang, Lana; Wolfe, Scott W.; Burket, Jayme C.; Lee, Steve K.

2016-01-01

Background: We compare the ability of 3 diagnostic tests to reproduce the pain of basilar joint arthritis (BJA): the grind test, the lever test (grasping the first metacarpal just distal to the basal joint and shucking back and forth in radial and ulnar directions), and the metacarpophalangeal extension test. Methods: Sixty-two patients with thumb BJA were enrolled. The 3 tests were performed in a random order on both hands of each patient. Prior to testing, patients reported their typical pain level and subsequently rated their pain after each test on a 0 to 10 scale, also specifying the extent to which the test reproduced their thumb pain (fully, partially, not at all). All patients had radiographs that displayed basal joint arthritis. A test was defined as positive for BJA if pain produced was greater than 0. Sensitivity and specificity for each test were calculated using the patients’ history of pain localized to the basal joint and BJA diagnosis on radiographs as the gold standard. Results: The lever test produced the greatest level of pain and best reproduced the presenting pain. The lever test also had the highest sensitivity, high specificity, and the lowest false-negative rate. The grind test had the lowest sensitivity, highest specificity, and highest false-negative rate. Conclusions: The lever test was the diagnostic test that best reproduced the pain caused by thumb basal joint osteoarthritis. We recommend using the lever physical examination test when evaluating the patient with suspected basal joint osteoarthritis. The often-quoted grind test is of limited diagnostic value. PMID:27418899

Amphetamine primes enhanced motivation toward uncertain choices in rats with genetic alcohol preference.

PubMed

Oinio, Ville; Sundström, Mikko; Bäckström, Pia; Uhari-Väänänen, Johanna; Kiianmaa, Kalervo; Raasmaja, Atso; Piepponen, Petteri

2018-05-01

Comorbidity with gambling disorder (GD) and alcohol use disorder (AUD) is well documented. The purpose of our study was to examine the influence of genetic alcohol drinking tendency on reward-guided decision making behavior of rats and the impact of dopamine releaser D-amphetamine on this behavior. In this study, Alko alcohol (AA) and Wistar rats went through long periods of operant lever pressing training where the task was to choose the profitable of two options. The lever choices were guided by different-sized sucrose rewards (one or three pellets), and the probability of gaining the larger reward was slowly changed to a level where choosing the smaller reward would be the most profitable in the long run. After training, rats were injected (s.c.) with dopamine releaser D-amphetamine (0.3, 1.0 mg/kg) to study the impact of rapid dopamine release on this learned decision making behavior. Administration of D-amphetamine promoted unprofitable decision making of AA rats more robustly when compared to Wistar rats. At the same time, D-amphetamine reduced lever pressing responses. Interestingly, we found that this reduction in lever pressing was significantly greater in Wistar rats than in AA rats and it was not linked to motivation to consume sucrose. Our results indicate that conditioning to the lever pressing in uncertain environments is more pronounced in AA than in Wistar rats and indicate that the reinforcing effects of a gambling-like environment act as a stronger conditioning factor for rats that exhibit a genetic tendency for high alcohol drinking.

Enhanced performance of aged rats in contingency degradation and instrumental extinction tasks

PubMed Central

Samson, Rachel D.; Venkatesh, Anu; Patel, Dhara H.; Lipa, Peter; Barnes, Carol A.

2014-01-01

Normal aging in rats affects behavioral performance on a variety of associative learning tasks under Pavlovian conditions. There is little information, however, on whether aging also impacts performance of instrumental tasks. Young (9–12 mo) and aged (24–27 mo) Fisher 344 rats were trained to press distinct levers associated with either maltodextrin or sucrose. The rats in both age groups increased their lever press frequency at a similar rate, suggesting that the initial acquisition of this instrumental task is not affected by aging. Using a contingency degradation procedure, we then addressed whether aged rats could adapt their behavior to changes in action-outcome contingencies. We found that young and aged rats do adapt, but that a different schedule of reinforcement is necessary to optimize performance in each age group. Finally, we also addressed whether aged rats can extinguish a lever press action as well as young rats, using two forty minute extinction sessions on consecutive days. While extinction profiles were similar in young and aged rats on the first day of training, aged rats were faster to extinguish their lever presses on the second day, in spite of their performance levels being similar at the beginning of the session. Together these data support the finding that acquisition of instrumental lever press behaviors is preserved in aged rats, and suggest that they have a different threshold for switching strategies in response to changes in action-outcome associations. This pattern of result implies that age-related changes in the brain are heterogeneous and widespread across structures. PMID:24773433

The HIV antiretroviral drug efavirenz has LSD-like properties.

PubMed

Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C; France, Charles P; Dillon, Glenn H; Forster, Michael J; Schetz, John A

2013-11-01

Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, interaction with the 5-HT(2A) receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT(2A) receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT(2A)-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT(2A) receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication.

The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties

PubMed Central

Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C; France, Charles P; Dillon, Glenn H; Forster, Michael J; Schetz, John A

2013-01-01

Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT2A receptors. In rodents, interaction with the 5-HT2A receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT2A receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT2A-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT2A receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication. PMID:23702798

Cocaine hydrolase encoded in viral vector blocks the reinstatement of cocaine seeking in rats for 6 months

PubMed Central

Anker, Justin J.; Brimijoin, Stephen; Gao, Yang; Geng, Liyi; Zlebnik, Natalie E.; Parks, Robin J.; Carroll, Marilyn E.

2011-01-01

Background Cocaine dependence is a pervasive disorder with high rates of relapse. In a previous study, direct administration of a quadruple mutant albumin-fused butyrylcholinesterase (BChE) that efficiently catalyzes hydrolysis of cocaine to benzoic acid and ecgonine methyl ester acutely blocked cocaine seeking in an animal model of relapse. In the present experiments these results were extended to achieve a long duration blockade of cocaine seeking with a gene transfer paradigm using a related BChE-based cocaine hydrolase, termed “CocH”. Methods Male and female rats were allowed to self-administer cocaine under a fixed-ratio 1 schedule of reinforcement for approximately 14 days. Following the final self-administration session, rats were injected with CocH vector or a control injection (empty vector or saline), and their cocaine solutions were replaced with saline for 14 days to allow for extinction of lever pressing. Subsequently, they were tested for drug-primed reinstatement by administering i.p. injections of saline (S), cocaine (5, 10, and 15 mg/kg, C), and d-amphetamine (A) according to the following sequence: S, C, S, C, S, C, S, A. Rats then received cocaine-priming injections once weekly for 4 weeks, and subsequently, once monthly for up to 6 months. Results Administration of CocH vector produced substantial and sustained CocH activity in plasma that corresponded with diminished cocaine- (but not amphetamine-) induced reinstatement responding for up to 6 months following treatment (compared to high responding controls). Conclusion These results demonstrate that viral transfer of CocH may be useful in promoting long-term resistance to relapse to cocaine addiction. PMID:22209637

METHAMPHETAMINE-INDUCED DOPAMINE TERMINAL DEFICITS IN THE NUCLEUS ACCUMBENS ARE EXACERBATED BY REWARD-ASSOCIATED CUES AND ATTENUATED BY CB1 RECEPTOR ANTAGONISM

PubMed Central

Loewinger, Gabriel C.; Beckert, Michael V.; Tejeda, Hugo A.; Cheer, Joseph F.

2012-01-01

Methamphetamine (METH) exposure is primarily associated with deleterious effects to dopaminergic neurons. While several studies have implicated the endocannabinoid system in METH’s locomotor, rewarding and neurochemical effects, a role for this signaling system in METH’s effects on dopamine terminal dynamics has not been elucidated. Given that CB1 receptor blockade reduces the acute potentiation of phasic extracellular dopamine release from other psychomotor stimulant drugs and that the degree of acute METH-induced increases in extracellular dopamine levels is related to the severity of dopamine depletion, we predicted that pretreatment with the CB1 receptor antagonist rimonabant would reduce METH-induced alterations at dopamine terminals. Furthermore, we hypothesized that administration of METH in environments where reward associated-cues were present would potentiate METH’s acute effects on dopamine release in the nucleus accumbens and exacerbate changes in dopamine terminal activity. Fast-scan cyclic voltammetry was used to measure electrically-evoked dopamine release in the nucleus accumbens and revealed markers of compromised dopamine terminal integrity nine days after a single dose of METH. These were exacerbated in animals that received METH in the presence of reward-associated cues, and attenuated in rimonabant-pretreated animals. While these deficits in dopamine dynamics were associated with reduced operant responding on days following METH administration in animals treated with only METH, rimonabant-pretreated animals exhibited levels of operant responding comparable to control. Moreover, dopamine release correlated significantly with changes in lever pressing behavior that occurred on days following METH administration. Together these data suggest that the endocannabinoid system is involved in the subsecond dopaminergic response to METH. PMID:22306525

Applying a typology of health worker migration to non-EU migrant doctors in Ireland.

PubMed

Humphries, Niamh; McAleese, Sara; Tyrrell, Ella; Thomas, Steve; Normand, Charles; Brugha, Ruairí

2015-06-26

Research on health worker migration in the Irish context has categorized migrant health workers by country or region of training (for example, non-EU nurses or doctors) or recruitment mechanism (for example, actively recruited nurses). This paper applies a new typology of health worker migrants - livelihood, career-oriented, backpacker, commuter, undocumented and returner migrants (European Observatory on Health Systems and Policies and WHO, vol. 2:129-152, 2014) - to the experiences of non-EU migrant doctors in Ireland and tests its utility for understanding health worker migration internationally. The paper draws on quantitative survey (N = 366) and qualitative interview (N = 37) data collected from non-EU migrant doctors in Ireland between 2011 and 2013. Categorizing non-EU migrant doctors in Ireland according to the typology (European Observatory on Health Systems and Policies and WHO, vol. 2:129-152, 2014) offers insight into their differing motivations, particularly on arrival. Findings suggest that the career-oriented migrant is the most common type of doctor among non-EU migrant doctor respondents, accounting for 60 % (N = 220) of quantitative and 54 % (N = 20) of qualitative respondents. The authors propose a modification to the typology via the addition of two additional categories - the family migrant and the safety and security migrant. Employing a typology of health worker migration can facilitate a more comprehensive understanding of the migrant medical workforce, a necessary prerequisite for the development of useful policy tools (European Observatory on Health Systems and Policies and WHO, vol. 2:129-152, 2014). The findings indicate that there is some fluidity between categories, as health worker motivations change over time. This indicates the potential for policy levers to influence migrant health worker decision-making, if they are sufficiently "tuned in" to migrant health worker motivation.

Differential effects of MPEP and diazepam in tests of conditioned emotional response and Pavlovian-to-instrumental transfer suggests 'anxiolytic' effects are mediated by different mechanisms.

