Khor, Yee Min; Soga, Tomoko; Parhar, Ishwar S
The early-life stress has critical impact on brain development which can lead to long-term effects on brain functions during adulthood. It has been reported that caffeine possesses a protective effect in neurodegenerative diseases. Thus, this study investigates the potential of caffeine to protect brain functions from adverse effects due to stress exposure during early-life development in the male zebrafish. In the first part of this study, synthetic glucocorticoid, dexamethasone (DEX) (2-200 mg/L for 24 h) was used to induce stress effects in the zebrafish larvae from 4 to 5 days post-fertilisation (dpf) and the effect of DEX administration on zebrafish larvae on anxiety-like behaviour during adulthood in novel tank test was investigated. Next, the possible protective effect of caffeine pre-treatment (5-50 mg/L for 24 h from 3 to 4dpf) before DEX administration was studied. DEX-treated adult male zebrafish showed higher anxiety levels in behavioural tests, as seen in longer latency to enter the top part of the tank, lower transition numbers between the top and bottom parts with more time spent at the bottom and lesser time spent at the top and lower distance travelled at top part. The effect of DEX on anxiety-like behaviour was dose-dependent. Importantly, adult male zebrafish pre-treated with caffeine before DEX treatment did not show any anxiety-like behaviour. These results show that exposure to stress during early-life leads to anxiety-like behaviour in the adult male zebrafish but pre-treatment with caffeine protects from stress-induced anxiety.
Modafinil (2-((diphenylmethyl)sulfinyl)acetamide), a selective dopamine and norepinephrine transporter inhibitor, is most commonly prescribed for narcolepsy but has gained recent interest for treating a variety of disorders. Zebrafish (Danio rerio) are becoming a model of choice for pharmacological and behavioural research. To investigate the behavioural effects of modafinil on anxiety, we administered doses of 0, 2, 20, and 200 mg/L for 30 minutes then tested zebrafish in the novel approach test. In this test, the fish was placed into a circular arena with a novel object in the center and motion-tracking software was used to quantify the time the fish spent in the outer area of the arena (thigmotaxis zone), middle third of the arena (transition zone) and center of the arena, as well as total distance traveled, immobility and meandering. Modafinil caused a decrease in time spent in the thigmotaxis zone and increased time spent in the transition zone across all doses. Modafinil did not significantly alter the time spent in the center zone (near the novel object), the distance moved, meandering, or the duration of time spent immobile. We also validated this test as a measure of anxiety with the administration of ethanol (1%) which decreased time spent in the thigmotaxis zone and increased time spent in the transition zone. These results suggest that modafinil decreases anxiety-like behaviour in zebrafish. PMID:28229024
Bacqué-Cazenave, Julien; Cattaert, Daniel; Delbecque, Jean-Paul; Fossat, Pascal
Social interactions leading to dominance hierarchies often elicit psychological disorders in mammals including harassment and anxiety. Here, we demonstrate that this sequence also occurs in an invertebrate, the crayfish Procambarus clarkii. When placed in the restricted space of an aquarium, crayfish dyads generally fight until one of the opponents suddenly escapes, thereafter clearly expressing a submissive behaviour. Nevertheless, the winner frequently keeps on displaying excessive aggressive acts, having deleterious consequences in losers and interpreted as harassment behaviour. We indeed observed that, contrary to winners, losers expressed anxiety-like behaviour (ALB) in correlation with the stress intensity they suffered during the harassment period mainly. Injections of an anxiolytic abolished ALB, confirming its homology with anxiety. A serotonin (5-HT) antagonist had the same effect, suggesting a role for 5-HT, whose brain concentrations increased much more in losers than in winners. Our findings suggest that the bases of harassment and of its anxiogenic consequences have emerged very early during evolution, and emphasize crayfish as an unexpected but potentially fruitful model for the study of these social disorders. PMID:28045136
Johnson, Adrian; Hamilton, Trevor James
Modafinil (2-((diphenylmethyl)sulfinyl)acetamide), a selective dopamine and norepinephrine transporter inhibitor, is most commonly prescribed for narcolepsy but has gained recent interest for treating a variety of disorders. Zebrafish (Danio rerio) are becoming a model of choice for pharmacological and behavioural research. To investigate the behavioural effects of modafinil on anxiety, we administered doses of 0, 2, 20, and 200 mg/L for 30 minutes then tested zebrafish in the novel approach test. In this test, the fish was placed into a circular arena with a novel object in the center and motion-tracking software was used to quantify the time the fish spent in the outer area of the arena (thigmotaxis zone), middle third of the arena (transition zone) and center of the arena, as well as total distance traveled, immobility and meandering. Modafinil caused a decrease in time spent in the thigmotaxis zone and increased time spent in the transition zone across all doses. Modafinil did not significantly alter the time spent in the center zone (near the novel object), the distance moved, meandering, or the duration of time spent immobile. We also validated this test as a measure of anxiety with the administration of ethanol (1%) which decreased time spent in the thigmotaxis zone and increased time spent in the transition zone. These results suggest that modafinil decreases anxiety-like behaviour in zebrafish.
Leret, M Luisa; Millán, Jose Antonio San; Antonio, M Teresa
The present study examines the effects of early simultaneous exposure to low level of lead and cadmium on anxiety-like behaviour in the rat, and on monoamine levels in the hypothalamus and hippocampus at weaning and adult animals. Rats were intoxicated with cadmium acetate (10 mg/l) and lead acetate (300 mg/l) in drinking water from the beginning of pregnancy until weaning. Maternal co-exposure to lead and cadmium produced mainly alterations in dopaminergic and serotoninergic systems of hippocampus in both age studied, while noradrenaline content in hypothalamus and hippocampus remained unchanged at 75 days of age. The intoxicated rats showed an increased on indices of anxiety on the elevated plus-maze. These long-term changes in anxiety-like behaviour can be related to dopaminergic and serotoninergic alterations detected in hippocampus.
Baiamonte, Matteo; Parker, Matthew O.; Vinson, Gavin P.; Brennan, Caroline H.
In zebrafish developmentally exposed to ambient ethanol (20mM-50mM) 1–9 days post fertilization (dpf), the cortisol response to stress has been shown to be significantly attenuated in larvae, juveniles and 6 month old adults. These data are somewhat at variance with similar studies in mammals, which often show heightened stress responses. To test whether these cortisol data correlate with behavioural changes in treated animals, anxiety-like behaviour of zebrafish larvae (9dpf and 10dpf) and juveniles (23dpf) was tested in locomotor assays designed to this end. In open field tests treated animals were more exploratory, spending significantly less time at the periphery of the arena. Behavioural effects of developmental exposure to ethanol were sustained in 6-month-old adults, as judged by assessment of thigmotaxis, novel tank diving and scototaxis. Like larvae and juveniles, developmentally treated adults were generally more exploratory, and spent less time at the periphery of the arena in thigmotaxis tests, less time at the bottom of the tank in the novel tank diving tests, and less time in the dark area in scototaxis tests. The conclusion that ethanol-exposed animals showed less anxiety-like behaviour was validated by comparison with the effects of diazepam treatment, which in thigmotaxis and novel tank diving tests had similar effects to ethanol pretreatment. There is thus a possible link between the hypophyseal-pituitary-interrenal axis and the behavioural actions of developmental ethanol exposure. The mechanisms require further elucidation. PMID:26862749
Magalhães, Ana; Valentim, Ana; Venâncio, Carlos; Pereira, Mariana; Melo, Pedro; Summavielle, Teresa; Antunes, Luis
Ketamine administration has been associated with controversial behavioural impairments and psychotic episodes. Even though ketamine alone and in combination with midazolam or dexmedetomidine are frequently used in laboratory animals, the side-effects of such protocols are not well known. Therefore, our aim was to evaluate the effects of ketamine alone and in combination with midazolam or dexmedetomidine on emotional reactivity, as well as the effects on learning and memory in adult rats at least 48 h after anaesthesia. The evaluation of the potential influence of 100 mg/kg ketamine administered alone and in combination with midazolam (5 mg/kg), or dexmedetomidine (0.25 mg/kg) on spatial learning and recognition memory was studied in adult Wistar rats using the radial maze as well as object recognition and location tests. The influence of these combinations on emotional reactivity was investigated using the new exploration test and the elevated plus maze. Results showed that ketamine alone or in combination with midazolam or dexmedetomidine affected neither spatial and recognition memory, nor emotional reactivity. These results reinforce the safe clinical use of ketamine and its combinations in rats in a research context since the administration of these anaesthetic combinations did not produce significant changes with regard to spatial and recognition memory or emotional reactivity. Furthermore, these results indicate that the quality of scientific data produced in adult rat neurobehavioural research is not jeopardized by the use of these anaesthetic protocols.
Hamilton, Trevor James; Kwan, Garfield T.; Gallup, Joshua; Tresguerres, Martin
Aggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac®, followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab. PMID:26806870
Hamilton, Trevor James; Kwan, Garfield T; Gallup, Joshua; Tresguerres, Martin
Aggression and responsiveness to noxious stimuli are adaptable traits that are ubiquitous throughout the animal kingdom. Like vertebrate animals, some invertebrates have been shown to exhibit anxiety-like behaviour and altered levels of aggression that are modulated by the neurotransmitter serotonin. To investigate whether this influence of serotonin is conserved in crabs and whether these behaviours are sensitive to human antidepressant drugs; the striped shore crab, Pachygrapsus crassipes, was studied using anxiety (light/dark test) and aggression (mirror test) paradigms. Crabs were individually exposed to acute doses of the selective serotonin reuptake inhibitor, fluoxetine (5 or 25 mg/L), commonly known as Prozac®, followed by behavioural testing. The high dose of fluoxetine significantly decreased anxiety-like behaviour but had no impact on mobility or aggression. These results suggest that anxiety-like behaviour is more sensitive to modulation of serotonin than is aggressiveness in the shore crab.
Bach, Dominik R
Behavioural inhibition is a key anxiety-like behaviour in rodents and humans, distinct from avoidance of danger, and reduced by anxiolytic drugs. In some situations, it is not clear how behavioural inhibition minimises harm or maximises benefit for the agent, and can even appear counterproductive. Extant explanations of this phenomenon make use of descriptive models but do not provide a formal assessment of its adaptive value. This hampers a better understanding of the neural computations underlying anxiety behaviour. Here, we analyse a standard rodent anxiety model, the operant conflict test. We harvest Bayesian Decision Theory to show that behavioural inhibition normatively arises as cost-minimising strategy in temporally correlated environments. Importantly, only if behavioural inhibition is aimed at minimising cost, it depends on probability and magnitude of threat. Harnessing a virtual computer game, we test model predictions in four experiments with human participants. Humans exhibit behavioural inhibition with a strong linear dependence on threat probability and magnitude. Strikingly, inhibition occurs before motor execution and depends on the virtual environment, thus likely resulting from a neural optimisation process rather than a pre-programmed mechanism. Individual trait anxiety scores predict behavioural inhibition, underlining the validity of this anxiety model. These findings put anxiety behaviour into the context of cost-minimisation and optimal inference, and may ultimately pave the way towards a mechanistic understanding of the neural computations gone awry in human anxiety disorder.