PubMed

George, S A; Hutson, P H; Stephens, D N

2009-06-01

The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is reported to be anxiolytic in several animal models of anxiety, including the conditioned emotional response (CER) paradigm. Suppression of responding during conditioned stimulus (CS) presentation in CER may reflect behavioural competition between lever pressing and adopting a shock-avoidance posture, or it may alternatively reflect altered value of the food reward following its association with a footshock, thus reducing its ability to motivate responding. If this is the case, then drugs that reduce the CER may interfere with the mechanism by which CSs are able to motivate responding, rather than by reducing anxiety. The standard test of the ability of Pavlovian cues to motivate responding is the Pavlovian-to-instrumental transfer (PIT) paradigm and it has recently been suggested that CER may be 'negative PIT'. We compared the effect of MPEP (0, 3, 10 and 30 mg/kg) and diazepam (0, 1, 3 and 10 mg/kg) in CER and PIT. Both MPEP and diazepam significantly reduced conditioned suppression in the CER paradigm. MPEP, but not diazepam, significantly reduced PIT. The findings support the hypothesis that MPEP may reduce expression of anxiety in the CER paradigm by interfering with the way in which emotionally salient cues are able to affect behaviour, but do not support such an analysis of the effect of diazepam. Diazepam and MPEP may therefore achieve their effects in CER by influencing different psychological processes.

Rats that sign-track are resistant to Pavlovian but not instrumental extinction

PubMed Central

Ahrens, Allison M.; Singer, Bryan F.; Fitzpatrick, Christopher J.; Morrow, Jonathan D.; Robinson, Terry E.

2015-01-01

Individuals vary in the extent to which they attribute incentive salience to a discrete cue (conditioned stimulus; CS) that predicts reward delivery (unconditioned stimulus; US), which results in some individuals approaching and interacting with the CS (sign-trackers; STs) more than others (goal-trackers; GTs). Here we asked how periods of non-reinforcement influence conditioned responding in STs vs. GTs, in both Pavlovian and instrumental tasks. After classifying rats as STs or GTs by pairing a retractable lever (the CS) with the delivery of a food pellet (US), we introduced periods of non-reinforcement, first by simply withholding the US (i.e., extinction training; experiment 1), then by signaling alternating periods of reward (R) and non-reward (NR) within the same session (experiments 2 and 3). We also examined how alternating R and NR periods influenced instrumental responding for food (experiment 4). STs and GTs did not differ in their ability to discriminate between R and NR periods in the instrumental task. However, in Pavlovian settings STs and GTs responded to periods of non-reward very differently. Relative to STs, GTs very rapidly modified their behavior in response to periods of non-reward, showing much faster extinction and better and faster discrimination between R and NR conditions. These results highlight differences between Pavlovian and instrumental extinction learning, and suggest that if a Pavlovian CS is strongly attributed with incentive salience, as in STs, it may continue to bias attention toward it, and to facilitate persistent and relatively inflexible responding, even when it is no longer followed by reward. PMID:26235331

Contrasting Effects of Lithium Chloride and CB1 Receptor Blockade on Enduring Changes in the Valuation of Reward.

PubMed

Hernandez, Giovanni; Bernstein, David; Schoenbaum, Geoffrey; Cheer, Joseph F

2011-01-01

When an organism responds for a reward, its learned behavior can be characterized as goal-directed or habitual based on whether or not it is susceptible to reward devaluation. Here, we evaluated whether instrumental responding for brain stimulation reward (BSR) can be devalued using a paradigm traditionally used for natural rewards. Rats were trained to lever press for BSR; afterward, BSR was paired with either lithium chloride (LiCl, 5 mg/kg, i.p.), a pro-emetic, or AM251, a CB1 receptor antagonist (3 mg/kg, i.p.) or the vehicle of these compounds. Pairings of BSR with these compounds and their vehicles were performed in a novel environment so that only unconditional effects of BSR would be affected by the pharmacological manipulations. Subsequently, in a probe test, all rats were returned in the drug-free state to the boxes where they had received training and instrumental responding was reassessed in the absence of BSR delivery. When compared to control, LiCl produced a significant decrease in the number of responses during the test session, whereas AM251 did not. These results show that instrumental responding for BSR is susceptible to devaluation, in accord with the proposal that this behavior is supported at least in part by associations between the response and the rewarding outcome. Further, they suggest that reward modulation observed in studies involving the use of CB1 receptor antagonists arises from changes in the organism's motivation rather than drug-induced changes in the intrinsic value of reward.

Increased behavioral output but intact goal-directed and habitual responding for food reward following early-life social deprivation in rats.

PubMed

Lomanowska, Anna M; Kraemer, Gary W

2014-09-01

Early-life social adversity, such as child neglect and institutionalized rearing, is associated with later-life difficulties of inhibitory control that may reflect altered attribution of salience to external stimuli. Studies in rats demonstrate that early-life social deprivation results in enhanced responsiveness to reward stimuli and conditioned reward cues. This study examined whether these effects are related to fundamental changes in appetitive conditioning processes involving instrumental goal-directed and habitual responding for food reward. Rats were reared either by the mother (maternal rearing; MR) or in complete isolation from the mother and litter (artificial rearing; AR) and tested as adults in two appetitive conditioning tasks. AR and MR rats did not differ in the amount of goal-directed effort they exerted to obtain food reward on progressive ratio schedules of reinforcement. AR and MR rats also did not differ in the shift from goal-directed to habitual responding on a random interval schedule and they were equally sensitive to changes in reward value. The major difference between AR and MR rats was that AR rats exhibited more non-instrumental responses (empty food magazine entries, ineffective lever presses). Thus, early-life social deprivation of rats through AR affects the expression of unreinforced extraneous behaviors when motivational requirements are high, but does not affect conditioned goal-directed and habitual responding to reward. The findings have implications for understanding what aspects of responsiveness to external stimuli may be selectively affected in disorders of inhibition associated with early-life social adversity. Copyright © 2014 Elsevier B.V. All rights reserved.

A Learning Center on the Lever for Young Children.

ERIC Educational Resources Information Center

Keislar, Evan R.; Luckenbill, Maryann

This document describes a project designed to explore the possibilities of children's learning in mechanics. The principle of the lever, one example of a simple machine, was used in the form of a balance toy. The apparatus was set up as a game in a specially devised learning center. The children made non-verbal predictions as to which way the bar…

Linking Science with Design and Technology in a Stimulating Approach to Teaching about Levers

ERIC Educational Resources Information Center

Davenport, Carol

2015-01-01

Changes in the National Curriculum for England in 2014 included the introduction of levers, gears, and pulleys into primary science. Although simple mechanisms had been part of the design and technology (DT) curriculum for some time, it was the first time that the science behind the mechanisms had been included at the primary school level. These…

Federal Cooperation in Agricultural Extension Work, Vocational Education, and Vocational Rehabilitation. Bulletin, 1933, No. 15

ERIC Educational Resources Information Center

Blauch, Lloyd E.

1933-01-01

During the past quarter of a century there have been rather continuous and persistent efforts for Federal aid to education. Twenty-one years ago the Congress of the United States enacted the Smith-Lever Agricultural Extension Act, and 3 years later it passed the Smith-Hughes Vocational Education Act. Under the Smith-Lever Act and subsequent…

Model Tests and Computer Simulations of a 15-Barge Tow for the Upper Mississippi River.

DTIC Science & Technology

1984-01-01

8217.* Damping lever ’v Static stability lever - S u’ - Mses of ship No Hf ...... ydrodynamic moment component jpUR about z axis (yawing moment) N Neem ...towboat designed to push an integrated oil barge tow. The second series of tests were performed using the "Exxon Nashville" and the Exxon Lake Charles

Implementing a University E-Learning Strategy: Levers for Change within Academic Schools

ERIC Educational Resources Information Center

Sharpe, Rhona; Benfield, Greg; Francis, Richard

2006-01-01

This paper describes the implementation of an e-learning strategy at a single higher education institution in terms of the levers used to promote effective uptake and ensure sustainable embedding. The focus of this work was at the level of the academic school using a range of change practices including the appointment of school-based learning…

70. DETAIL OF TRACTION CABLE ENGAGEMENT DEVICE. SMALL, KNOBBED LEVER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

70. DETAIL OF TRACTION CABLE ENGAGEMENT DEVICE. SMALL, KNOBBED LEVER ON BUCKET HANGER WAS PULLED DOWN BY A CAMEL (FIXED CAM RAIL AT CENTER) AS BUCKET ROLLED PAST IT, CAUSING A CLAMP TO CLOSE AGAINST TRACTION CABLE. A SIMILAR CAMEL (NO LONGER EXTANT) DISENGAGED CLAMP ON RECEIVING SIDE. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO

49 CFR Appendix A to Part 231 - Schedule of Civil Penalties 1

Code of Federal Regulations, 2010 CFR

2010-10-01

... or Hand Brake Parts Wrong Design 2,500 5,000 114.B2Hand Brake Wheel or Lever Has Insufficient Clearance Around Rim or Handle 2,500 5,000 114.B3Hand Brake Wheel/Lever Clearance Insufficient to Vertical... Improperly Applied 2,500 5,000 146.ANotice or Stencil not Posted on Cabooses with Running Boards Removed 650...

Sexual dimorphism and feeding ecology of Diamond-backed Terrapins (Malaclemys terrapin)

USGS Publications Warehouse

Underwood, Elizabeth B.; Bowers, Sarah; Guzy, Jacquelyn C.; Lovich, Jeffrey E.; Taylor, Carole A.; Gibbons, J. Whitfield; Dorcas, Michael E.

2013-01-01

Natural and sexual selection are frequently invoked as causes of sexual size dimorphism in animals. Many species of turtles, including the Diamond-backed Terrapin (Malaclemys terrapin), exhibit sexual dimorphism in body size, possibly enabling the sexes to exploit different resources and reduce intraspecific competition. Female terrapins not only have larger body sizes but also disproportionately larger skulls and jaws relative to males. To better understand the relationship between skull morphology and terrapin feeding ecology, we measured the in-lever to out-lever ratios of 27 male and 33 female terrapin jaws to evaluate biomechanics of the trophic apparatus. In addition, we measured prey handling times by feeding Fiddler Crabs (Uca pugnax), a natural prey item, to 24 terrapins in the laboratory. Our results indicate that although females have disproportionately larger heads, they have similar in:out lever ratios to males, suggesting that differences in adductor muscle mass are more important in determining bite force than jaw in:out lever ratios. Females also had considerably reduced prey handling times. Understanding the factors affecting terrapin feeding ecology can illuminate the potential roles male and female terrapins play as top-down predators that regulate grazing of Periwinkle Snails (Littorina irrorata) on Cord Grass (Spartina alterniflora).

Effect of cantilever geometry on the optical lever sensitivities and thermal noise method of the atomic force microscope.