Zlomuzica, Armin; Tress, Oliver; Binder, Sonja; Rovira, Catherine; Willecke, Klaus; Dere, Ekrem
Pelizaeus-Merzbacher-like disease is characterized by impaired psychomotor development, ataxia, progressive spasticity and mental retardation. It is induced by mutations in the gap junction gene GJC2 that encodes for the gap junction protein connexin 47. Mice bearing a human Cx47M283T missense mutation have been generated as a transgenic mouse model of Pelizaeus-Merzbacher-like disease. Homozygous expression of the mutant connexin 47 gene in oligodendrocytes resulted in a complex and variable neuropathologic phenotype, which was associated with impairments in motor coordination in juvenile, but not adult mice. In the present study, we have investigated anxiety-like behaviour and spatial working memory in juvenile (P23) and adult (3-month-old) Cx47M282T mutant mice. Adult Cx47M282T mice were also evaluated in terms of neuromotor functions and in the novel object recognition test. Juvenile Cx47M282T mutant mice exhibited an increase in anxiety-like behaviour in the open field test, but no changes in spatial working memory performance. No significant changes in anxiety-like behaviour, spatial working memory or neuromotor functions were observed in the adult Cx47M282T mutant mice. However, novel object recognition was significantly impaired in adult Cx47M282T mice. Our results suggest that the expression of the human Cx47M282T mutation in the mouse causes changes in anxiety-like behaviour in juvenile and novel object recognition impairments in adult mice. It appears that the distortion of panglial gap junction coupling in white and grey matter tissue in the Cx47M282T mice is associated with a complex age-dependent behavioural phenotype including changes in psychomotor, emotional and memory functions.
Jurek, Benjamin; Slattery, David A; Maloumby, Rodrigue; Hillerer, Katharina; Koszinowski, Sophie; Neumann, Inga D; van den Burg, Erwin H
The c-Raf - MEK1/2 - ERK1/2 mitogen-activated protein kinase (MAPK) intracellular signalling cascade in neurons plays important roles in the control of a variety of behaviours, including social behaviours and anxiety. These roles partially overlap with those described for oxytocin (OXT), and it has been shown that OXT activates the MAPK pathway in the hypothalamus (of male), and hippocampus (of female) rats. Here, by combining behavioural (light/dark box) and biochemical analyses (western blotting), we tested two hypotheses: (i) that OXT is anxiolytic within the hypothalamus of females, and (ii) that this effect, as well as that of lactation-associated anxiolysis, depends on the recruitment of the MAPK pathway. We found that, when injected bilaterally into the hypothalamic paraventricular nucleus (PVN), OXT decreased anxiety-like behaviour in virgins, and that this effect depended on phosphorylation of MEK1/2. MAPK pathway activation in lactation was evident by high phosphorylated (p) MEK1/2 levels, and nuclear translocation of ERK1. The high pMEK1/2 levels were necessary for the anxiolytic phenotype typically observed during lactation. Interestingly, exogenous OXT in lactating rats reduced pMEK1/2 levels without a concomitant effect on anxiety, indicating that OXT receptor activation can lead to recruitment of additional intracellular pathways to modulate MEK activity. Still other pathways could include MEK, but without subsequent activation of ERK, as we did not observe any increase in OXT-induced ERK phosphorylation. Together the results demonstrate that the MAPK pathway, especially MEK1/2, is critically involved in the regulation of anxiety-like behaviour in female rats.
Carrasco, M Carmen; Vidal, Jose; Redolat, Rosa
The aim of this study was to assess the effects of the antidepressant bupropion on anxiety and novelty-seeking in adolescent mice of different ages and adults. Behavioural differences between early adolescent, late adolescent and adult NMRI mice were measured both in the elevated plus-maze and the hole-board tasks following acute administration of bupropion (5, 10, 15, 20mg/kg) or saline. In the plus maze test, early and late adolescent mice treated with bupropion (10, 15mg/kg, respectively) had lower percentages of entries in the open-arms compared to their vehicle controls. Adult mice treated with bupropion did not differ from their vehicle controls. These results suggest that the effect of this drug on anxiety-like behaviour in mice depends on the age, showing adolescents an anxiogenic-like profile. In the hole-board, adolescents showed more elevated levels of novelty-seeking than adults, exhibiting shorter latency to the first head-dip (HD) and a higher number of HD's. Bupropion increases the latency to the first HD and decreases the number of HD's in all age-groups, indicating a decline in exploratory tendency. Findings reveal that the age can modulate the behaviour displayed by mice in both animal models, and that adolescents are more sensitive to bupropion's anxiogenic effects.
Zhang, Cary; Chua, Berenice E; Yang, Annie; Shabanpoor, Fazel; Hossain, Mohammad Akhter; Wade, John D; Rosengren, K Johan; Smith, Craig M; Gundlach, Andrew L
Anxiety disorders are among the most prevalent neuropsychiatric conditions, but their precise aetiology and underlying pathophysiological processes remain poorly understood. In light of putative anatomical and functional interactions of the relaxin-3/RXFP3 system with anxiety-related neural circuits, we assessed the ability of central administration of the RXFP3 agonist, RXFP3-A2, to alter anxiety-like behaviours in adult C57BL/6J mice. We assessed how RXFP3-A2 altered performance in tests measuring rodent anxiety-like behaviour (large open field (LOF), elevated plus maze (EPM), light/dark (L/D) box, social interaction). We examined effects of RXFP3-A2 on low 'basal' anxiety, and on elevated anxiety induced by the anxiogenic benzodiazepine, FG-7142; and explored endogenous relaxin-3/RXFP3 signalling modulation by testing effects of an RXFP3 antagonist, R3(B1-22)R, on these behaviours. Intracerebroventricular (icv) injection of RXFP3-A2 (1 nmol, 15 min pre-test) did not alter anxiety-like behaviour under 'basal' conditions in the LOF, EPM or L/D box, but reduced elevated indices of FG-7142-induced (30 mg/kg, ip) anxiety-like behaviour in the L/D box and a single-chamber social interaction test. Furthermore, R3(B1-22)R (4 nmol, icv, 15 min pre-test) increased anxiety-like behaviour in the EPM (reflected by reduced entries into the open arms), but not consistently in the LOF, L/D box or social interaction tests, suggesting endogenous signaling only weakly participates in regulating 'basal' anxiety-like behaviour, in line with previous studies of relaxin-3 and RXFP3 gene knockout mice. Overall, these data suggest exogenous RXFP3 agonists can reduce elevated (FG-7142-induced) levels of anxiety in mice; data important for gauging how conserved such effects are, with a view to modelling human pathophysiology and the likely therapeutic potential of RXFP3-targeted drugs.
Jangra, Ashok; Lukhi, Manish M; Sulakhiya, Kunjbihari; Baruah, Chandana C; Lahkar, Mangala
Numerous studies have demonstrated that inflammation, oxidative stress and altered level of neurotrophins are involved in the pathogenesis of depressive illness. Mangiferin, a C-glucosylxanthone is abundant in the stem and bark of Mangifera indica L. The compound has been shown to possess antioxidant, anti-inflammatory and immunomodulatory activities. The present study was performed to investigate the effect of mangiferin pretreatment on lipopolysaccharide-induced increased proinflammatory cytokines, oxidative stress and neurobehavioural abnormalities. Mice were challenged with lipopolysaccharide (0.83 mg/kg, i.p.) after 14 days of mangiferin (20 and 40 mg/kg, p.o.) pretreatment. Mangiferin pretreatment significantly ameliorated the anxiety-like behaviour as evident from the results of an elevated plus maze, light-dark box and open field test. Mangiferin pretreatment also improved the anhedonic behaviour as revealed by sucrose preference test and increased social interaction time. It also prevented the lipopolysaccharide-evoked depressive-like effect by reducing the immobility time in forced swim and tail suspension test. Lipopolysaccharide-induced elevated oxidative stress was decreased with mangiferin pretreatment due to its potential to increase reduced glutathione concentration, Superoxide dismutase and catalase activity and decrease lipid peroxidation and nitrite level in the hippocampus as well as in the prefrontal cortex. Mangiferin pretreatment also attenuated neuroinflammation by reducing the interleukin-1 beta (IL-1β) level in hippocampus and prefrontal cortex. In conclusion, our results demonstrated that mangiferin possessed antidepressant and anti-anxiety properties due to its ability to attenuate IL-1β level and oxidative stress evoked by intraperitoneal administration of lipopolysaccharide. Mangiferin may be a potential therapeutic agent for the treatment of depressive and anxiety illness.
Al-Rahbi, Badriya; Zakaria, Rahimah; Othman, Zahiruddin; Hassan, Asma'; Ahmad, Asma Hayati
The present study aims to evaluate the antioxidant and anxiolytic-like effect of Tualang honey in stressed ovariectomized (OVX) rats. The animals were divided into; (i) nonstressed sham-operated control rats, (ii) sham-operated control rats exposed to stress, (iii) nonstressed OVX rats, (iv) OVX rats exposed to stress, (v) OVX rats exposed to stress and treated with 17 β-oestradiol (E2) (20 μg daily, sc), and (vi) OVX rats exposed to stress and treated with Tualang honey (0.2 g/kg body weight, orally). The open field test was used to evaluate the anxiety-like behaviour and ELISA kits were used to measure oxidant/antioxidant status of the brain homogenates. The result showed that anxiety-like behavior was significantly increased in stressed OVX compared to other groups, and administering either E2 or Tualang honey significantly decreased anxiety-like behaviour in stressed OVX rats. The levels of malondialdehyde (MDA) and protein carbonyl (PCO) were significantly decreased while the levels/activities of superoxide dismutase (SOD), glutathione S-transferases (GST), glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly increased in the brain homogenates of treated stressed OVX groups compared to untreated stressed OVX. In conclusion, Tualang honey has protective effects against brain oxidative stress and may be useful alternative anxiolytic agent especially for postmenopausal women. PMID:27379299
Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J
Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior
Richter, S. Helene; Kästner, Niklas; Loddenkemper, Dirk-Heinz; Kaiser, Sylvia; Sachser, Norbert
In mammals, weaning constitutes an important phase in the progression to adulthood. It comprises the termination of suckling and is characterized by several changes in the behaviour of both mother and offspring. Furthermore, numerous studies in rodents have shown that the time point of weaning shapes the behavioural profile of the young. Most of these studies, however, have focused on ‘early weaning’, while relatively little work has been done to study ‘late weaning’ effects. The aim of the present study was therefore to explore behavioural effects of ‘late weaning’, and furthermore to gain insights into modulating effects of weaning age on the consistency of behavioural expressions over time. In total, 25 male and 20 female C57BL/6J mice, weaned after three (W3) or four (W4) weeks of age, were subjected to a series of behavioural paradigms widely used to assess anxiety-like behaviour, exploratory locomotion, and nest building performance. Behavioural testing took place with the mice reaching an age of 20 weeks and was repeated eight weeks later to investigate the stability of behavioural expressions over time. At the group level, W4 mice behaved less anxious and more explorative than W3 animals in the Open Field and Novel Cage, while anxiety-like behaviour on the Elevated Plus Maze was modulated by a weaning-age-by-sex interaction. Furthermore, weaning age shaped the degree of behavioural stability over time in a sex-specific way. While W3 females and W4 males displayed a remarkable degree of behavioural stability over time, no such patterns were observed in W3 males and W4 females. Adding to the existing literature, we could thus confirm that effects of weaning age do indeed exist when prolonging this phase, and were furthermore able to provide first evidence for the impact of weaning age and sex on the consistency of behavioural expressions over time. PMID:27930688
Yasumura, Misato; Yoshida, Tomoyuki; Yamazaki, Maya; Abe, Manabu; Natsume, Rie; Kanno, Kouta; Uemura, Takeshi; Takao, Keizo; Sakimura, Kenji; Kikusui, Takefumi; Miyakawa, Tsuyoshi; Mishina, Masayoshi
IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.
Yasumura, Misato; Yoshida, Tomoyuki; Yamazaki, Maya; Abe, Manabu; Natsume, Rie; Kanno, Kouta; Uemura, Takeshi; Takao, Keizo; Sakimura, Kenji; Kikusui, Takefumi; Miyakawa, Tsuyoshi; Mishina, Masayoshi
IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety. PMID:25312502
Saiyudthong, Somrudee; Pongmayteegul, Sirinun; Marsden, Charles A; Phansuwan-Pujito, Pansiri
Vetiver essential oil (VEO) has been used in aromatherapy for relaxation. This study aimed to investigate the effects of VEO on an anxiety-related behavioural model (the elevated plus-maze, EPM) and immediate-early gene c-fos in amygdala, known to be involved in anxiety. Male Wistar rats were administered diazepam (1 mg/kg i.p.) for 30 min or inhalated with VEO (1%, 2.5% or 5% w/w) for 7 min prior to exposure to the EPM. Then, the effects of 2.5% VEO, the anxiolytic dose, on c-fos expression in amygdala were investigated. The rats given either 2.5% VEO or diazepam exhibited an anxiolytic-like profile in the EPM. VEO and diazepam significantly increased c-fos expression in the lateral division of the central amygdaloid nucleus (CeL). Therefore, the anxiolytic properties of VEO might be associated with altering neuronal activation in CeL. However, future studies are needed to investigate the precise mechanism of action of VEO.
Szakács, Júlia; Csabafi, Krisztina; Lipták, Nándor; Szabó, Gyula
Obestatin is a 23 amino acid-peptide, derived from the same preproghrelin-gene as ghrelin. Obestatin was originally reported as a ghrelin antagonist with anorexigenic activity, but later it was proven to be involved in multiple processes including sleep, memory retention, anxiety, morphine-induced analgesia and withdrawal. In the present study, in male CFLP mice, by using computerised open field (OF) and elevated plus maze (EPM) tests we have investigated the behavioural effects of the acute intracerebroventricular (icv) administration of obestatin alone, and following ghrelin receptor blockage with [d-Lys3]-Growth Hormone Releasing Peptide-6 ([d-Lys3]- GHRP6) or corticotropin-releasing hormone (CRH) receptor 1 antagonism with antalarmin. Plasma corticosterone levels were measured for each treatment group by using chemofluorescent assay. Our results in the EPM test showed that obestatin reduced the percent of time spent in the open arms. The basal locomotor activity (ambulation distance and time, rearing and jumping) was not influenced significantly neither in the obestatin-treated groups, nor in those receiving pre-treatment with antalarmin or [d-Lys3]-GHRP6. The percentage of central ambulation distance however was decreased by obestatin, while the percentage of time spent in the central zone showed a decreasing tendency. The administration of antalarmin or [d-Lys3]-GHRP6 have both reversed the effect of obestatin on central ambulation. Plasma corticosterone levels were elevated by obestatin, which effect was antagonised by the injection of antalarmin. These are the first results to indicate that obestatin exerts anxiogenic-like effect in mice, which might be mediated through ghrelin receptor and CRH activation.
Sivanathan, Shathveekan; Thavartnam, Kabriya; Arif, Shahneen; Elegino, Trisha; McGowan, Patrick O
The consumption of diets high in saturated fats and obesity have been associated with impaired physical and mental health. Previous studies indicate that chronic high fat diet consumption leads to systemic inflammation in humans and non-human animal models. Studies in non-human animals suggest that altered physiological responses to stress are also a consequence of high fat diet consumption. Glucocorticoid signalling mechanisms may link immune and stress-related pathways in the brain, and were shown to be significantly altered in the brains of female rat offspring of mothers exposed to chronic high fat diet during pregnancy and lactation. For adult females, the consequence of chronic high fat diet consumption on these signalling pathways and their relationship to stress-related behaviour is not known. In this study, we examined the effects of chronic consumption of a high fat diet compared to a low fat control diet among adult female Long Evans rats. We found significant differences in weight gain, caloric intake, anxiety-related behaviours, and glucocorticoid-related gene expression over a 10-week exposure period. As expected, rats in the high fat diet group gained the most weight and consumed the greatest number of calories. Rats in the high fat diet group showed significantly greater levels of anxiety-related behaviour in the Light Dark and Open Field tasks compared to rats in the low fat diet group. Rats consuming high fat diet also exhibited reduced transcript abundance in the hippocampus of stress-related mineralocorticoid receptor and glucocorticoid receptor genes, as well as nuclear factor kappa beta gene expression, implicated in inflammatory processes. Together, these data indicate that chronic high fat diet consumption may increase anxiety-like behaviour at least in part via alterations in glucocorticoid signalling mechanisms in limbic brain regions.
Lalanza, Jaume F.; Caimari, Antoni; del Bas, Josep M.; Torregrosa, Daniel; Cigarroa, Igor; Pallàs, Mercè; Capdevila, Lluís; Arola, Lluís; Escorihuela, Rosa M.
Among adolescents, overweight, obesity and metabolic syndrome are rapidly increasing in recent years as a consequence of unhealthy palatable diets. Animal models of diet-induced obesity have been developed, but little is known about the behavioural patterns produced by the consumption of such diets. The aim of the present study was to determine the behavioural and biochemical effects of a cafeteria diet fed to juvenile male and female rats, as well as to evaluate the possible recovery from these effects by administering standard feeding during the last week of the study. Two groups of male and female rats were fed with either a standard chow diet (ST) or a cafeteria (CAF) diet from weaning and for 8 weeks. A third group of males (CAF withdrawal) was fed with the CAF diet for 7 weeks and the ST in the 8th week. Both males and females developed metabolic syndrome as a consequence of the CAF feeding, showing overweight, higher adiposity and liver weight, increased plasma levels of glucose, insulin and triglycerides, as well as insulin resistance, in comparison with their respective controls. The CAF diet reduced motor activity in all behavioural tests, enhanced exploration, reduced anxiety-like behaviour and increased social interaction; this last effect was more pronounced in females than in males. When compared to animals only fed with a CAF diet, CAF withdrawal increased anxiety in the open field, slightly decreased body weight, and completely recovered the liver weight, insulin sensitivity and the standard levels of glucose, insulin and triglycerides in plasma. In conclusion, a CAF diet fed to young animals for 8 weeks induced obesity and metabolic syndrome, and produced robust behavioural changes in young adult rats, whereas CAF withdrawal in the last week modestly increased anxiety, reversed the metabolic alterations and partially reduced overweight. PMID:24482678
Lalanza, Jaume F; Caimari, Antoni; del Bas, Josep M; Torregrosa, Daniel; Cigarroa, Igor; Pallàs, Mercè; Capdevila, Lluís; Arola, Lluís; Escorihuela, Rosa M
Among adolescents, overweight, obesity and metabolic syndrome are rapidly increasing in recent years as a consequence of unhealthy palatable diets. Animal models of diet-induced obesity have been developed, but little is known about the behavioural patterns produced by the consumption of such diets. The aim of the present study was to determine the behavioural and biochemical effects of a cafeteria diet fed to juvenile male and female rats, as well as to evaluate the possible recovery from these effects by administering standard feeding during the last week of the study. Two groups of male and female rats were fed with either a standard chow diet (ST) or a cafeteria (CAF) diet from weaning and for 8 weeks. A third group of males (CAF withdrawal) was fed with the CAF diet for 7 weeks and the ST in the 8th week. Both males and females developed metabolic syndrome as a consequence of the CAF feeding, showing overweight, higher adiposity and liver weight, increased plasma levels of glucose, insulin and triglycerides, as well as insulin resistance, in comparison with their respective controls. The CAF diet reduced motor activity in all behavioural tests, enhanced exploration, reduced anxiety-like behaviour and increased social interaction; this last effect was more pronounced in females than in males. When compared to animals only fed with a CAF diet, CAF withdrawal increased anxiety in the open field, slightly decreased body weight, and completely recovered the liver weight, insulin sensitivity and the standard levels of glucose, insulin and triglycerides in plasma. In conclusion, a CAF diet fed to young animals for 8 weeks induced obesity and metabolic syndrome, and produced robust behavioural changes in young adult rats, whereas CAF withdrawal in the last week modestly increased anxiety, reversed the metabolic alterations and partially reduced overweight.
Sakharkar, Amul J; Zhang, Huaibo; Tang, Lei; Baxstrom, Kathryn; Shi, Guangbin; Moonat, Sachin; Pandey, Subhash C
Recent studies have demonstrated the involvement of epigenetic mechanisms in psychiatric disorders, including alcoholism. Here, we investigated the effects of histone deacetylase (HDAC) inhibitor, trichostatin A (TSA) on amygdaloid HDAC-induced histone deacetylation and neuropeptide Y (NPY) expression and on anxiety-like and alcohol-drinking behaviours in alcohol-preferring (P) and -non-preferring (NP) rats. It was found that P rats displayed higher anxiety-like and alcohol-drinking behaviours, higher amygdaloid nuclear, but not cytosolic, HDAC activity, which was associated with increased HDAC2 protein levels and deficits in histone acetylation and NPY expression in the central (CeA) and medial nucleus of amygdala (MeA), as compared to NP rats. TSA treatment attenuated the anxiety-like and alcohol-drinking behaviours, with concomitant reductions in amygdaloid nuclear, but not cytosolic HDAC activity, and HDAC2, but not HDAC4, protein levels in the CeA and MeA of P rats, without effect in NP rats. TSA treatment also increased global histone acetylation (H3-K9 and H4-K8) and NPY expression in the CeA and MeA of P, but not in NP rats. Histone H3 acetylation within the NPY promoter was also innately lower in the amygdala of P rats compared with NP rats; which was normalized by TSA treatment. Voluntary ethanol intake in P, but not NP rats, produced anxiolytic effects and decreased the HDAC2 levels and increased histone acetylation in the CeA and MeA. These results suggest that higher HDAC2 expression-related deficits in histone acetylation may be involved in lower NPY expression in the amygdala of P rats, and operative in controlling anxiety-like and alcohol-drinking behaviours.