PubMed

Sader, John E; Lu, Jianing; Mulvaney, Paul

2014-11-01

Calibration of the optical lever sensitivities of atomic force microscope (AFM) cantilevers is especially important for determining the force in AFM measurements. These sensitivities depend critically on the cantilever mode used and are known to differ for static and dynamic measurements. Here, we calculate the ratio of the dynamic and static sensitivities for several common AFM cantilevers, whose shapes vary considerably, and experimentally verify these results. The dynamic-to-static optical lever sensitivity ratio is found to range from 1.09 to 1.41 for the cantilevers studied - in stark contrast to the constant value of 1.09 used widely in current calibration studies. This analysis shows that accuracy of the thermal noise method for the static spring constant is strongly dependent on cantilever geometry - neglect of these dynamic-to-static factors can induce errors exceeding 100%. We also discuss a simple experimental approach to non-invasively and simultaneously determine the dynamic and static spring constants and optical lever sensitivities of cantilevers of arbitrary shape, which is applicable to all AFM platforms that have the thermal noise method for spring constant calibration.

Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension.

PubMed

Li, Jianchao; Chen, Yiyun; Deng, Yisong; Unarta, Ilona Christy; Lu, Qing; Huang, Xuhui; Zhang, Mingjie

2017-04-04

Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca 2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca 2+ -CaM remains bound to IQ5-SAH, the Ca 2+ -induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca 2+ -induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca 2+ -CaM, suggesting a common Ca 2+ -induced conformational regulation mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of di-amphetamine injected into N. Accumbens on ethanol self-administration in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samson, H.H.; Tolliver, G.A.; Haraguchi, M.

1991-03-11

Adult, male Long-Evans rats were initiated to lever press with 10% (v/v) ethanol reinforcement using the sucrose-fading technique. Following initiation and the development of stable ethanol self-administration behavior, bilateral cannula guides directed at the N.Accumbens were surgically implanted. Following recovery, the animals received microinjections once a week of either saline, 4, 10 or 20 ug/brain of dl-amphetamine sulfate dissolved in saline. Injections were 10 minutes prior to the daily 30min ethanol self-administration session.; At all doses tested, amphetamine had no significant effect upon the number of responses or ethanol. Reinforcements received during the session. However, a clear alteration in themore » pattern of responding was found at the 10 and 20 ug dose, with some animals showing effects at 4 ug. This alteration in response pattern with no effect upon total responding is different from prior work using systemic amphetamine injections, where both pattern and number of responses were affected. The data suggest that some but not all of the systemic effects could be related to amphetamine's actions on the N. Accumbens.« less

Dual Optical Levers for Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Kawakatsu, Hideki; Bleuler, Hannes; Saito, Takashi; Hiroshi, Kougami

1995-06-01

Development of micro machined cantilever and optical lever detection system has greatly facilitated the operation of atomic force microscopy. However, since the detection system measures only the deflection of the cantilever at one set point where the laser beam is focused, care must be taken in implementing force control or in interpreting the acquired data. In this paper, a dual optical lever detection system is introduced, which has the potential to resolve the deformation of the cantilever with multidegree of freedom and thus detect the position of the tip end point with resolution in the 10 pm order. The detection system proved to be effective in real-time monitoring of the behavior of the tip end point while scanning, and in explaining the scanning direction dependence of the acquired images.

Dorsolateral neostriatum contribution to incentive salience: Opioid or dopamine stimulation makes one reward cue more motivationally attractive than another

PubMed Central

DiFeliceantonio, Alexandra G.; Berridge, Kent C.

2016-01-01

Pavlovian cues for rewards can become attractive incentives: approached and ‘wanted’ as the rewards themselves. The motivational attractiveness of a previously learned cue is not fixed, but can be dynamically amplified during re-encounter by simultaneous activation of brain limbic circuitry. Here we report that opioid or dopamine microinjections in the dorsolateral quadrant of the neostriatum (DLS) of rats selectively amplify attraction toward a previously learned Pavlovian cue in an individualized fashion, at the expense of a competing cue. In an autoshaping (sign-tracking vs goal-tracking) paradigm, microinjection of the mu opioid receptor agonist (DAMGO) or dopamine indirect agonist (amphetamine) in DLS of sign-tracker individuals selectively enhanced their sign-tracking attraction toward the reward-predictive lever cue. By contrast, DAMGO or amphetamine in DLS of goal-trackers selectively enhanced prepotent attraction toward the reward-proximal cue of sucrose dish. Amphetamine also enhanced goal-tracking in some sign-tracker individuals (if they ever defected to the dish even once). That DLS enhancement of cue attraction was due to stronger motivation, not stronger habits was suggested by: 1) sign-trackers flexibly followed their cue to a new location when the lever was suddenly moved after DLS DAMGO microinjection, and 2) DAMGO in DLS also made sign-trackers work harder on a new instrumental nose-poke response required to earn presentations of their Pavlovian lever cue (instrumental conditioned reinforcement). Altogether, our results suggest that DLS circuitry can enhance the incentive salience of a Pavlovian reward cue, selectively making that cue a stronger motivational magnet. PMID:26924040

Effects of toluene inhalation on detection of auditory signals in rats.

PubMed

Bushnell, P J; Kelly, K L; Crofton, K M

1994-01-01

Inhalation of organic solvents can affect vigilance and reaction time in humans. An animal model of vigilance was designed to assess the effects of toluene on these processes. Adult male Long-Evans rats were trained to detect auditory signals (20-msec increases in the intensity of white noise). Two to 4 s after each signal (or blank period), two retractable levers were inserted into the test chamber. A press on one lever after a signal and on the other lever after a blank resulted in the delivery of food. Signal detection analysis showed that sensitivity (Sensitivity Index, SI) and response bias (Responsivity Index, RI) increased with signal intensity, indicating that loud signals were more detectable than soft signals and that the animals' criterion for responding "signal" increased with signal intensity. Response latency for correct choices was faster for signal trials than for blank trials. Toluene vapor was added to the airstream of these chambers at concentrations of 0, 1000, 1500, or 2000 ppm, either 10 or 30 min before testing and for the duration of each 1-h test. In air, SI increased across the duration of the test; this within-session improvement was reversed by toluene. RI did not change in air; it was decreased by toluene at the beginning of each exposure session, returned to the control level during exposure to 1000 and 1500 ppm toluene and exceeded air control after 40 min exposure to 2000 ppm toluene. Latency increased monotonically across toluene concentrations and time on test. Neither signal intensity nor the duration of toluene exposure before testing altered these effects of toluene. SI, RI, and latency baselines were recovered after toluene exposure indicating that no persistent effects of toluene were detectable. This conclusion was supported by data from other rats showing that toluene exposure (2000 ppm for 2 h/day for 4 consecutive days) did not affect auditory thresholds, as determined by reflex modification of an acoustic startle response using a 16 kHz tone as a prepulse stimulus, 7 or 17 days after exposure to toluene. Finally, rats tested immediately or 20 min after exposure to 0, 1000, 1500, or 2000 ppm toluene were not affected by the vapor, indicating that the impairment observed during toluene inhalation did not persist beyond the period of exposure.

Dynamics of Choice: Relative Rate and Amount Affect Local Preference at Three Different Time Scales

ERIC Educational Resources Information Center

Aparicio, Carlos F.; Baum, William M.

2009-01-01

To examine extended control over local choice, the present study investigated preference in transition as food-rate ratio provided by two levers changed across seven components within daily sessions, and food-amount ratio changed across phases. Phase 1 arranged a food-amount ratio of 4:1 (i.e., the left lever delivered four pellets and the right…

The Effects of Behavioral History on Response Acquisition with Immediate and Delayed Reinforcement

ERIC Educational Resources Information Center

Snycerski, Susan; Laraway, Sean; Huitema, Bradley E.; Poling, Alan

2004-01-01

Effects of prior exposure to the experimental chamber with levers present or absent and variable-time (VT) 60-s water deliveries arranged during one, five, or no 1-hr sessions were examined in rats during a 6-hr response-acquisition session in which presses on one lever produced water delivery immediately or after a 15-s resetting delay, and…

Sow the Seeds of Victory! Posters from the Food Administration during World War I. The Constitution Community: The Emergence of Modern America (1890-1930).

ERIC Educational Resources Information Center

Simmons, Linda

From the outbreak of World War I in Europe until the signing of the Versailles Treaty, President Woodrow Wilson's administration proposed and implemented an extraordinary number of programs that affected people in their everyday activities. In August 1917 Congress passed the Food and Fuel Control Act, also known as the Lever Act, which gave the…

The jaw is a second-class lever in Pedetes capensis (Rodentia: Pedetidae)

PubMed Central

2017-01-01

The mammalian jaw is often modelled as a third-class lever for the purposes of biomechanical analyses, owing to the position of the resultant muscle force between the jaw joint and the teeth. However, it has been proposed that in some rodents the jaws operate as a second-class lever during distal molar bites, owing to the rostral position of the masticatory musculature. In particular, the infraorbital portion of the zygomatico-mandibularis (IOZM) has been suggested to be of major importance in converting the masticatory system from a third-class to a second-class lever. The presence of the IOZM is diagnostic of the hystricomorph rodents, and is particularly well-developed in Pedetes capensis, the South African springhare. In this study, finite element analysis (FEA) was used to assess the lever mechanics of the springhare masticatory system, and to determine the function of the IOZM. An FE model of the skull of P. capensis was constructed and loaded with all masticatory muscles, and then solved for biting at each tooth in turn. Further load cases were created in which each masticatory muscle was removed in turn. The analyses showed that the mechanical advantage of the springhare jaws was above one at all molar bites and very close to one during the premolar bite. Removing the IOZM or masseter caused a drop in mechanical advantage at all bites, but affected strain patterns and cranial deformation very little. Removing the ZM had only a small effect on mechanical advantage, but produced a substantial reduction in strain and deformation across the skull. It was concluded that the masticatory system of P. capensis acts as a second class lever during bites along almost the entire cheek tooth row. The IOZM is clearly a major contributor to this effect, but the masseter also has a part to play. The benefit of the IOZM is that it adds force without substantially contributing to strain or deformation of the skull. This may help explain why the hystricomorphous morphology has evolved multiple times independently within Rodentia. PMID:28875081

Parrotfish grazing ability: interspecific differences in relation to jaw-lever mechanics and relative weight of adductor mandibulae on an Okinawan coral reef

PubMed Central

2016-01-01

Parrotfishes (family Labridae: Scarini) are regarded to have important roles for maintaining the ecosystem balance in coral reefs due to their removal of organic matter and calcic substrates by grazing. The purpose of the present study was to clarify the interspecific differences in grazing ability of five parrotfish species (Chlorurus sordidus, C. bowersi, Scarus rivulatus, S. niger and S. forsteni) in relation to interspecific differences in jaw-lever mechanics and the relative weight of the adductor mandibulae (muscles operating jaw closing). The grazing ability was calculated by using stomach contents (CaCO3 weight/organic matter weight) defined as the grazing ability index (GAI). There were significant interspecific differences in GAI (C. sordidus = C. bowersi > S. rivulatus > S. niger = S. forsteni). Teeth of C. sordidus and C. bowersi were protrusive-shape whereas teeth of S. rivulatus, S. niger and S. forsteni were flat-shape. C. sordidus and C. bowersihave jaw-lever mechanics producing a greater biting force and have a larger weight of adductor mandibulae. S. rivulatus has jaw-lever mechanics producing a greater biting force but a smaller weight of adductor mandibulae that produce an intermediate biting force. In contrast, S. niger and S. forsteni have jaw-lever mechanics producing a lesser biting force and have a smaller weight of adductor mandibulae. Feeding rates and foray size of S. rivulatus, S. niger and S. forsteni were greater than C. sordidus and C. bowersi. The degree in bioerosion (GAI × feeding rate) was the largest for S. rivulatusand the smallest for S. forsteni. The degree in bioerosion for C. sordidus was larger than S. niger whereas relatively equal between C. bowersi and S. niger. These results suggest that interspecific difference in GAI was explained by interspecific differences in teeth shape, jaw-lever mechanics and relative weight of adductor mandibulae. The interspecific difference in the degree of bioerosion suggests the importance of various size of parrotfishes with diverse feeding modes to maintain healthy coral reef ecosystems. PMID:27635364

Parrotfish grazing ability: interspecific differences in relation to jaw-lever mechanics and relative weight of adductor mandibulae on an Okinawan coral reef.