Gur, Tamar L; Shay, Lena; Palkar, Aditi Vadodkar; Fisher, Sydney; Varaljay, Vanessa A; Dowd, Scot; Bailey, Michael T
Recent studies demonstrate that exposure to stress changes the composition of the intestinal microbiota, which is associated with development of stress-induced changes to social behavior, anxiety, and depression. Stress during pregnancy has also been related to the emergence of these disorders; whether commensal microbes are part of a maternal intrauterine environment during prenatal stress is not known. Here, we demonstrate that microbiome changes are manifested in the mother, and also found in female offspring in adulthood, with a correlation between stressed mothers and female offspring. Alterations in the microbiome have been shown to alter immune responses, thus we examined cytokines in utero. IL-1β was increased in placenta and fetal brain from offspring exposed to the prenatal stressor. Because IL-1β has been shown to prevent induction of brain derived neurotrophic factor (BDNF), we examined BDNF and found a reduction in female placenta and adult amygdala, suggesting in utero impact on neurodevelopment extending into adulthood. Furthermore, gastrointestinal microbial communities were different in adult females born from stressed vs. non-stressed pregnancies. Adult female offspring also demonstrated increased anxiety-like behavior and alterations in cognition, suggesting a critical window where stress is able to influence the microbiome and the intrauterine environment in a deleterious manner with lasting behavioral consequences. The microbiome may be a key link between the intrauterine environment and adult behavioral changes.
Machawal, Lalit; Kumar, Anil
Dietary supplements are widely used to manage stress and related consequences. However, the exact pathological mechanism and cellular cascades involved in the action of these supplements are not properly understood so far. Therefore, the present study has been designed to explore the neuroprotective mechanism of rutin against immobilization stress-induced anxiety-like behavioural and oxidative damage in mice. Laboratory Animal Centre A-strain (laca) mice were used in the present study. Rutin (20, 40, and 80 mg/kg), l-arginine (100 mg/kg), l-nitroarginine methyl ester (l-NAME) (5 mg/kg) and vitamin-E (50 mg/kg) were administered for 5 days before 6h immobilization stress on 6th day. Various behavioural parameters (mirror chamber test, locomotor activity) followed by biochemical parameters (lipid peroxidation, nitrite concentration, reduced glutathione and catalase) in brain and then serum corticosterone level were assessed. 6 h immobilization stress produced anxiety-like behavioural in mirror chamber test, raised corticosterone level and oxidative stress (as evidenced by rise in lipid peroxidation, nitrite concentration, depletion of reduced glutathione and catalase activity) significantly as compared to naive group. 5 days pre-treatment with rutin (40 and 80 mg/kg) causes a significant attenuation of locomotor activity, corticosterone level, oxidative stress as compared to control. Further, l-arginine (100 mg/kg) pre-treatment significantly reversed the protective effect of rutin (40 mg/kg) in 6 h immobilized animals. However, l-NAME (5 mg/kg) pre-treatment with rutin (40 mg/kg) potentiated their protective effect which was significant as compared to their effect per se. The present study suggests the involvement of nitric oxide mechanism in the neuroprotective effect of rutin against immobilization stress-induced anxiety-like behaviour and oxidative damage in mice.
Baldini, Sara; Restani, Laura; Baroncelli, Laura; Coltelli, Maila; Franco, Roberta; Cenni, Maria Cristina; Maffei, Lamberto; Berardi, Nicoletta
Early life experiences can affect brain development, contributing to shape interindividual differences in stress vulnerability and anxiety-like behavior. In rodents, high levels of maternal care have long-lasting positive effects on the behavior of the offspring and stress response; post-weaning rearing in an enriched environment (EE) or massage counteract the negative effects of maternal separation or prenatal stressors. We recently found that insulin-like growth factor 1 (IGF-1) is a key mediator of early EE or massage on brain development. Whether early enrichment of experience can induce long-lasting effects on anxiety-like behavior and whether IGF-1 is involved in these effects is not known. We assessed anxiety-like behavior by means of the elevated plus maze in control adult rats and in adult rats subjected to early EE or to massage. We found that both EE and massage reduced adult anxiety-like behavior. Early IGF-1 systemic injections in rat pups reared in standard condition mimic the effects of EE and massage, reducing anxiety-like behavior in the adult; blocking early IGF-1 action in massaged and EE animals prevents massage and EE effects. In EE and IGF-1-treated animals, we assessed the hippocampal expression of glucocorticoid receptors (GRs) at postnatal day 12 (P12) and P60, finding a significantly higher GR expression at P60 for both treatments. These results suggest that IGF-1 could be involved in mediating the long-lasting effects of early life experiences on vulnerability/resilience to stress in adults.
Kumar, Manoj; Singh, Surya P.
The present study was aimed to investigate behavioural and biochemical effects of chronic exposure of amplitude modulated and non-modulated microwave radiation on laboratory mice. Chronic microwave exposures were executed with 2.45 GHz of either modulated (power density, 0.029 mW/cm2; specific absorption rate, 0.019 W/Kg with sinusoidal modulation of 400 Hz) or nonmodulated continuous sinusoidal wave (power density, 0.033 mW/cm2; specific absorption rate, 0.023 W/Kg) for 2 hrs daily for 1 month. Mice subjected to non-modulated microwave exposure had significantly increased acetylcholinesterase activity and increased intracellular calcium and nitric oxide levels in the cerebral cortex and hippocampus, and also had increased glucose and corticosterone levels in blood compared to control mice. These non-modulated microwave-exposed mice exhibited anxiety-like and depression-like behaviours. In contrast, mice exposed to modulated microwave for the same period did not show such changes in concomitant biochemical and behavioural analyses. These results suggest that chronic non-modulated microwave, but not modulated microwave, radiation may cause anxiety-like and depression-like behaviours and calcium- and NO-related biochemical changes in the brain. PMID:28035182
Wallace, Victoria C.J.; Segerdahl, Andrew R.; Blackbeard, Julie; Pheby, Timothy; Rice, Andrew S.C.
Neuropathic pain is commonly associated with affective disorders such as anxiety and depression. We have previously characterised a rodent model of HIV, anti-retroviral-associated neuropathy in which rats develop hypersensitivity to a punctate mechanical stimulus and display anxiety-like behaviour in the open field paradigm. To assess the potential of this behavioural paradigm for the assessment of pain related co-morbidities in rodent models of pain, here we test the sensitivity of this anxiety-like behaviour to the analgesic agents gabapentin and morphine in comparison to the known anxiolytic drug diazepam. We found that gabapentin (30 mg/kg, i.p.) and morphine (2.5 mg/kg, i.p.), which reduce mechanical hypersensitivity in these rats, significantly reduces measures of thigmotaxis in the open field. The effect of gabapentin and morphine did not differ significantly from diazepam (1 mg/kg, i.p.). This study highlights the potential use of this rodent model and behavioural paradigm in the validation of the affective component of novel analgesic pharmacological targets and elucidation of underlying pathophysiological mechanisms. PMID:18926876
Wallace, Victoria C J; Segerdahl, Andrew R; Blackbeard, Julie; Pheby, Timothy; Rice, Andrew S C
Neuropathic pain is commonly associated with affective disorders such as anxiety and depression. We have previously characterised a rodent model of HIV, anti-retroviral-associated neuropathy in which rats develop hypersensitivity to a punctate mechanical stimulus and display anxiety-like behaviour in the open field paradigm. To assess the potential of this behavioural paradigm for the assessment of pain related co-morbidities in rodent models of pain, here we test the sensitivity of this anxiety-like behaviour to the analgesic agents gabapentin and morphine in comparison to the known anxiolytic drug diazepam. We found that gabapentin (30 mg/kg, i.p.) and morphine (2.5 mg/kg, i.p.), which reduce mechanical hypersensitivity in these rats, significantly reduces measures of thigmotaxis in the open field. The effect of gabapentin and morphine did not differ significantly from diazepam (1 mg/kg, i.p.). This study highlights the potential use of this rodent model and behavioural paradigm in the validation of the affective component of novel analgesic pharmacological targets and elucidation of underlying pathophysiological mechanisms.
Kudwa, Andrea E; McGivern, Robert F; Handa, Robert J
The hypothalamic-pituitary-adrenal (HPA) axis is activated in response to stressors and is controlled by neurons residing in the paraventricular nucleus of the hypothalamus (PVN). Although gonadal steroid hormones can influence HPA reactivity to stressors, the exact mechanism of action is not fully understood. It is known, however, that estrogen receptor β (ERβ) inhibits HPA reactivity and decreases anxiety-like behavior in rodents. Since ERβ is co-expressed with oxytocin (OT) in neurons of the PVN, an ERβ-selective agonist was utilized to test the whether ERβ decreases stress-induced HPA reactivity and anxiety-like behaviors via an OTergic pathway. Adult gonadectomized male and female rats were administered diarylpropionitrile, or vehicle, peripherally for 5days. When tested for anxiety-like behavior on the elevated plus maze (EPM), diarylpropionitrile-treated males and females significantly increased time on the open arm of the EPM compared to vehicle controls indicating that ERβ reduces anxiety-like behaviors. One week after behavioral evaluation, rats were subjected to a 20minute restraint stress. Treatment with diarylpropionitrile reduced CORT and ACTH responses in both males and females. Subsequently, another group of animals was implanted with cannulae directed at the lateral ventricle. One week later, rats underwent the same protocol as above but with the additional treatment of intracerebroventricular infusion with an OT antagonist (des Gly-NH2 d(CH2)5 [Tyr(Me)(2), Thr(4)] OVT) or VEH, 20min prior to behavioral evaluation. OT antagonist treatment blocked the effects of diarylpropionitrile on the display of anxiety-like behaviors and plasma CORT levels. These data indicate that ERβ and OT interact to modulate the HPA reactivity and the display of anxiety-like behaviors.
Yang, Liu; Yue, Na; Zhu, Xiaocang; Han, Qiuqin; Li, Bin; Liu, Qiong; Wu, Gencheng; Yu, Jin
The present study was designed to investigate the effects of electroacupuncture (EA) on depressive-like and anxiety-like behaviours and neural progenitors in the hippocampal dentate gyrus (DG) in a chronic unpredictable stress (CUS) rat model of depression. After being exposed to a CUS procedure for 2 weeks, rats were subjected to EA treatment, which was performed on acupoints Du-20 (Bai-Hui) and GB-34 (Yang-Ling-Quan), once every other day for 15 consecutive days (including 8 treatments), with each treatment lasting for 30 min. The behavioural tests (i.e., forced swimming test, elevated plus-maze test, and open-field entries test) revealed that EA alleviated the depressive-like and anxiety-like behaviours of the stressed rats. Immunohistochemical results showed that proliferative cells (BrdU-positive) in the EA group were significantly larger in number compared with the Model group. Further, the results showed that EA significantly promoted the proliferation of amplifying neural progenitors (ANPs) and simultaneously inhibited the apoptosis of quiescent neural progenitors (QNPs). In a word, the mechanism underlying the antidepressant-like effects of EA is associated with enhancement of ANPs proliferation and preserving QNPs from apoptosis. PMID:24719647
Shehu, Abubakar; Mohammed, Aliyu; Magaji, Rabiu Abdussalam; Muhammad, Mustapha Shehu
Research on the effects of Mobile phone radio frequency emissions on biological systems has been focused on noise and vibrations as auditory stressors. This study investigated the potential effects of exposure to mobile phone electromagnetic field radiation, ringtone and vibration on anxiety-like behaviour and oxidative stress biomarkers in albino wistar rats. Twenty five male wistar rats were randomly divided into five groups of 5 animals each: group I: exposed to mobile phone in switched off mode (control), group II: exposed to mobile phone in silent mode, group III: exposed to mobile phone in vibration mode, group IV: exposed to mobile phone in ringtone mode, group V: exposed to mobile phone in vibration and ringtone mode. The animals in group II to V were exposed to 10 min call (30 missed calls for 20 s each) per day for 4 weeks. Neurobehavioural studies for assessing anxiety were carried out 24 h after the last exposure and the animals were sacrificed. Brain samples were collected for biochemical evaluation immediately. Results obtained showed a significant decrease (P < 0.05) in open arm duration in all the experimental groups when compared to the control. A significant decrease (P < 0.05) was also observed in catalase activity in group IV and V when compared to the control. In conclusion, the results of the present study indicates that 4 weeks exposure to electromagnetic radiation, vibration, ringtone or both produced a significant effect on anxiety-like behavior and oxidative stress in young wistar rats.