PubMed

Nanami, Atsushi

2016-01-01

Parrotfishes (family Labridae: Scarini) are regarded to have important roles for maintaining the ecosystem balance in coral reefs due to their removal of organic matter and calcic substrates by grazing. The purpose of the present study was to clarify the interspecific differences in grazing ability of five parrotfish species (Chlorurus sordidus, C. bowersi, Scarus rivulatus, S. niger and S. forsteni) in relation to interspecific differences in jaw-lever mechanics and the relative weight of the adductor mandibulae (muscles operating jaw closing). The grazing ability was calculated by using stomach contents (CaCO3 weight/organic matter weight) defined as the grazing ability index (GAI). There were significant interspecific differences in GAI (C. sordidus = C. bowersi > S. rivulatus > S. niger = S. forsteni). Teeth of C. sordidus and C. bowersi were protrusive-shape whereas teeth of S. rivulatus, S. niger and S. forsteni were flat-shape. C. sordidus and C. bowersihave jaw-lever mechanics producing a greater biting force and have a larger weight of adductor mandibulae. S. rivulatus has jaw-lever mechanics producing a greater biting force but a smaller weight of adductor mandibulae that produce an intermediate biting force. In contrast, S. niger and S. forsteni have jaw-lever mechanics producing a lesser biting force and have a smaller weight of adductor mandibulae. Feeding rates and foray size of S. rivulatus, S. niger and S. forsteni were greater than C. sordidus and C. bowersi. The degree in bioerosion (GAI × feeding rate) was the largest for S. rivulatusand the smallest for S. forsteni. The degree in bioerosion for C. sordidus was larger than S. niger whereas relatively equal between C. bowersi and S. niger. These results suggest that interspecific difference in GAI was explained by interspecific differences in teeth shape, jaw-lever mechanics and relative weight of adductor mandibulae. The interspecific difference in the degree of bioerosion suggests the importance of various size of parrotfishes with diverse feeding modes to maintain healthy coral reef ecosystems.

Trap gun: an unusual firearm, aimed at wild animals but causing a silent epidemic of human fatalities.

PubMed

Kodikara, Sarathchandra; Kudagama, Muditha

2014-03-01

Among a variety of uncommon firearms of different origin used worldwide, the trap gun used in Sri Lanka is underreported. This is an illegal, locally made, smooth-bore, long-barreled, muzzle-loading firearm with a victim-activated simple trigger mechanism. It is mainly used to protect crops and livestock from the potential harm by wild animals. Trap gun is mounted horizontally on pegs of sticks fixed to the ground. Miscellaneous metal pieces are used as ammunition. A small metal container filled with powdered matchstick heads/firecrackers covered by the striker surface of the matchstick box is used as the percussion cap. A metal hammer is set to hit the percussion cap. Through a lever mechanism, the hammer is kept under tension. The lever mechanism is connected to a trigger cord, which runs across the animal path. The first passerby, a human being or a wild animal, who accidentally trips the trigger cord and activates the trigger mechanism is critically injured. This characteristically damages the lower limbs of the human being. This communication highlights a death due to trap gun injury. The injury pattern caused by trap gun could overlap with that of shotgun and rifled firearm. A meticulous autopsy could sort it out.

Effects of restricted feeding schedules on circadian organization in squirrel monkeys

NASA Technical Reports Server (NTRS)

Boulos, Z.; Frim, D. M.; Dewey, L. K.; Moore-Ede, M. C.

1989-01-01

Free running circadian rhythms of motor activity, food-motivated lever-pressing, and either drinking (N = 7) or body temperature (N = 3) were recorded from 10 squirrel monkeys maintained in constant illumination with unlimited access to food. Food availability was then restricted to a single unsignaled 3-hour interval each day. The feeding schedule failed to entrain the activity rhythms of 8 monkeys, which continued to free-run. Drinking was almost completely synchronized by the schedule, while body temperature showed a feeding-induced rise superimposed on a free-running rhythm. Nonreinforced lever-pressing showed both a free-running component and a 24-hour component that anticipated the time of feeding. At the termination of the schedule, all recorded variables showed free-running rhythms, but in 3 animals the initial phase of the postschedule rhythms was advanced by several hours, suggesting relative coordination. Of the remaining 2 animals, one exhibited stable entrainment of all 3 recorded rhythms, while the other appeared to entrain temporarily to the feeding schedule. These results indicate that restricted feeding schedules are only a weak zeitgeber for the circadian pacemaker generating free-running rhythms in the squirrel monkey. Such schedules, however, may entrain a separate circadian system responsible for the timing of food-anticipatory changes in behavior and physiology.

A Case for Application Oblivious Energy-Efficient MPI Runtime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venkatesh, Akshay; Vishnu, Abhinav; Hamidouche, Khaled

Power has become the major impediment in designing large scale high-end systems. Message Passing Interface (MPI) is the {\\em de facto} communication interface used as the back-end for designing applications, programming models and runtime for these systems. Slack --- the time spent by an MPI process in a single MPI call --- provides a potential for energy and power savings, if an appropriate power reduction technique such as core-idling/Dynamic Voltage and Frequency Scaling (DVFS) can be applied without perturbing application's execution time. Existing techniques that exploit slack for power savings assume that application behavior repeats across iterations/executions. However, an increasingmore » use of adaptive, data-dependent workloads combined with system factors (OS noise, congestion) makes this assumption invalid. This paper proposes and implements Energy Aware MPI (EAM) --- an application-oblivious energy-efficient MPI runtime. EAM uses a combination of communication models of common MPI primitives (point-to-point, collective, progress, blocking/non-blocking) and an online observation of slack for maximizing energy efficiency. Each power lever incurs time overhead, which must be amortized over slack to minimize degradation. When predicted communication time exceeds a lever overhead, the lever is used {\\em as soon as possible} --- to maximize energy efficiency. When mis-prediction occurs, the lever(s) are used automatically at specific intervals for amortization. We implement EAM using MVAPICH2 and evaluate it on ten applications using up to 4096 processes. Our performance evaluation on an InfiniBand cluster indicates that EAM can reduce energy consumption by 5--41\\% in comparison to the default approach, with negligible (less than 4\\% in all cases) performance loss.« less

Cognitive Judgment Bias Interacts with Risk Based Decision Making and Sensitivity to Dopaminergic Challenge in Male Rats

PubMed Central

Drozd, Robert; Cieslak, Przemyslaw E.; Rychlik, Michal; Rodriguez Parkitna, Jan; Rygula, Rafal

2016-01-01

Although the cognitive theory has implicated judgment bias in various psychopathologies, its role in decision making under risk remains relatively unexplored. In the present study, we assessed the effects of cognitive judgment bias on risky choices in rats. First, we trained and tested the animals on the rat version of the probability-discounting (PD) task. During discrete trials, the rats chose between two levers; a press on the “small/certain” lever always resulted in the delivery of one reward pellet, whereas a press on the “large/risky” lever resulted in the delivery of four pellets. However, the probability of receiving a reward from the “large/risky” lever gradually decreased over the four trial blocks. Subsequently, the rats were re-trained and evaluated on a series of ambiguous-cue interpretation (ACI) tests, which permitted their classification according to the display of “optimistic” or “pessimistic” traits. Because dopamine (DA) has been implicated in both: risky choices and optimism, in the last experiment, we compared the reactivity of the dopaminergic system in the “optimistic” and “pessimistic” animals using the apomorphine (APO; 2 mg/kg s.c.) sensitivity test. We demonstrated that as risk increased, the proportion of risky lever choices decreased significantly slower in “optimists” compared with “pessimists” and that these differences between the two groups of rats were associated with different levels of dopaminergic system reactivity. Our findings suggest that cognitive judgment bias, risky decision-making and DA are linked, and they provide a foundation for further investigation of the behavioral traits and cognitive processes that influence risky choices in animal models. PMID:27601984

Anabolic-androgenic steroids alter decision making in a balanced rodent model of the Iowa gambling task.

PubMed

Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana; Wood, Ruth I

2018-06-01

Anabolic-androgenic steroid (AAS) abuse is implicated in maladaptive decision making such as increased risk taking and problem gambling. Endogenous testosterone correlates with economic risk taking in both the stock market (Coates & Herbert, 2008) and in the laboratory, as measured by the Iowa Gambling Task (Stanton, Liening, & Schultheiss, 2011). Additionally, AAS use has been associated with problem gambling behavior in adolescents (Proimos, DuRant, Pierce, & Goodman, 1998). Thus, AAS may impair economic decision making. However, studies of human AAS users cannot control for preexisting risky behavior or normalize androgen levels. Accordingly, the present study investigated AAS effects on decision making in rats using a novel, balanced rodent model of the IGT. Adolescent male Long-Evans rats were treated chronically with high-dose testosterone (7.5 mg/kg) or vehicle (13% cyclodextrin in water) sc, and trained to work for sugar pellets in an operant chamber equipped with 4 levers, each associated with a different schedule of reward magnitude (number of pellets), probability, and punishment (time-out) duration. By RM-ANOVA, there was a main effect of lever (F3,78 = 25.33, p < .05), such that all rats preferred lever L4 offering a large reward (4 pellets), but with low probability (45%) and a long (35 sec) time-out. There was also a significant interaction of testosterone × lever (F3,78 = 2.78, p < .05), with testosterone increasing preference for L4 and decreasing preference for the other levers, relative to vehicle-treated controls. These data extend our previous findings of altered decision making in AAS-treated rats, and suggest that AAS may alter economic decision making in human users. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Nucleus accumbens opioid, GABaergic, and dopaminergic modulation of palatable food motivation: contrasting effects revealed by a progressive ratio study in the rat.