Impaired fear extinction retention and increased anxiety-like behaviours induced by limited daily access to a high-fat/high-sugar diet in male rats: Implications for diet-induced prefrontal cortex dysregulation.
Baker, Kathryn D; Reichelt, Amy C
Anxiety disorders and obesity are both common in youth and young adults. Despite increasing evidence that over-consumption of palatable high-fat/high-sugar "junk" foods leads to adverse neurocognitive outcomes, little is known about the effects of palatable diets on emotional memories and fear regulation. In the present experiments we examined the effects of daily 2h consumption of a high-fat/high-sugar (HFHS) food across adolescence on fear inhibition and anxiety-like behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired retention of fear extinction and increased anxiety-like behaviour in an emergence test compared to rats fed a standard diet. The HFHS-fed rats displayed diet-induced changes in prefrontal cortex (PFC) function which were detected by altered expression of GABAergic parvalbumin-expressing inhibitory interneurons and the stable transcription factor ΔFosB which accumulates in the PFC in response to chronic stimuli. Immunohistochemical analyses of the medial PFC revealed that animals fed the HFHS diet had fewer parvalbumin-expressing cells and increased levels of FosB/ΔFosB expression in the infralimbic cortex, a region implicated in the consolidation of fear extinction. There was a trend towards increased IBA-1 immunoreactivity, a marker of microglial activation, in the infralimbic cortex after HFHS diet exposure but expression of the extracellular glycoprotein reelin was unaffected. These findings demonstrate that a HFHS diet during adolescence is associated with reductions of prefrontal parvalbumin neurons and impaired fear inhibition in adulthood. Adverse effects of HFHS diets on the mechanisms of fear regulation may precipitate a vulnerability in obese individuals to the development of anxiety disorders.
Le Roy, Chloé; Laboureyras, Emilie; Laulin, Jean-Paul; Simonnet, Guy
In humans, hyperalgesia, tolerance and anxiety disorders are common symptoms during heroin withdrawal syndrome. Significant evidence supports a role of NMDA receptors in these phenomena. Because polyamines may positively modulate the functioning of NMDA receptors and mainly originate from dietary intake, one hypothesis is that a polyamine deficient diet (PD diet) may reduce withdrawal symptoms. To address this question, we investigated the ability of a PD diet to prevent or to alleviate some symptoms of withdrawal syndrome as hyperalgesia, and increased anxiety-like behaviour in rats receiving 14 once daily subcutaneous heroin injections. Here, we show that a PD diet has both preventive and curative properties for reducing certain signs of withdrawal such as hyperalgesia, tolerance and increased anxiety-like behaviour observed in rats fed with a standard diet. Moreover, in heroin-withdrawn rats which were returned to basal pain sensitivity level, hyperalgesia following acute analgesia induced by a single heroin dose was observed in heroin-treated rats fed with standard diet, not in rats fed with a PD diet. Similarly, a stress-induced hyperalgesia induced by a non-nociceptive environmental stress session was observed in heroin-treated rats fed with standard diet. In contrast, a stress-induced analgesia was observed in heroin-treated rats fed with a PD diet, as it was observed in non heroin-treated rats. Since a PD diet for several weeks did not induce appreciable side-effects in rats, these preclinical results suggest that a PD diet could be an effective strategy for improving the relief of certain negative emotional states of heroin withdrawal syndrome and to allow reducing other medications generally used, such as opioid maintenance drugs.
Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M
Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations.
Ishikawa, Junko; Nishimura, Ryoichi; Ishikawa, Akinori
Early-life stress increases the prevalence of psychiatric diseases associated with emotional dysregulation. Emotional regulation requires the inhibitory influence of the medial prefrontal cortex (mPFC) on amygdalar activity, and dysfunction of this system is believed to induce anxiety. Because mPFC and amygdala have dense reciprocal connections and projections between them continue to develop until adolescence, early-life stress may impair the function of this circuit and cause emotional dysregulation. We examined the effects of stress during circuit development on anxiety-like behaviors, neural activities in the mPFC and amygdala, and impulse transmission in the mPFC-amygdala circuit in adult rats. Early-life stress, unpredictable stress twice a day for 12 days following early weaning, increased anxiety-like behaviors in the open-field and elevated plus-maze tests. In the open-field test, stress altered Fos expression in the mPFC and amygdala. Compared to non-stressed rats, which were exposed to neither unpredictable stress nor early weaning, stressed rats exhibited decreased Fos expression in the right superficial layers of the infralimbic cortex and increased Fos expression in the right basolateral amygdala and both sides of the central amygdala. Electrophysiological analysis revealed that excitatory latencies of mPFC neurons to amygdalar stimulation in stressed rats were significantly longer than control rats in the right, but not left, hemisphere. Stress had no effect on excitatory latencies of amygdalar neurons to mPFC stimulation in the mPFC-amygdala circuits in the both hemisphere. These data suggest that early-life stress impairs the mPFC-amygdala circuit development, resulting in imbalanced mPFC and amygdala activities and anxiety-like behaviors.
Meng, Fan-Tao; Zhao, Jun; Fang, Hui; Liu, Ya-Jing
The apolipoprotein E (ApoE) ɛ4 allele (ApoE4) is an important genetic risk factor for the pathogenesis of Alzheimer's disease (AD). In addition to genetic factors, environmental factors such as stress may play a critical role in AD pathogenesis. This study was designed to investigate the anxiety-like behavioral and cognitive changes in different human glial fibrillary acidic protein (GFAP)-ApoE transgenic adult male mice under chronic stress conditions. On the open field test, anxiety-like behavior was increased in the non-stressed GFAP-ApoE4 transgenic mice relative to the corresponding GFAP-ApoE3 (ApoE ɛ3 allele) mice. Anxiety-like behavior was increased in the stressed GFAP-ApoE3 mice relative to non-stressed GFAP-ApoE3 mice, but was unexpectedly decreased in the stressed GFAP-ApoE4 mice relative to non-stressed GFAP-ApoE4 mice. On the novel object recognition task, both GFAP-ApoE4 and GFAP-ApoE3 mice exhibited long-term non-spatial memory impairment after chronic stress. Interestingly, short-term non-spatial memory impairment (based on the novel object recognition task) was observed only in the stressed GFAP-ApoE4 male mice relative to non-stressed GFAP-ApoE4 transgenic mice. In addition, short-term spatial memory impairment was observed in the stressed GFAP-ApoE3 transgenic male mice relative to non-stressed GFAP-ApoE3 transgenic male mice; however, short-term spatial memory performance of GFAP-ApoE4 transgenic male mice was not reduced compared to non-stressed control mice based on the Y-maze task. In conclusion, our findings suggested that chronic stress affects anxiety-like behavior and spatial and non-spatial memory in GFAP-ApoE transgenic mice in an ApoE isoform-dependent manner.
Burgado, Jillybeth; Harrell, Constance S; Eacret, Darrell; Reddy, Renuka; Barnum, Christopher J; Tansey, Malú G; Miller, Andrew H; Wang, Huichen; Neigh, Gretchen N
Psychological stress can have devastating and lasting effects on a variety of behaviors, especially those associated with mental illnesses such as anxiety and depression. Animal models of chronic stress are frequently used to elucidate the mechanisms underlying the relationship between stress and mental health disorders and to develop improved treatment options. The current study expands upon a novel chronic stress paradigm for mice: predatory stress. The predatory stress model incorporates the natural predator-prey relationship that exists among rats and mice and allows for greater interaction between the animals, in turn increasing the extent of the stressful experience. In this study, we evaluated the behavioral effects of exposure to 15 days of predatory stress on an array of behavioral indices. Up to 2 weeks after the end of stress, adult male mice showed an increase of anxiety-like behaviors as measured by the open field and social interaction tests. Animals also expressed an increase in depressive-like behavior in the sucrose preference test. Notably, performance on the novel object recognition task, a memory test, improved after predatory stress. Taken as a whole, our results indicate that 15 exposures to this innovative predatory stress paradigm are sufficient to elicit robust anxiety-like behaviors with evidence of co-morbid depressive-like behavior, as well as changes in cognitive behavior in male mice.
Fraga, Mabel C; Moura, Egberto G; Silva, Juliana Oliveira; Bonomo, Isabela Teixeira; Filgueiras, Cláudio C; Abreu-Villaça, Yael; Passos, Magna C F; Lisboa, Patrícia C; Manhães, Alex C
Maternal hypoprolactinemia at the end of lactation in rats reduces milk production and is associated with offspring's malnutrition. Since malnutrition during development is also known to have long lasting effects on cognition and emotion, in the present study we tested the hypothesis that maternal hypoprolactinemia, induced by bromocriptine treatment, at the end of the lactating period affects memory/learning, novelty-seeking and anxiety-like behaviors in adult male Wistar rats using, respectively, the radial arm water maze (RAWM), the hole board (HB) arena and the elevated plus-maze (EPM). We also analyzed serum corticosterone and thyroid hormone levels at postnatal day (PN) 21. Lactating dams were treated with bromocriptine (BRO, 1mg twice a day, inhibiting prolactin) or saline from PN19 to 21 (the last 3 days of lactation). BRO offspring had hypercorticosteronemia and hypothyroidism at PN21. In the RAWM, reductions in latency observed in CON rats were initially more accentuated than in BRO ones. By the end of the testing period, latencies became similar between groups. No difference was observed between groups regarding the number of nose-pokes in the HB. In the EPM, BRO rats stayed less time in and had fewer entries into the open-arms than CON ones. This pattern of results indicates that maternal bromocriptine treatment at the end of the lactating period results in poorer memory/learning performance and in higher levels of anxiety-like behavior in the adult offspring, demonstrating that even a relatively short period of malnutrition during development can have long lasting detrimental effects regarding cognition and emotion.
Zhu, W; Mao, Z; Zhu, C; Li, M; Cao, C; Guan, Y; Yuan, J; Xie, G; Guan, X
Repeated exposure to cocaine during adolescence may affect both physical and psychological conditions in the brain, and increase the risk of psychiatric disorders and addiction behaviors in adulthood. Adolescence represents a critical development period for the hippocampus. Moreover, different regions of the hippocampus are involved in different functions. Dorsal hippocampus (dHP) has been implicated in learning and memory, whereas ventral hippocampus (vHP) plays an important role in emotional processing. In this study, the rats that were exposed to cocaine during adolescence (postnatal days, P28-P42) showed higher anxiety-like behavior in the elevated plus maze test in adulthood (P80), but displayed normal spatial learning and memory in the Morris water maze test. Furthermore, repeated exposure to cocaine during adolescence lead to alterations in morphology of pyramidal neurons, activities of astrocytes, and levels of proteins that involved in synaptic transmission, apoptosis, inflammation and addiction in both dHP and vHP of adult rats. These findings suggest that repeated exposure to cocaine during adolescence in rats may elicit morphologic and neurochemical changes in the hippocampus when the animals reach adulthood. These changes may contribute to the increased susceptibility for psychiatric disorders and addiction seen in adults.
Guha, Suman K; Tillu, Rucha; Sood, Ankit; Patgaonkar, Mandar; Nanavaty, Ishira N; Sengupta, Arjun; Sharma, Shobhona; Vaidya, Vidita A; Pathak, Sulabha
Cerebral malaria is associated with cerebrovascular damage and neurological sequelae. However, the neurological consequences of uncomplicated malaria, the most prevalent form of the disease, remain uninvestigated. Here, using a mild malaria model, we show that a single Plasmodium chabaudi adami infection in adult mice induces neuroinflammation, neurogenic, and behavioral changes in the absence of a blood-brain barrier breach. Using cytokine arrays we show that the infection induces differential serum and brain cytokine profiles, both at peak parasitemia and 15days post-parasite clearance. At the peak of infection, along with the serum, the brain also exhibited a definitive pro-inflammatory cytokine profile, and gene expression analysis revealed that pro-inflammatory cytokines were also produced locally in the hippocampus, an adult neurogenic niche. Hippocampal microglia numbers were enhanced, and we noted a shift to an activated profile at this time point, accompanied by a striking redistribution of the microglia to the subgranular zone adjacent to hippocampal neuronal progenitors. In the hippocampus, a distinct decline in progenitor turnover and survival was observed at peak parasitemia, accompanied by a shift from neuronal to glial fate specification. Studies in transgenic Nestin-GFP reporter mice demonstrated a decline in the Nestin-GFP(+)/GFAP(+) quiescent neural stem cell pool at peak parasitemia. Although these cellular changes reverted to normal 15days post-parasite clearance, specific brain cytokines continued to exhibit dysregulation. Behavioral analysis revealed selective deficits in social and anxiety-like behaviors, with no change observed in locomotor, cognitive, and depression-like behaviors, with a return to baseline at recovery. Collectively, these findings indicate that even a single episode of mild malaria results in alterations of the brain cytokine profile, causes specific behavioral dysfunction, is accompanied by hippocampal microglial
Dworkin, Sebastian; Auden, Alana; Partridge, Darren D; Daglas, Maria; Medcalf, Robert L; Mantamadiotis, Theo; Georgy, Smitha R; Darido, Charbel; Jane, Stephen M; Ting, Stephen B
The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here we show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviours. Using both Grhl3-knockout mice (Grhl3(-/-) ), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3(flox/flox) ), we performed histological expression analyses and behavioural tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety and stress. We found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain, however aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviours suggestive of decreased fear and anxiety. We conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behaviour or hyperactivity. This article is protected by copyright. All rights reserved.
Fedotova, Julia; Pivina, Svetlana; Sushko, Anastasia
The present preclinical study was created to determine the therapeutic effects of vitamin D hormone treatment as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol (17β-E2) on anxiety-like behavior in female rats with long-term absence of estrogen. Accordingly, the aim of the current study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg subcutaneously, SC, once daily, for 14 days) on the anxiety-like state after long-term ovariectomy in female rats. Twelve weeks postovariectomy, cholecalciferol was administered to ovariectomized (OVX) rats and OVX rats treated with 17β-E2 (0.5 µg/rat SC, once daily, for 14 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light/dark test (LDT), and locomotor and grooming activities were tested in the open field test (OFT). Cholecalciferol at two doses of 1.0 and 2.5 mg/kg alone or in combination with 17β-E2 produced anxiolytic-like effects in OVX rats as evidenced in the EPM and the LDT, as well as increased grooming activity in the OFT. Our results indicate that cholecalciferol, at two doses of 1.0 and 2.5 mg/kg, has a profound anxiolytic-like effects in the experimental rat model of long-term estrogen deficiency. PMID:28054941
Zhang, Xiaosong; Wang, Qi; Wang, Yan; Hu, Jingmin; Jiang, Han; Cheng, Wenwen; Ma, Yuchao; Liu, Mengxi; Sun, Anji; Zhang, Xinxin; Li, Xiaobai
Stress during pregnancy may cause neurodevelopmental and psychiatric disorders. However, the mechanisms are largely unknown. Currently, pro-inflammatory cytokines have been identified as a risk factor for depression and anxiety disorder. Unfortunately, there is very little research on the long-term effects of prenatal stress on the neuroinflammatory system of offspring. Moreover, the relationship between antidepressant treatment and cytokines in the central nervous system, especially in the hippocampus, an important emotion modulation center, is unclear. Therefore, the aim of this study was to determine the effects of prenatal chronic mild stress during development on affective-like behaviors and hippocampal cytokines in adult offspring, and to verify whether antidepressant (duloxetine) administration from early adulthood could prevent the harmful consequences. To do so, prenatally stressed and non-stressed Sprague-Dawley rats were treated with either duloxetine (10mg/kg/day) or vehicle from postnatal day 60 for 21days. Adult offspring were divided into four groups: 1) prenatal stress+duloxetine treatment, 2) prenatal stress+vehicle, 3) duloxetine treatment alone, and 4) vehicle alone. Adult offspring were assessed for anxiety-like behavior using the open field test and depression-like behavior using the forced swim test. Brains were analyzed for pro-inflammatory cytokine markers in the hippocampus via real-time PCR. Results demonstrate that prenatal stress-induced anxiety- and depression-like behaviors are associated with an increase in hippocampal inflammatory mediators, and duloxetine administration prevents the increased hippocampal pro-inflammatory cytokine interleukin-6 and anxiety- and depression-like behavior in prenatally stressed adult offspring. This research provides important evidence on the long-term effect of PNS exposure during development in a model of maternal adversity to study the pathogenesis of depression and its therapeutic interventions.
Hu, Min; Richard, Jennifer Elise; Maliqueo, Manuel; Kokosar, Milana; Fornes, Romina; Benrick, Anna; Jansson, Thomas; Ohlsson, Claes; Wu, Xiaoke; Skibicka, Karolina Patrycja; Stener-Victorin, Elisabet
During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers.
Hu, Min; Richard, Jennifer Elise; Maliqueo, Manuel; Kokosar, Milana; Fornes, Romina; Benrick, Anna; Jansson, Thomas; Ohlsson, Claes; Wu, Xiaoke; Skibicka, Karolina Patrycja; Stener-Victorin, Elisabet
During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers. PMID:26578781
Maximino, Caio; da Silva, Annanda Waneza Batista; Araújo, Juliana; Lima, Monica Gomes; Miranda, Vanessa; Puty, Bruna; Benzecry, Rancés; Picanço-Diniz, Domingos Luiz Wanderley; Gouveia, Amauri; Oliveira, Karen Renata Matos; Herculano, Anderson Manoel
A major hindrance for the development of psychiatric drugs is the prediction of how treatments can alter complex behaviors in assays which have good throughput and physiological complexity. Here we report the development of a medium-throughput screen for drugs which alter anxiety-like behavior in adult zebrafish. The observed phenotypes were clustered according to shared behavioral effects. This barcoding procedure revealed conserved functions of anxiolytic, anxiogenic and psychomotor stimulating drugs and predicted effects of poorly characterized compounds on anxiety. Moreover, anxiolytic drugs all decreased, while anxiogenic drugs increased, serotonin turnover. These results underscore the power of behavioral profiling in adult zebrafish as an approach which combines throughput and physiological complexity in the pharmacological dissection of complex behaviors.
Maximino, Caio; da Silva, Annanda Waneza Batista; Araújo, Juliana; Lima, Monica Gomes; Miranda, Vanessa; Puty, Bruna; Benzecry, Rancés; Picanço-Diniz, Domingos Luiz Wanderley; Gouveia, Amauri; Oliveira, Karen Renata Matos; Herculano, Anderson Manoel
A major hindrance for the development of psychiatric drugs is the prediction of how treatments can alter complex behaviors in assays which have good throughput and physiological complexity. Here we report the development of a medium-throughput screen for drugs which alter anxiety-like behavior in adult zebrafish. The observed phenotypes were clustered according to shared behavioral effects. This barcoding procedure revealed conserved functions of anxiolytic, anxiogenic and psychomotor stimulating drugs and predicted effects of poorly characterized compounds on anxiety. Moreover, anxiolytic drugs all decreased, while anxiogenic drugs increased, serotonin turnover. These results underscore the power of behavioral profiling in adult zebrafish as an approach which combines throughput and physiological complexity in the pharmacological dissection of complex behaviors. PMID:25079766
Tenk, Christine M; Kavaliers, Martin; Ossenkopp, Klaus-Peter
Neonatal administration of the bacterial cell wall component, lipopolysaccharide (LPS) has been shown to alter a variety of behavioural and physiological processes in the adult rat, including altering adult anxiety-like behaviour. Research conducted to date, however, has produced conflicting findings with some results demonstrating increases in adult anxiety-like behaviour while others report decreases or no changes in anxiety-like behaviour. Thus, the current study conducted additional evaluation of the effects of neonatal LPS exposure on adult anxiety-like behaviours by comparing the behavioural outcomes in the more traditional light-dark test, together with the less common hyponeophagia to sucrose solution paradigm. Male and female Long-Evans rats were treated systemically with either LPS (50μg/kg) or saline (0.9%) on postnatal days 3 and 5. Animals were then tested in the light-dark apparatus on postnatal day 90 for 30min. Next, following 5 days of habituation to distilled water delivery in Lickometer drinking boxes, animal were tested for neophagia to a 10% sucrose solution (0.3M) for 30min daily on postnatal days 96 and 97. In the light-dark test, neonatal LPS treatment decreased adult anxiety-like behaviour in females, but not males. In contrast, neonatal exposure to LPS did not influence adult anxiety-like behaviour as measured by hyponeophagia, but altered the licking patterns of drinking displayed towards a novel, palatable sucrose solution in adult males and females, in a manner that may reflect a decrease in situational anxiety. The current study supports the idea that neonatal LPS treatment results in highly specific alterations of adult anxiety-like behaviour, the nature of which seems to depend not only on the measure of anxiety behaviour used, but also possibly, on the degree of anxiety experienced during the behavioural test.