PubMed

Zhang, Min; Balmadrid, Christian; Kelley, Ann E

2003-04-01

The current studies were designed to evaluate whether incentive motivation for palatable food is altered after manipulations of opioid, GABAergic, and dopaminergic transmission within the nucleus accumbens. A progressive ratio schedule was used to measure lever-pressing for sugar pellets after microinfusion of drugs into the nucleus accumbens in non-food-deprived rats. The mu opioid agonist D-Ala2, NMe-Phe4, Glyo15-enkephalin and the indirect dopamine agonist amphetamine induced a marked increase in break point and correct lever-presses; the GABA(A) agonist muscimol did not affect breakpoint or lever-presses. The data suggest that opioid, dopaminergic, and GABAergic systems within the accumbens differentially modulate food-seeking behavior through mechanisms related to hedonic evaluation of food, incentive salience, and control of motor feeding circuits, respectively.

Thrust performance of unsteady propulsors using a novel measurement system, and corresponding wake patterns

PubMed Central

Clark, Richard P.; Smits, Alexander J.

2009-01-01

An apparatus is described for the measurement of unsteady thrust and propulsive efficiency produced by biologically inspired oscillating hydrodynamic propulsors. Force measurement is achieved using a strain-gauge-based force transducer, augmented with a lever to amplify or attenuate the applied force and control the measurement sensitivity and natural frequency of vibration. The lever can be used to tune the system to a specific application and it is shown that, using the lever, the stiffness can be made to increase more rapidly than the measurement sensitivity decreases. Efficiency is computed from measurements of the time-averaged power imparted to the fluid. The apparatus is applied to two different propulsors, demonstrating the versatility of the system; wake visualizations are examined, which provide insight into the physical mechanisms of efficient propulsion. PMID:19946574

Effects of Reinforcer Probability, Delay, and Response Requirements on the Choices of Rats and Pigeons: Possible Species Differences

ERIC Educational Resources Information Center

Mazur, James E.

2005-01-01

In Experiment 1 with rats, a left lever press led to a 5-s delay and then a possible reinforcer. A right lever press led to an adjusting delay and then a certain reinforcer. This delay was adjusted over trials to estimate an indifference point, or a delay at which the two alternatives were chosen about equally often. Indifference points increased…

Sterile Reverse Osmosis Water Combined with Friction Are Optimal for Channel and Lever Cavity Sample Collection of Flexible Duodenoscopes.

PubMed

Alfa, Michelle J; Singh, Harminder; Nugent, Zoann; Duerksen, Donald; Schultz, Gale; Reidy, Carol; DeGagne, Patricia; Olson, Nancy

2017-01-01

Simulated-use buildup biofilm (BBF) model was used to assess various extraction fluids and friction methods to determine the optimal sample collection method for polytetrafluorethylene channels. In addition, simulated-use testing was performed for the channel and lever cavity of duodenoscopes. BBF was formed in polytetrafluorethylene channels using Enterococcus faecalis, Escherichia coli , and Pseudomonas aeruginosa . Sterile reverse osmosis (RO) water, and phosphate-buffered saline with and without Tween80 as well as two neutralizing broths (Letheen and Dey-Engley) were each assessed with and without friction. Neutralizer was added immediately after sample collection and samples concentrated using centrifugation. Simulated-use testing was done using TJF-Q180V and JF-140F Olympus duodenoscopes. Despite variability in the bacterial CFU in the BBF model, none of the extraction fluids tested were significantly better than RO. Borescope examination showed far less residual material when friction was part of the extraction protocol. The RO for flush-brush-flush (FBF) extraction provided significantly better recovery of E. coli ( p  = 0.02) from duodenoscope lever cavities compared to the CDC flush method. We recommend RO with friction for FBF extraction of the channel and lever cavity of duodenoscopes. Neutralizer and sample concentration optimize recovery of viable bacteria on culture.

Behavioral regulation of gravity: schedule effects under escape-avoidance procedures1

PubMed Central

Clark, Fogle C.; Lange, Karl O.; Belleville, Richard E.

1973-01-01

Squirrel monkeys were restrained in a centrifuge capsule and trained to escape and avoid increases in artificial gravity. During escape-avoidance, lever responses reduced centrifugally simulated gravity or postponed scheduled increases. The effect of variation in the interval of postponement (equal to the duration of decrease produced by escape responses) was studied under a multiple schedule of four components. Three components were gravity escape-avoidance with postponement times of 20, 40, and 60 sec. The fourth component was extinction. Each component was associated with a different auditory stimulus. Rate of responding decreased with increasing postponement time and higher mean g-levels occurred at shorter intervals of postponement. Effects of the schedule parameter on response rate and mean g-level were similar to effects of the schedule on free-operant avoidance and on titration behavior maintained by shock. ImagesFig. 1. PMID:4202386

Discriminative echolocation in a porpoise, 12

PubMed Central

Turner, Ronald N.; Norris, Kenneth S.

1966-01-01

Operant conditioning techniques were used to establish a discriminative echolocation performance in a porpoise. Pairs of spheres of disparate diameters were presented in an under-water display, and the positions of the spheres were switched according to a scrambled sequence while the blindfolded porpoise responded on a pair of submerged response levers. Responses which identified the momentary state of the display were food-reinforced, while those which did not (errors) produced time out. Errors were then studied in relation to decreased disparity between the spheres. As disparity was decreased, errors which terminated runs of correct responses occurred more frequently and were followed by longer strings of consecutive errors. Increased errors and disruption of a stable pattern of collateral behavior were associated. Since some sources of error other than decreased disparity were present, the porpoise's final performance did not fully reflect the acuity of its echolocation channel. PMID:5964509

The rat approximates an ideal detector of changes in rates of reward: implications for the law of effect.

PubMed

Gallistel, C R; Mark, T A; King, A P; Latham, P E

2001-10-01

Rats responded on 2 levers delivering brain stimulation reward on concurrent variable interval schedules. Following many successive sessions with unchanging relative rates of reward, subjects adjusted to an eventual change slowly and showed spontaneous reversions at the beginning of subsequent sessions. When changes in rates of reward occurred between and within every session, subjects adjusted to them about as rapidly as they could in principle do so, as shown by comparison to a Bayesian model of an ideal detector. This and other features of the adjustments to frequent changes imply that the behavioral effect of reinforcement depends on the subject's perception of incomes and changes in incomes rather than on the strengthening and weakening of behaviors in accord with their past effects or expected results. Models for the process by which perceived incomes determine stay durations and for the process that detects changes in rates are developed.

Kinetics of matching.

PubMed

Mark, T A; Gallistel, C R

1994-01-01

Rats responded on concurrent variable interval schedules of brain stimulation reward in 2-trial sessions. Between trials, there was a 16-fold reversal in the relative rate of reward. In successive, narrow time windows, the authors compared the ratio of the times spent on the 2 levers to the ratio of the rewards received. Time-allocation ratios tracked wide, random fluctuations in the reward ratio. The adjustment to the midsession reversal in relative rate of reward was largely completed within 1 interreward interval on the leaner schedule. Both results were unaffected by a 16-fold change in the combined rates of reward. The large, rapid, scale-invariant shifts in time-allocation ratios that underlie matching behavior imply that the subjective relative rate of reward can be determined by a very few of the most recent interreward intervals and that this estimate can directly determine the ratio of the expected stay durations.

Inactivation of the Prelimbic Cortex Attenuates Context-Dependent Operant Responding.

PubMed

Trask, Sydney; Shipman, Megan L; Green, John T; Bouton, Mark E

2017-03-01

Operant responding in rats provides an analog to voluntary behavior in humans and is used to study maladaptive behaviors, such as overeating, drug taking, or relapse. In renewal paradigms, extinguished behavior recovers when tested outside the context where extinction was learned. Inactivation of the prelimbic (PL) region of the medial prefrontal cortex by baclofen/muscimol (B/M) during testing attenuates renewal when tested in the original acquisition context after extinction in another context (ABA renewal). Two experiments tested the hypothesis that the PL is important in context-dependent responding learned during conditioning. In the first, rats learned to lever-press for a sucrose-pellet reward. Following acquisition, animals were infused with either B/M or vehicle in the PL and tested in the acquisition context (A) and in a different context (B). All rats showed a decrement in responding when switched from Context A to Context B, but PL inactivation decreased responding only in Context A. Experiment 2a examined the effects of PL inactivation on ABC renewal in the same rats. Here, following reacquisition of the response, responding was extinguished in a new context (C). Following infusions of B/M or vehicle in the PL, responding was tested in Context C and another new context (D). The rats exhibited ACD renewal regardless of PL inactivation. Experiment 2b demonstrated that PL inactivation attenuated the ABA renewal effect in the same animals, replicating earlier results and demonstrating that cannulae were still functional. The results suggest that, rather than attenuating renewal generally, PL inactivation specifically affects ABA renewal by reducing responding in the conditioning context. SIGNIFICANCE STATEMENT Extinguished operant behavior can recover ("renew") when tested outside the extinction context. This suggests that behaviors, such as overeating or drug taking, might be especially prone to relapse following treatment. In rats, inactivation of the prelimbic cortex (PL) attenuates renewal. However, we report that PL inactivation after training attenuates responding in the context in which responding was acquired, but not in another one. A similar inactivation has no impact on renewal when testing occurs in a new, rather than the original, context following extinction. The PL thus has a more specific role in controlling contextually dependent operant behavior than has been previously reported. Copyright © 2017 the authors 0270-6474/17/372317-08$15.00/0.

Inactivation of the Prelimbic Cortex Attenuates Context-Dependent Operant Responding

PubMed Central

Shipman, Megan L.; Bouton, Mark E.

2017-01-01

Operant responding in rats provides an analog to voluntary behavior in humans and is used to study maladaptive behaviors, such as overeating, drug taking, or relapse. In renewal paradigms, extinguished behavior recovers when tested outside the context where extinction was learned. Inactivation of the prelimbic (PL) region of the medial prefrontal cortex by baclofen/muscimol (B/M) during testing attenuates renewal when tested in the original acquisition context after extinction in another context (ABA renewal). Two experiments tested the hypothesis that the PL is important in context-dependent responding learned during conditioning. In the first, rats learned to lever-press for a sucrose-pellet reward. Following acquisition, animals were infused with either B/M or vehicle in the PL and tested in the acquisition context (A) and in a different context (B). All rats showed a decrement in responding when switched from Context A to Context B, but PL inactivation decreased responding only in Context A. Experiment 2a examined the effects of PL inactivation on ABC renewal in the same rats. Here, following reacquisition of the response, responding was extinguished in a new context (C). Following infusions of B/M or vehicle in the PL, responding was tested in Context C and another new context (D). The rats exhibited ACD renewal regardless of PL inactivation. Experiment 2b demonstrated that PL inactivation attenuated the ABA renewal effect in the same animals, replicating earlier results and demonstrating that cannulae were still functional. The results suggest that, rather than attenuating renewal generally, PL inactivation specifically affects ABA renewal by reducing responding in the conditioning context. SIGNIFICANCE STATEMENT Extinguished operant behavior can recover (“renew”) when tested outside the extinction context. This suggests that behaviors, such as overeating or drug taking, might be especially prone to relapse following treatment. In rats, inactivation of the prelimbic cortex (PL) attenuates renewal. However, we report that PL inactivation after training attenuates responding in the context in which responding was acquired, but not in another one. A similar inactivation has no impact on renewal when testing occurs in a new, rather than the original, context following extinction. The PL thus has a more specific role in controlling contextually dependent operant behavior than has been previously reported. PMID:28137970

Simulating the impact of long-term care policy on family eldercare hours.

PubMed

Ansah, John P; Matchar, David B; Love, Sean R; Malhotra, Rahul; Do, Young Kyung; Chan, Angelique; Eberlein, Robert

2013-04-01

To understand the effect of current and future long-term care (LTC) policies on family eldercare hours for older adults (60 years of age and older) in Singapore. The Social Isolation Health and Lifestyles Survey, the Survey on Informal Caregiving, and the Singapore Government's Ministry of Health and Department of Statistics. An LTC Model was created using system dynamics methodology and parameterized using available reports and data as well as informal consultation with LTC experts. In the absence of policy change, among the elderly living at home with limitations in their activities of daily living (ADLs), the proportion of those with greater ADL limitations will increase. In addition, by 2030, average family eldercare hours per week are projected to increase by 41 percent from 29 to 41 hours. All policy levers considered would moderate or significantly reduce family eldercare hours. System dynamics modeling was useful in providing policy makers with an overview of the levers available to them and in demonstrating the interdependence of policies and system components. © Health Research and Educational Trust.

Novel adaptive fiber-optics collimator for coherent beam combination.

PubMed

Zhi, Dong; Ma, Pengfei; Ma, Yanxing; Wang, Xiaolin; Zhou, Pu; Si, Lei

2014-12-15

In this manuscript, we experimentally validate a novel design of adaptive fiber-optics collimator (AFOC), which utilizes two levers to enlarge the movable range of the fiber end cap. The enlargement of the range makes the new AFOC possible to compensate the end-cap/tilt aberration in fiber laser beam combining system. The new AFOC based on flexible hinges and levers was fabricated and the performance of the new AFOC was tested carefully, including its control range, frequency response and control accuracy. Coherent beam combination (CBC) of two 5-W fiber amplifiers array with simultaneously end-cap/tilt control and phase-locking control was implemented successfully with the novel AFOC. Experimental results show that the average normalized power in the bucket (PIB) value increases from 0.311 to 0.934 with active phasing and tilt aberration compensation simultaneously, and with both controls on, the fringe contrast improves to more than 82% from 0% for the case with both control off. This work presents a promising structure for tilt aberration control in high power CBC system.

Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys.

PubMed

Maguire, David R; France, Charles P

2016-04-01

Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32-32 μg/kg/infusion, intravenously) generated an inverted U-shaped dose-effect curve. Administered acutely, Δ-THC (0.01-0.32 mg/kg, subcutaneously) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ-THC (0.01-0.1 mg/kg/12 h, subcutaneously) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.

The Sensory Features of a Food Cue Influence Its Ability to Act as an Incentive Stimulus and Evoke Dopamine Release in the Nucleus Accumbens Core

ERIC Educational Resources Information Center

Singer, Bryan F.; Bryan, Myranda A.; Popov, Pavlo; Scarff, Raymond; Carter, Cody; Wright, Erin; Aragona, Brandon J.; Robinson, Terry E.

2016-01-01

The sensory properties of a reward-paired cue (a conditioned stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual…

Effects of adolescent exposure to methylmercury and d-amphetamine on reversal learning and an extradimensional shift in male mice

PubMed Central

Boomhower, Steven R.; Newland, M. Christopher

2016-01-01

Adolescence is associated with the continued maturation of dopamine neurotransmission and is implicated in the etiology of many psychiatric illnesses. Adolescent exposure to neurotoxicants that distort dopamine neurotransmission, such as methylmercury (MeHg), may modify the effects of chronic d-amphetamine (d-AMP) administration on reversal learning and attentional-set shifting. Male C57Bl/6n mice were randomly assigned to two MeHg-exposure groups (0 ppm and 3 ppm) and two d-AMP-exposure groups (saline and 1 mg/kg/day), producing four treatment groups (n = 10–12/group): Control, MeHg, d-AMP, and MeHg + d-AMP. MeHg exposure (via drinking water) spanned postnatal day 21–59 (the murine adolescent period), and once daily i.p. injections of d-AMP or saline spanned postnatal day 28–42. As adults, mice were trained on a spatial-discrimination-reversal (SDR) task in which the spatial location of a lever press predicted reinforcement. Following two SDRs, a visual-discrimination task (extradimensional shift) was instated in which the presence of a stimulus light above a lever predicted reinforcement. Responding was modeled using a logistic function, which estimated the rate (slope) of a behavioral transition and trials required to complete half a transition (half-max). MeHg, d-AMP, and MeHg + d-AMP exposure increased estimates of half-max on the second reversal. MeHg exposure increased half-max and decreased the slope term following the extradimensional shift, but these effects did not occur following MeHg + d-AMP exposure. MeHg + d-AMP exposure produced more perseverative errors and omissions following a reversal. Adolescent exposure to MeHg can modify the behavioral effects of chronic d-AMP administration. PMID:28287789

Adolescent d-Amphetamine Treatment in a Rodent Model of ADHD: Pro-Cognitive Effects in Adolescence without an Impact on Cocaine Cue Reactivity in Adulthood

PubMed Central

Jordan, Chloe J.; Taylor, Danielle M.; Dwoskin, Linda P.; Kantak, Kathleen M.

2015-01-01

Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar-Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d-Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model. PMID:26467602

5-Hydroxytryptamine (serotonin)2A receptors in rat anterior cingulate cortex mediate the discriminative stimulus properties of d-lysergic acid diethylamide.

PubMed

Gresch, Paul J; Barrett, Robert J; Sanders-Bush, Elaine; Smith, Randy L

2007-02-01

d-Lysergic acid diethylamide (LSD), an indoleamine hallucinogen, produces profound alterations in mood, thought, and perception in humans. The brain site(s) that mediates the effects of LSD is currently unknown. In this study, we combine the drug discrimination paradigm with intracerebral microinjections to investigate the anatomical localization of the discriminative stimulus of LSD in rats. Based on our previous findings, we targeted the anterior cingulate cortex (ACC) to test its involvement in mediating the discriminative stimulus properties of LSD. Rats were trained to discriminate systemically administered LSD (0.085 mg/kg s.c.) from saline. Following acquisition of the discrimination, bilateral cannulae were implanted into the ACC (AP, +1.2 mm; ML, +/-1.0 mm; DV, -2.0 mm relative to bregma). Rats were tested for their ability to discriminate varying doses of locally infused LSD (0.1875, 0.375, and 0.75 microg/side) or artificial cerebrospinal fluid (n = 3-7). LSD locally infused into ACC dose-dependently substituted for systemically administered LSD, with 0.75 microg/side LSD substituting completely (89% correct). Systemic administration of the selective 5-hydroxytryptamine (serotonin) (5-HT)(2A) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907; 0.4 mg/kg) blocked the discriminative cue of LSD (0.375 microg/side) infused into ACC (from 68 to 16% drug lever responding). Furthermore, M100907 (0.5 microg/microl/side) locally infused into ACC completely blocked the stimulus effects of systemic LSD (0.04 mg/kg; from 80 to 12% on the LSD lever). Taken together, these data indicate that 5-HT(2A) receptors in the ACC are a primary target mediating the discriminative stimulus properties of LSD.

Effects of adolescent exposure to methylmercury and d-amphetamine on reversal learning and an extradimensional shift in male mice.

PubMed

Boomhower, Steven R; Newland, M Christopher

2017-04-01

Adolescence is associated with the continued maturation of dopamine neurotransmission and is implicated in the etiology of many psychiatric illnesses. Adolescent exposure to neurotoxicants that distort dopamine neurotransmission, such as methylmercury (MeHg), may modify the effects of chronic d -amphetamine ( d -AMP) administration on reversal learning and attentional-set shifting. Male C57Bl/6n mice were randomly assigned to two MeHg-exposure groups (0 ppm and 3 ppm) and two d -AMP-exposure groups (saline and 1 mg/kg/day), producing four treatment groups (n = 10-12/group): control, MeHg , d -AMP, and MeHg + d -AMP. MeHg exposure (via drinking water) spanned postnatal days 21-59 (the murine adolescent period), and once daily intraperitoneal injections of d -AMP or saline spanned postnatal days 28-42. As adults, mice were trained on a spatial-discrimination-reversal (SDR) task in which the spatial location of a lever press predicted reinforcement. Following 2 SDRs, a visual-discrimination task (extradimensional shift) was instated in which the presence of a stimulus light above a lever predicted reinforcement. Responding was modeled using a logistic function, which estimated the rate (slope) of a behavioral transition and trials required to complete half a transition (half-max). MeHg, d -AMP, and MeHg + d -AMP exposure increased estimates of half-max on the second reversal. MeHg exposure increased half-max and decreased the slope term following the extradimensional shift, but these effects did not occur following MeHg + d -AMP exposure. MeHg + d -AMP exposure produced more perseverative errors and omissions following a reversal. Adolescent exposure to MeHg can modify the behavioral effects of chronic d -AMP administration. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Behavioral predictors of alcohol drinking in a neurodevelopmental rat model of schizophrenia and co-occurring alcohol use disorder.

PubMed

Khokhar, Jibran Y; Todd, Travis P

2018-04-01

Alcohol use disorder commonly occurs in patients with schizophrenia and contributes greatly to its morbidity. Unfortunately, the neural and behavioral underpinnings of alcohol drinking in these patients are not well understood. In order to begin to understand the cognitive and reward-related changes that may contribute to alcohol drinking, this study was designed to address: 1) latent inhibition; 2) conditioning; and 3) extinction of autoshaping in a neurodevelopmental rat model with relevance to co-occurring schizophrenia and alcohol use disorders, the neonatal ventral hippocampal lesioned (NVHL) rat. NVHL lesions (or sham surgeries) were performed on post-natal day 7 (PND7) and animals were given brief exposure to alcohol during adolescent (PND 28-42). Latent inhibition of autoshaping, conditioning and extinction were assessed between PND 72-90. On PND90 animals were given alcohol again and allowed to establish stable drinking. Latent inhibition of autoshaping was found to be prolonged in the NVHL rats; the NVHL rats pre-exposed to the lever stimulus were slower to acquire autoshaping than sham pre-exposed rats. NVHL rats that were not pre-exposed to the lever stimulus did not differ during conditioning, but were slower to extinguish conditioned responding compared to sham controls. Finally, the NVHL rats from both groups drank significantly more alcohol than sham rats, and the extent of latent inhibition predicted future alcohol intake in the pre-exposed animals. These findings suggest that the latent inhibition of autoshaping procedure can be used to model cognitive- and reward-related dysfunctions in schizophrenia, and these dysfunctions may contribute to the development of co-occurring alcohol use. Copyright © 2017 Elsevier B.V. All rights reserved.

The adenosine A2A antagonist MSX-3 reverses the effort-related effects of dopamine blockade: differential interaction with D1 and D2 family antagonists.