Kinzig, Kimberly P.; Hargrave, Sara L.
Activity-based anorexia is a paradigm that induces increased physical activity, reduced food intake, and heightened activity of the hypothalamic-pituitary-adrenal axis in adult rats. To investigate whether experience with activity-based anorexia produced enduring effects on brain and behavior, female adolescent rats experienced activity-based anorexia during adolescence and were tested in adulthood for anxiety-like behavior on an elevated plus maze and in an open field. Analysis of elevated plus maze and open field behavior in adulthood revealed that rats that experienced activity-based anorexia during adolescence, but not rats that were simply food restricted, displayed increased anxiety-like behavior in adulthood. Plasma corticosterone and expression levels of corticotropin- releasing hormone mRNA in the hypothalamic paraventricular nucleus and in the central nucleus of the amygdala were significantly elevated in adult rats that had undergone activity-based anorexia in adolescence in response to the open field exposure, as compared to control rats. These data demonstrate enduring effects of adolescent activity-based anorexia on anxiety-like behavior and neuroendocrine factors critical in stress responsivity in adulthood. Furthermore, we demonstrate that activity-based anorexia during adolescence serves as a model whereby prolonged anxiety is induced, allowing for evaluation of the behavioral and neural correlates of mediating anxiety-like behaviors in adulthood. PMID:20566408
Bowers, Mallory E.; Ressler, Kerry J.
Epidemiological data suggest women are at increased risk for developing anxiety and depression, although the mechanisms for this sex/gender difference remain incompletely understood. Pre-clinical studies have begun to investigate sex-dependent emotional learning and behavior in rodents, particularly as it relates to psychopathology; however, information about how gonadal hormones interact with the central nervous system is limited. We observe greater anxiety-like behavior in male mice with global knockout of the cannabinoid 1 receptor (Cnr1) compared to male, wild-type controls as measured by percent open arm entries on an elevated plus maze test. A similar increase in anxiety-like behavior, however, is not observed when comparing female Cnr1 knockouts to female wild-type subjects. Although, ovariectomy in female mice did not reverse this effect, both male and female adult mice with normative development were sensitive to Cnr1 antagonist-mediated increases in anxiety-like behavior. Together, these data support an interaction between sex, potentially mediated by gonadal hormones, and the endocannabinoid system at an early stage of development that is critical for establishing adult anxiety-like behavior. PMID:26684509
Allen, David; Evans, Carys; Hider, Andrew; Hawkins, Sarah; Peckett, Helen; Morgan, Hugh
Considerable speculation is evident both within the scientific literature and popular media regarding possible links between Asperger syndrome and offending. A survey methodology that utilised quantitative data collection was employed to investigate the prevalence of offending behaviour amongst adults with Asperger Syndrome in a large geographical…
Walf, Alicia A.; Paris, Jason J.; Frye, Cheryl A.
.03). There were no statistically significant differences in the mirror maze and defensive burying task. Conclusion In this study of adult female rats, nociceptive behavior did not vary significantly with reproductive senescence, but anxiety-like behavior of rats did. PMID:19406372
Cumberland, Angela L; Palliser, Hannah K; Crombie, Gabrielle K; Walker, David W; Hirst, Jonathan J
Neurosteroids are essential for aiding proper fetal neurodevelopment. Pregnancy compromises such as preterm birth, prenatal stress and intrauterine growth restriction are associated with an increased risk of developing behavioural and mood disorders, particularly during adolescence. These pathologies involve the premature loss or alteration of trophic steroid hormones reaching the fetus leading to impaired neurodevelopment. While the specific programming mechanisms are yet to be fully elucidated, in adult life, dysfunctions of allopregnanolone action are prevalent in individuals with depression, post-traumatic stress disorder and anxiety disorders. The objective of this study was to assess if changes in concentrations of the neurosteroid, allopregnanolone, may be a fetal programming factor in priming the brain towards a negative behavioural phenotype during the childhood to adolescent period using a guinea pig model. Pregnant guinea pigs received either vehicle (45% (2-hydroxypropyl)-β-cyclodextrin) or the 5α-reductase inhibitor, finasteride (25mg/kg maternal weight) from gestational age 60 until spontaneous delivery (∼71days gestation). Male and female offspring from vehicle and finasteride treated dams were tested at postnatal day 20 (juvenile-equivalence) in an open field arena, and hippocampus and amygdala subsequently assessed for neurological changes in markers of development and GABA production pathways 24h later. Females with reduced allopregnanolone exposure in utero displayed increased neophobic-like responses to a change in their environment compared to female controls. There were no differences in the neurodevelopmental markers assessed; MAP2, NeuN, MBP, GFAP or GAD67 between intrauterine finasteride or vehicle exposure, in either the hippocampus or amygdala whereas GAT1 staining was decreased. This study indicates that an intrauterine reduction in the supply of allopregnanolone programs vulnerability of female offspring to anxiety-like disorders in
Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J
There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.
Richter, S Helene; Wollmann, Eva; Schmidt, Michaela; Zillmann, Uwe; Hellweg, Rainer; Sprengel, Rolf; Gass, Peter
Since the early 1930s, deep hypothermia (cryoanaesthesia) has been a useful anaesthetic in several types of surgery on neonatal rodents. Especially against the background of modern techniques in systems neuroscience, the method enjoys again increasing popularity. However, little is known about its effects on the subsequent adult behavioural and physiological profile. To systematically investigate the effects of neonatal cryoanaesthesia on adult basal and emotional behaviour as well as on physiological development, 59 C57BL/6 mouse pups were randomly assigned to one of three treatment groups: Pups of the first group were exposed to the hypothermia treatment (H) on postnatal day 3, while pups of the other two groups served as controls: These pups either remained in the home cage without any intervention (C), or were separated from the mother for 15 min (MS) to differentiate between effects of neonatal isolation alone versus hypothermia that inevitably goes along with neonatal isolation. Subsequent behavioural analyses were conducted during adulthood (P 84-P 130), including tests for exploratory, anxiety-like and depression-like behaviour. At the age of about 145 days mice were decapitated to record BDNF levels in the hippocampus and serum corticosterone. Altogether, H mice were found to display slightly increased anxiety levels on the O-Maze, but did not differ from the control animals in any other behavioural test. Subtle alterations in anxiety-like behaviour, however, were not accompanied by physiological changes in serum corticosterone and hippocampal BDNF levels, arguing against an overall long-lasting effect of neonatal hypothermia on the emotional profile of adult mice.
Pudell, Claudia; Vicente, Bianca A; Delattre, Ana M; Carabelli, Bruno; Mori, Marco A; Suchecki, Deborah; Machado, Ricardo B; Zanata, Sílvio M; Visentainer, Jesuí V; de Oliveira Santos Junior, Oscar; Lima, Marcelo M S; Ferraz, Anete C
Depression is increasingly present in the population, and its pathophysiology and treatment have been investigated with several animal models, including olfactory bulbectomy (Obx). Fish oil (FO) supplementation during the prenatal and postnatal periods decreases depression-like and anxiety-like behaviors. The present study evaluated the effect of FO supplementation on Obx-induced depressive-like behavior and cognitive impairment. Female rats received supplementation with FO during habituation, mating, gestation, and lactation, and their pups were subjected to Obx in adulthood; after the recovery period, the adult offspring were subjected to behavioral tests, and the hippocampal levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT) and the metabolite 5-hydroxyindoleacetic (5-HIAA) were determined. Obx led to increased anxiety-like and depressive-like behaviors, and impairment in the object location task. All behavioral changes were reversed by FO supplementation. Obx caused reductions in the levels of hippocampal BDNF and 5-HT, whereas FO supplementation restored these levels to normal values. In control rats, FO increased the hippocampal level of 5-HT and reduced that of 5-HIAA, indicating low 5-HT metabolism in this brain region. The present results indicate that FO supplementation during critical periods of brain development attenuated anxiety-like and depressive-like behaviors and cognitive dysfunction induced by Obx. These results may be explained by increased levels of hippocampal BDNF and 5-HT, two major regulators of neuronal survival and long-term plasticity in this brain structure.
Zhang, Zhuan; Hong, Juan; Zhang, Suyun; Zhang, Tingting; Sha, Sha; Yang, Rong; Qian, Yanning; Chen, Ling
Postpartum estrogen withdrawal is known to be a particularly vulnerable time for depressive symptoms. Ovariectomized adult mice (OVX-mice) treated with hormone-simulated pregnancy (HSP mice) followed by a subsequent estradiol benzoate (EB) withdrawal (EW mice) exhibited depression- and anxiety-like behaviors, as assessed by forced swim, tail suspension and elevated plus-maze, while HSP mice, OVX mice or EB-treated OVX mice (OVX/EB mice) did not. The survival and neurite growth of newborn neurons in hippocampal dentate gyrus were examined on day 5 after EW. Compared with controls, the numbers of 28-day-old BrdU(+) and BrdU(+)/NeuN(+) cells were increased in HSP mice but significantly decreased in EW mice; the numbers of 10-day-old BrdU(+) cells were increased in HSP mice and OVX/EB mice; and the density of DCX(+) fibers was reduced in EW mice and OVX mice. The phosphorylation of hippocampal NMDA receptor (NMDAr) NR2B subunit or Src was increased in HSP mice but decreased in EW mice. NMDAr agonist NMDA prevented the loss of 28-day-old BrdU(+) cells and the depression- and anxiety-like behaviors in EW mice. NR2B inhibitor Ro25-6981 or Src inhibitor dasatinib caused depression- and anxiety-like behaviors in HSP mice with the reduction of 28-day-old BrdU(+) cells. The hippocampal BDNF levels were reduced in EW mice and OVX mice. TrkB receptor inhibitor K252a reduced the density of DCX(+) fibers in HSP mice without the reduction of 28-day-old BrdU(+) cells, or the production of affective disorder. Collectively, these results indicate that postpartum estrogen withdrawal impairs hippocampal neurogenesis in mice that show depression- and anxiety-like behaviors.
Baruth, M.; Addy, C. L.; Wilcox, S.; Dowda, M.