PubMed

Worden, Lila T; Shahriari, Mona; Farrar, Andrew M; Sink, Kelly S; Hockemeyer, Jörg; Müller, Christa E; Salamone, John D

2009-04-01

Brain dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired DA transmission reallocate their behavior away from food-seeking behaviors that have high response requirements, and instead select less effortful alternatives. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related choice behavior, emerging evidence demonstrates a role for adenosine A(2A) receptors. Adenosine A(2A) receptor antagonism has been shown to reverse the effects of DA antagonism. The present experiments were conducted to determine if this effect was dependent upon the subtype of DA receptor that was antagonized to produce the changes in effort-related choice. The adenosine A(2A) receptor antagonist MSX-3 (0.5-2.0 mg/kg IP) was assessed for its ability to reverse the effects of the D1 family antagonist SCH39166 (ecopipam; 0.2 mg/kg IP) and the D2 family antagonist eticlopride (0.08 mg/kg IP), using a concurrent lever pressing/chow feeding procedure. MSX-3 produced a substantial dose-related reversal of the effects of eticlopride on lever pressing and chow intake. At the highest dose of MSX-3, there was a complete reversal of the effects of eticlopride on lever pressing. In contrast, MSX-3 produced only a minimal attenuation of the effects of SCH39166, as measured by regression and effect size analyses. The greater ability of MSX-3 to reverse the effects of D2 vs. D1 blockade may be related to the colocalization of D2 and adenosine A(2A) receptors on the same population of striatal neurons.

Validation of operant social motivation paradigms using BTBR T+tf/J and C57BL/6J inbred mouse strains

PubMed Central

Martin, Loren; Sample, Hannah; Gregg, Michael; Wood, Caleb

2014-01-01

Background As purported causal factors are identified for autism spectrum disorder (ASD), new assays are needed to better phenotype animal models designed to explore these factors. With recent evidence suggesting that deficits in social motivation are at the core of ASD behavior, the development of quantitative measures of social motivation is particularly important. The goal of our study was to develop and validate novel assays to quantitatively measure social motivation in mice. Methods In order to test the validity of our paradigms, we compared the BTBR strain, with documented social deficits, to the prosocial C57BL/6J strain. Two novel conditioning paradigms were developed that allowed the test mouse to control access to a social partner. In the social motivation task, the test mice lever pressed for a social reward. The reward contingency was set on a progressive ratio of reinforcement and the number of lever presses achieved in the final trial of a testing session (breakpoint) was used as an index of social motivation. In the valence comparison task, motivation for a food reward was compared to a social reward. We also explored activity, social affiliation, and preference for social novelty through a series of tasks using an ANY-Maze video-tracking system in an open-field arena. Results BTBR mice had significantly lower breakpoints in the social motivation paradigm than C57BL/6J mice. However, the valence comparison task revealed that BTBR mice also made significantly fewer lever presses for a food reward. Conclusions The results of the conditioning paradigms suggest that the BTBR strain has an overall deficit in motivated behavior. Furthermore, the results of the open-field observations may suggest that social differences in the BTBR strain are anxiety induced. PMID:25328850

Validation of operant social motivation paradigms using BTBR T+tf/J and C57BL/6J inbred mouse strains.

PubMed

Martin, Loren; Sample, Hannah; Gregg, Michael; Wood, Caleb

2014-09-01

As purported causal factors are identified for autism spectrum disorder (ASD), new assays are needed to better phenotype animal models designed to explore these factors. With recent evidence suggesting that deficits in social motivation are at the core of ASD behavior, the development of quantitative measures of social motivation is particularly important. The goal of our study was to develop and validate novel assays to quantitatively measure social motivation in mice. In order to test the validity of our paradigms, we compared the BTBR strain, with documented social deficits, to the prosocial C57BL/6J strain. Two novel conditioning paradigms were developed that allowed the test mouse to control access to a social partner. In the social motivation task, the test mice lever pressed for a social reward. The reward contingency was set on a progressive ratio of reinforcement and the number of lever presses achieved in the final trial of a testing session (breakpoint) was used as an index of social motivation. In the valence comparison task, motivation for a food reward was compared to a social reward. We also explored activity, social affiliation, and preference for social novelty through a series of tasks using an ANY-Maze video-tracking system in an open-field arena. BTBR mice had significantly lower breakpoints in the social motivation paradigm than C57BL/6J mice. However, the valence comparison task revealed that BTBR mice also made significantly fewer lever presses for a food reward. The results of the conditioning paradigms suggest that the BTBR strain has an overall deficit in motivated behavior. Furthermore, the results of the open-field observations may suggest that social differences in the BTBR strain are anxiety induced.

Dorsolateral neostriatum contribution to incentive salience: opioid or dopamine stimulation makes one reward cue more motivationally attractive than another.

PubMed

DiFeliceantonio, Alexandra G; Berridge, Kent C

2016-05-01

Pavlovian cues for rewards can become attractive incentives: approached and 'wanted' as the rewards themselves. The motivational attractiveness of a previously learned cue is not fixed, but can be dynamically amplified during re-encounter by simultaneous activation of brain limbic circuitry. Here it was reported that opioid or dopamine microinjections in the dorsolateral quadrant of the neostriatum (DLS) of rats selectively amplify attraction toward a previously learned Pavlovian cue in an individualized fashion, at the expense of a competing cue. In an autoshaping (sign-tracking vs. goal-tracking) paradigm, microinjection of the mu opioid receptor agonist (DAMGO) or dopamine indirect agonist (amphetamine) in the DLS of sign-tracker individuals selectively enhanced their sign-tracking attraction toward the reward-predictive lever cue. By contrast, DAMGO or amphetamine in the DLS of goal-trackers selectively enhanced prepotent attraction toward the reward-proximal cue of sucrose dish. Amphetamine also enhanced goal-tracking in some sign-tracker individuals (if they ever defected to the dish even once). That DLS enhancement of cue attraction was due to stronger motivation, not stronger habits, was suggested by: (i) sign-trackers flexibly followed their cue to a new location when the lever was suddenly moved after DLS DAMGO microinjection; and (ii) DAMGO in the DLS also made sign-trackers work harder on a new instrumental nose-poke response required to earn presentations of their Pavlovian lever cue (instrumental conditioned reinforcement). Altogether, the current results suggest that DLS circuitry can enhance the incentive salience of a Pavlovian reward cue, selectively making that cue a stronger motivational magnet. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment.

PubMed

Orsini, Caitlin A; Trotta, Rose T; Bizon, Jennifer L; Setlow, Barry

2015-01-28

Several neuropsychiatric disorders are associated with abnormal decision-making involving risk of punishment, but the neural basis of this association remains poorly understood. Altered activity in brain systems including the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) can accompany these same disorders, and these structures are implicated in some forms of decision-making. The current study investigated the role of the BLA and OFC in decision-making under risk of explicit punishment. Rats were trained in the risky decision-making task (RDT), in which they chose between two levers, one that delivered a small safe reward, and the other that delivered a large reward accompanied by varying risks of footshock punishment. Following training, they received sham or neurotoxic lesions of BLA or OFC, followed by RDT retesting. BLA lesions increased choice of the large risky reward (greater risk-taking) compared to both prelesion performance and sham controls. When reward magnitudes were equated, both BLA lesion and control groups shifted their choice to the safe (no shock) reward lever, indicating that the lesions did not impair punishment sensitivity. In contrast to BLA lesions, OFC lesions significantly decreased risk-taking compared with sham controls, but did not impair discrimination between different reward magnitudes or alter baseline levels of anxiety. Finally, neither lesion significantly affected food-motivated lever pressing under various fixed ratio schedules, indicating that lesion-induced alterations in risk-taking were not secondary to changes in appetitive motivation. Together, these findings indicate distinct roles for the BLA and OFC in decision-making under risk of explicit punishment. Copyright © 2015 the authors 0270-6474/15/351368-12$15.00/0.

Increased ethanol self-administration after a period of imposed ethanol deprivation in rats trained in a limited access paradigm.

PubMed

Heyser, C J; Schulteis, G; Koob, G F

1997-08-01

A predominant feature in human alcohol abuse is the reported desire or "craving" to consume ethanol along with frequent episodes of drinking after periods of abstinence. These and other factors may be responsible for relapse to uncontrolled ethanol drinking. When relapse occurs after a period of abstinence, ethanol drinking has been shown to be temporarily increased. Two aspects of drug dependence could contribute to these increases. One may be the development of a need state; the other may involve changes in the perception of the positive reinforcing effects of ethanol when reinforcer access is limited. To investigate this phenomenon further, the present study was conducted to examine in nondependent rats the effect of forced time-off on oral ethanol self-administration in a limited access paradigm (30 min/day). Male Wistar rats were trained to respond for ethanol (10% w/v) or water in a two-lever, free-choice condition using a saccharin fading procedure. After the establishment of stable baseline responding for ethanol, various ethanol deprivation periods (3, 5, 7, 14, or 28 days) were imposed, during which no ethanol was available. Responding for ethanol increased as a function of the duration of the deprivation period when compared with baseline levels. This increase was temporary and returned to baseline levels within 2 to 3 days. Given that the shortest time-off period was 5 days and the rats showed no signs of withdrawal, this transient increase in ethanol responding does not seem to be related to the manifestation of dependence and withdrawal, and may be related to changes in ethanol's reinforcement properties. These results with rats may provide a useful tool to elucidate mechanisms underlying human alcohol seeking behavior and relapse.

Effect of yohimbine on reinstatement of operant responding in rats is dependent on cue contingency but not food reward history.

PubMed

Chen, Yu-Wei; Fiscella, Kimberly A; Bacharach, Samuel Z; Tanda, Gianluigi; Shaham, Yavin; Calu, Donna J

2015-07-01

Yohimbine is an alpha-2 adrenoceptor antagonist that has been used in numerous studies as a pharmacological stressor in rodents, monkeys and humans. Recently, yohimbine has become the most common stress manipulation in studies on reinstatement of drug and food seeking. However, the wide range of conditions under which yohimbine promotes reward seeking is significantly greater than that of stressors like intermittent footshock. Here, we addressed two fundamental questions regarding yohimbine's effect on reinstatement of reward seeking: (1) whether the drug's effect on operant responding is dependent on previous reward history or cue contingency, and (2) whether yohimbine is aversive or rewarding under conditions typically used in reinstatement studies. We also used in vivo microdialysis to determine yohimbine's effect on dopamine levels in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). We found that the magnitude of yohimbine-induced (0.5, 1.0, 2.0 mg/kg) operant responding during the reinstatement tests was critically dependent on the contingency between lever pressing and discrete tone-light cue delivery but not the previous history with food reward during training. We also found that yohimbine (2 mg/kg) did not cause conditioned place aversion. Finally, we found that yohimbine modestly increased dopamine levels in mPFC but not NAc. Results suggest that yohimbine's effects on operant responding in reinstatement studies are likely independent of the history of contingent self-administration of food or drug rewards and may not be related to the commonly assumed stress-like effects of yohimbine. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Cocaine influences alcohol-seeking behavior and relapse drinking in alcohol-preferring (P) rats.

PubMed

Hauser, Sheketha R; Wilden, Jessica A; Deehan, Gerald A; McBride, William J; Rodd, Zachary A

2014-10-01

The results of several studies suggest that there may be common neurocircuits regulating drug-seeking behaviors. Common biological pathways regulating drug-seeking would explain the phenomenon that seeking for 1 drug can be enhanced by exposure to another drug of abuse. The objective of this study was to assess the time course effects of acute cocaine administration on ethanol (EtOH) seeking and relapse. Alcohol-preferring (P) rats were allowed to self-administer 15% EtOH and water. EtOH-seeking was assessed through the use of the Pavlovian spontaneous recovery (PSR) model, while EtOH-relapse drinking was assessed through the use of the alcohol-deprivation effect. Cocaine (0, 1, or 10 mg/kg), injected immediately, 30 minutes, or 4 hours prior to the first PSR testing session, dose-dependently increased responding on the EtOH lever compared to extinction responses and responding by saline controls. Under relapse conditions, cocaine given immediately prior to the relapse session had no effect (1 mg/kg) or reduced responding (10 mg/kg). In contrast, cocaine given 4 hours prior to the relapse session markedly enhanced EtOH responding compared to saline. The enhanced expression of EtOH-seeking and EtOH-relapse behaviors may be a result of a priming effect of cocaine on neuronal circuits mediating these behaviors. The effect of cocaine on EtOH-relapse drinking is indicative of the complex interactions that can occur between drugs of abuse; production of conflicting behaviors (immediate), and priming of relapse/seeking (4-hour delay). Copyright © 2014 by the Research Society on Alcoholism.

Pump control system for windmills

DOEpatents

Avery, Don E.

1983-01-01

A windmill control system having lever means, for varying length of stroke of the pump piston, and a control means, responsive to the velocity of the wind to operate the lever means to vary the length of stroke and hence the effective displacement of the pump in accordance with available wind energy, with the control means having a sensing member separate from the windmill disposed in the wind and displaceable thereby in accordance with wind velocity.

Tactile Sensors for Palm-Size Crawling Robots

DTIC Science & Technology

2014-05-01

lamination and laser cutting . For the sensor array discussed in this report, the hairs have an average normal sensitivity of approximately 0.8 grams/hair, but...Adhesive (M) Hair Mounting Layer. For visualization purposes, layers I and M are shown with laser - cut features that are actually formed after...The levers are then partially freed from the structure via laser - cutting . The levers are left partly connected at this point so that the hairs (L) can

Mi Segundo Libro de Maquinas Simples: Las Palancas. Escuela Intermedia Grados 7, 8 y 9 (My Second Book of Simple Machines: Levers. Intermediate School Grades 7, 8, and 9).

ERIC Educational Resources Information Center

Alvarado, Patricio R.; Montalvo, Luis

This is the second book in a five-book physical science series on simple machines. The books are designed for Spanish-speaking junior high school students. By suggesting experiments and posing questions concerning drawings in the book which illustrate the scientific principles, this book explains the workings of three types of levers. Resistance…

Technical Writing: Its Importance in the Engineering Profession and Its Place in Engineering Curricula - A Survey of the Experience and Opinions of Prominent Engineers.

DTIC Science & Technology

1975-08-09

others, both orally and in writing. - Richard C. LeVere Johns - Manville Denver, Colorado 18 p»w>.^wammMiim<^*ji!wi»i; w mra’i&JifAt. 1...communicate with others, both orally and in writing. Richard C. LeVere Johns - Manville Denver, Colorado Research - research is not con^lete until the

Geometrical analysis of an optical fiber bundle displacement sensor

NASA Astrophysics Data System (ADS)

Shimamoto, Atsushi; Tanaka, Kohichi

1996-12-01

The performance of a multifiber optical lever was geometrically analyzed by extending the Cook and Hamm model [Appl. Opt. 34, 5854-5860 (1995)] for a basic seven-fiber optical lever. The generalized relationships between sensitivity and the displacement detection limit to the fiber core radius, illumination irradiance, and coupling angle were obtained by analyses of three various types of light source, i.e., a parallel beam light source, an infinite plane light source, and a point light source. The analysis of the point light source was confirmed by a measurement that used the light source of a light-emitting diode. The sensitivity of the fiber-optic lever is inversely proportional to the fiber core radius, whereas the receiving light power is proportional to the number of illuminating and receiving fibers. Thus, the bundling of the finer fiber with the larger number of illuminating and receiving fibers is more effective for improving sensitivity and the displacement detection limit.

Mounting clips for panel installation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cavieres, Andres; Al-Haddad, Tristan; Goodman, Joseph

2017-02-14

An exemplary mounting clip for removably attaching panels to a supporting structure comprises a base, spring locking clips, a lateral flange, a lever flange, and a spring bonding pad. The spring locking clips extend upwardly from the base. The lateral flange extends upwardly from a first side of the base. The lateral flange comprises a slot having an opening configured to receive at least a portion of one of the one or more panels. The lever flange extends outwardly from the lateral flange. The spring bonding flange extends downwardly from the lever flange. At least a portion of the firstmore » spring bonding flange comprises a serrated edge for gouging at least a portion of the one or more panels when the one or more panels are attached to the mounting clip to electrically and mechanically couple the one or more panels to the mounting clip.« less

Calibration Procedures in Mid Format Camera Setups

NASA Astrophysics Data System (ADS)

Pivnicka, F.; Kemper, G.; Geissler, S.

2012-07-01

A growing number of mid-format cameras are used for aerial surveying projects. To achieve a reliable and geometrically precise result also in the photogrammetric workflow, awareness on the sensitive parts is important. The use of direct referencing systems (GPS/IMU), the mounting on a stabilizing camera platform and the specific values of the mid format camera make a professional setup with various calibration and misalignment operations necessary. An important part is to have a proper camera calibration. Using aerial images over a well designed test field with 3D structures and/or different flight altitudes enable the determination of calibration values in Bingo software. It will be demonstrated how such a calibration can be performed. The direct referencing device must be mounted in a solid and reliable way to the camera. Beside the mechanical work especially in mounting the camera beside the IMU, 2 lever arms have to be measured in mm accuracy. Important are the lever arms from the GPS Antenna to the IMU's calibrated centre and also the lever arm from the IMU centre to the Camera projection centre. In fact, the measurement with a total station is not a difficult task but the definition of the right centres and the need for using rotation matrices can cause serious accuracy problems. The benefit of small and medium format cameras is that also smaller aircrafts can be used. Like that, a gyro bases stabilized platform is recommended. This causes, that the IMU must be mounted beside the camera on the stabilizer. The advantage is, that the IMU can be used to control the platform, the problematic thing is, that the IMU to GPS antenna lever arm is floating. In fact we have to deal with an additional data stream, the values of the movement of the stabiliser to correct the floating lever arm distances. If the post-processing of the GPS-IMU data by taking the floating levers into account, delivers an expected result, the lever arms between IMU and camera can be applied. However, there is a misalignment (bore side angle) that must be evaluated by photogrammetric process using advanced tools e.g. in Bingo. Once, all these parameters have been determined, the system is capable for projects without or with only a few ground control points. But which effect has the photogrammetric process when directly applying the achieved direct orientation values compared with an AT based on a proper tiepoint matching? The paper aims to show the steps to be done by potential users and gives a kind of quality estimation about the importance and quality influence of the various calibration and adjustment steps.

Mutating the converter-relay interface of Drosophila myosin perturbs ATPase activity, actin motility, myofibril stability and flight ability.

PubMed

Kronert, William A; Melkani, Girish C; Melkani, Anju; Bernstein, Sanford I

2010-05-21

We used an integrative approach to probe the significance of the interaction between the relay loop and converter domain of the myosin molecular motor from Drosophila melanogaster indirect flight muscle. During the myosin mechanochemical cycle, ATP-induced twisting of the relay loop is hypothesized to reposition the converter, resulting in cocking of the contiguous lever arm into the pre-power stroke configuration. The subsequent movement of the lever arm through its power stroke generates muscle contraction by causing myosin heads to pull on actin filaments. We generated a transgenic line expressing myosin with a mutation in the converter domain (R759E) at a site of relay loop interaction. Molecular modeling suggests that the interface between the relay loop and converter domain of R759E myosin would be significantly disrupted during the mechanochemical cycle. The mutation depressed calcium as well as basal and actin-activated MgATPase (V(max)) by approximately 60% compared to wild-type myosin, but there is no change in apparent actin affinity (K(m)). While ATP or AMP-PNP (adenylyl-imidodiphosphate) binding to wild-type myosin subfragment-1 enhanced tryptophan fluorescence by approximately 15% or approximately 8%, respectively, enhancement does not occur in the mutant. This suggests that the mutation reduces lever arm movement. The mutation decreases in vitro motility of actin filaments by approximately 35%. Mutant pupal indirect flight muscles display normal myofibril assembly, myofibril shape, and double-hexagonal arrangement of thick and thin filaments. Two-day-old fibers have occasional "cracking" of the crystal-like array of myofilaments. Fibers from 1-week-old adults show more severe cracking and frayed myofibrils with some disruption of the myofilament lattice. Flight ability is reduced in 2-day-old flies compared to wild-type controls, with no upward mobility but some horizontal flight. In 1-week-old adults, flight capability is lost. Thus, altered myosin function permits myofibril assembly, but results in a progressive disruption of the myofilament lattice and flight ability. We conclude that R759 in the myosin converter domain is essential for normal ATPase activity, in vitro motility and locomotion. Our results provide the first mutational evidence that intramolecular signaling between the relay loop and converter domain is critical for myosin function both in vitro and in muscle. (c) 2010 Elsevier Ltd. All rights reserved.

Method of making an ion-implanted planar-buried-heterostructure diode laser

DOEpatents

Brennan, Thomas M.; Hammons, Burrell E.; Myers, David R.; Vawter, Gregory A.

1992-01-01

Planar-buried-heterostructure, graded-index, separate-confinement-heterostructure semiconductor diode laser 10 includes a single quantum well or multi-quantum well active stripe 12 disposed between a p-type compositionally graded Group III-V cladding lever 14 and an n-type compositionally graded Group III-V cladding layer 16. The laser 10 includes an iion implanted n-type region 28 within the p-type cladding layer 14 and further includes an ion implanted p-type region 26 within the n-type cladding layer 16. The ion implanted regions are disposed for defining a lateral extent of the active stripe.

The Potential Risks and Future Impact of a Large Leverett Glacier Crevasse along the South Pole Traverse (SPoT)

DTIC Science & Technology

2017-10-01

agricultural tractors used on SPoT (Case Corporation and Caterpillar). (Adapted from Lever and Thur 2014.) ................. 2 2 Map showing the 1600...traversed for the first time in 2005 as a proof-of-concept, using a combination of several commercial rubber-tracked agricultural tractors (Caterpillar...traverse route. Inset shows two rubber-tracked, agricultural tractors used on SPoT (Case Corporation and Caterpillar). (Adapted from Lever and Thur 2014