Objectives: Individuals may engage in more than one risk behaviour at any given time. The extent to which risk behaviours cluster among African American adults has been largely unexplored. This study examined the prevalence and clustering of three risk behaviours among African American church members: smoking; low moderate-to-vigorous intensity…
Ji, Guangchen; Fu, Yu; Ruppert, Katherine A; Neugebauer, Volker
Corticotropin-releasing factor receptor CRF1 has been implicated in the neurobiological mechanisms of anxiety and depression. The amygdala plays an important role in affective states and disorders such as anxiety and depression. The amygdala is also emerging as a neural substrate of pain affect. However, the involvement of the amygdala in the interaction of pain and anxiety remains to be determined. This study tested the hypothesis that CRF1 receptors in the amygdala are critically involved in pain-related anxiety. Anxiety-like behavior was determined in adult male rats using the elevated plus maze (EPM) test. The open-arm preference (ratio of open arm entries to the total number of entries) was measured. Nocifensive behavior was assessed by measuring hindlimb withdrawal thresholds for noxious mechanical stimulation of the knee. Measurements were made in normal rats and in rats with arthritis induced in one knee by intraarticular injections of kaolin/carrageenan. A selective CRF1 receptor antagonist (NBI27914) or vehicle was administered systemically (i.p.) or into the central nucleus of the amygdala (CeA, by microdialysis). The arthritis group showed a decreased preference for the open arms in the EPM and decreased hindlimb withdrawal thresholds. Systemic or intraamygdalar (into the CeA) administration of NBI27914, but not vehicle, inhibited anxiety-like behavior and nocifensive pain responses, nearly reversing the arthritis pain-related changes. This study shows for the first time that CRF1 receptors in the amygdala contribute critically to pain-related anxiety-like behavior and nocifensive responses in a model of arthritic pain. The results are a direct demonstration that the clinically well-documented relationship between pain and anxiety involves the amygdala.
de Miranda, Aline Silva; Rodrigues, David Henrique; Amaral, Débora Cristina Guerra; de Lima Campos, Roberta Dayrell; Cisalpino, Daniel; Vilela, Márcia Carvalho; Lacerda-Queiroz, Norinne; de Souza, Kátia Paulino Ribeiro; Vago, Juliana Priscila; Campos, Marco Antônio; Kroon, Erna Geesien; da Glória de Souza, Danielle; Teixeira, Mauro Martins; Teixeira, Antônio Lúcio; Rachid, Milene Alvarenga
Dengue virus is a human pathogen that may cause meningoencephalitis and other neurological syndromes. The current study investigated anxiety-like behavior and expression of proinflammatory cytokines and pro-apoptotic caspase-3 in the hippocampus of C57BL/6 mice infected with non-adapted Dengue virus 3 genotype I (DENV-3) inoculated intracranially with 4×10(3) (plaque-forming unit) PFU. Anxiety-like behavior was assessed in control and DENV-3 infected mice using the elevated plus maze. The open field test was performed to evaluate locomotor activity. Histopathological changes in CA regions of the hippocampus were assessed by haematoxylin and eosin staining. Immunoreactive and protein levels of cleaved caspase-3 were also analyzed in the hippocampus. The mRNA expression of IL-6 and TNF-α in the hippocampus were estimated by quantitative real time (polymerase chain reaction) PCR. All procedures were conducted on day 5 post-infection. We found that DENV-3 infected mice presented higher levels of anxiety in comparison with controls (p≤0.05). No difference in motor activity was found between groups (p=0.77). The infection was followed by a significant increase of TNF-α and IL-6 mRNA expression in the hippocampus (p≤0.05). Histological analysis demonstrated meningoencephalitis with formation of perivascular cuffs, infiltration of immune cells and loss of neurons at CA regions of hippocampus. Numerous caspase-3 positive neurons were visualized at CA areas in DENV-3 infected mice. Marked increase of cleaved caspase-3 levels were observed after infection. This study described anxiety-like behavior, hippocampal inflammation and neuronal apoptosis associated with DENV-3 infection in the central nervous system.
Randall-Thompson, Jovita F.; Pescatore, Karen A.
Rationale Compounds acting on delta opioid receptors (DOR) modulate anxiety-like behaviors, yet the site of action underlying this effect is unknown. DOR mRNA and protein are expressed in the central nucleus of the amygdala, a region that plays an important role in processing fear, stress, and anxiety. We hypothesized that this brain region may contribute to the modulation of anxiety by DOR drugs. Objective The present study investigated the role of DOR in the central amygdala in anxiety-like behaviors. Methods The selective DOR agonist [D-Pen 2,5]-enkephalin (DPDPE) or antagonist naltrindole was bilaterally microinjected into the central nucleus of the amygdala of adult male Sprague Dawley rats and anxiety-like behaviors were assessed using the elevated plus maze. The effects of DOR agonists on heightened anxiety produced by stress were also investigated. Results Rats injected with DPDPE into the central nucleus of the amygdala demonstrated less anxiety-like behavior, as evidenced by significantly greater number of open-arm entries and time spent in the open arms than controls. Naltrindole administered alone did not affect the duration or number of entries onto the open arms; however, naltrindole pre-treatment blocked the anxiolytic effects produced by DPDPE. Systemic administration of the selective DOR agonist, SNC80, or microinjection of DPDPE into the central amygdala prior to a swim stress blocked the anxiogenic effect produced by the swim stress. Conclusions These findings provide direct evidence that activation of DOR in the central amygdala reduces anxiety-like behavior and suggest that DOR in this area are important for regulating anxious states. PMID:20730419
Moon, Morgan L; Joesting, Jennifer J; Blevins, Neil A; Lawson, Marcus A; Gainey, Stephen J; Towers, Albert E; McNeil, Leslie K; Freund, Gregory G
Inflammation is a recognized antecedent and coincident factor when examining the biology of anxiety. Little is known, however, about how reductions in endogenous anti-inflammatory mediators impact anxiety. Therefore, mood- cognition- and anxiety-associated/like behaviors were examined in IL-4 knock out (KO) mice and wild-type (WT) mice. In comparison to WT mice, IL-4 KO mice demonstrated decreased burrowing and increased social exploration. No differences were seen in forced swim or saccharine preference testing. IL-4 KO mice had similar performance to WT mice in the Morris water maze and during object location and novel object recognition. In the elevated zero-maze, IL-4 KO mice, in comparison to WT mice, demonstrated anxiety-like behavior. Anxiety-like behavior in IL-4 KO mice was not observed, however, during open-field testing. Taken together, these data indicate that IL-4 KO mice display state, but not trait, anxiety suggesting that reductions in endogenous anti-inflammatory bioactives can engender subtypes of anxiety.
Moon, Morgan L.; Joesting, Jennifer J.; Blevins, Neil A.; Lawson, Marcus A.; Gainey, Stephen J.; Towers, Albert E.; McNeil, Leslie K.; Freund, Gregory G.
Inflammation is a recognized antecedent and coincident factor when examining the biology of anxiety. Little is known, however, about how reductions in endogenous anti-inflammatory mediators impact anxiety. Therefore, mood- cognition- and anxiety-associated/like behaviors were examined in IL-4 knock out (KO) mice and wild-type (WT) mice. In comparison to WT mice, IL-4 KO mice demonstrated decreased burrowing and increased social exploration. No differences were seen in forced swim or saccharine preference testing. IL-4 KO mice had similar performance to WT mice in the Morris water maze and during object location and novel object recognition. In the elevated zero-maze, IL-4 KO mice, in comparison to WT mice, demonstrated anxiety-like behavior. Anxiety-like behavior in IL-4 KO mice was not observed, however, during open-field testing. Taken together, these data indicate that IL-4 KO mice display state, but not trait, anxiety suggesting that reductions in endogenous anti-inflammatory bioactives can engender subtypes of anxiety. PMID:25772794
Barrett, Sarah L.; Uljarevic, Mirko; Baker, Emma K.; Richdale, Amanda L.; Jones, Catherine R. G.; Leekam, Susan R.
In two studies we developed and tested a new self-report measure of restricted and repetitive behaviours (RRB) suitable for adults. In Study 1, The Repetitive Behaviours Questionnaire-2 for adults (RBQ-2A) was completed by a sample of 163 neurotypical adults. Principal components analysis revealed two components: Repetitive Motor Behaviours and…
Hurley, A. D.
Background: Psychiatric evaluation of adults with intellectual disability (ID) remains complex because of limitations in verbal abilities, atypical clinical presentation and challenging behaviour. This study examines the clinical presentation of adults with depression compared with bipolar disorder, anxiety disorders and non-psychiatric control…
Jašarević, Eldin; Hecht, Patrick M; Fritsche, Kevin L; Beversdorf, David Q; Geary, David C
Chronic deficiency of dietary docosahexaenoic acid (DHA) during critical developmental windows results in severe deficits in spatial learning, anxiety and hippocampal neuroplasticity that parallel a variety of neuropsychiatric disorders. However, little is known regarding the influence of long-term, multigenerational exposure to dietary DHA enrichment on these same traits. To characterize the potential benefits of multigenerational DHA enrichment, mice were fed a purified 10:1 omega-6/omega-3 diet supplemented with either 0.1% preformed DHA/kg feed weight or 1.0% preformed DHA/kg feed weight through three generations. General locomotor activity, spatial learning, and anxiety-like behavior were assessed in adult male offspring of the third generation. Following behavioral assessments, ventral and dorsal hippocampus was collected for DHA and arachidonic acid (AA) analysis. Animals consuming the 0.1% and 1.0% DHA diet did not differ from control animals for locomotor activity or on performance during acquisition learning, but made fewer errors and showed more stable across-day performance during reversal learning on the spatial task and showed less anxiety-like behavior. Consumption of the DHA-enriched diets increased DHA content in the ventral and dorsal hippocampus in a region-specific manner. DHA content in the dorsal hippocampus predicted performance on the reversal training task. DHA content in the ventral hippocampus was correlated with anxiety-like behavior, but AA content in the dorsal hippocampus was a stronger predictor of this behavior. These results suggest that long-term, multigenerational DHA administration improves performance on some aspects of complex spatial learning, decreases anxiety-like behavior, and that modulation of DHA content in sub-regions of the hippocampus predicts which behaviors are likely to be affected.
McGuire, B. E.; Daly, P.; Smyth, F.
Background: There is currently no published research in Ireland on the health behaviours of adults with an intellectual disability (ID). With an increasing age profile and similar patterns of morbidity to the general population, the ID population would benefit from baseline data from which to establish risk factors. Methods: A questionnaire survey…
Lee, Hyunchan; Noh, Jihyun
Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration.
The combination of reward and potential threat is termed approach/avoidance conflict and elicits specific behaviors, including passive avoidance and behavioral inhibition (BI). Anxiety-relieving drugs reduce these behaviors, and a rich psychological literature has addressed how personality traits dominated by BI predispose for anxiety disorders. Yet, a formal understanding of the cognitive inference and planning processes underlying anxiety-like BI is lacking. Here, we present and empirically test such formalization in the terminology of reinforcement learning. We capitalize on a human computer game in which participants collect sequentially appearing monetary tokens while under threat of virtual “predation.” First, we demonstrate that humans modulate BI according to experienced consequences. This suggests an instrumental implementation of BI generation rather than a Pavlovian mechanism that is agnostic about action outcomes. Second, an internal model that would make BI adaptive is expressed in an independent task that involves no threat. The existence of such internal model is a necessary condition to conclude that BI is under model-based control. These findings relate a plethora of human and nonhuman observations on BI to reinforcement learning theory, and crucially constrain the quest for its neural implementation. PMID:27797550
Bach, Dominik R
The combination of reward and potential threat is termed approach/avoidance conflict and elicits specific behaviors, including passive avoidance and behavioral inhibition (BI). Anxiety-relieving drugs reduce these behaviors, and a rich psychological literature has addressed how personality traits dominated by BI predispose for anxiety disorders. Yet, a formal understanding of the cognitive inference and planning processes underlying anxiety-like BI is lacking. Here, we present and empirically test such formalization in the terminology of reinforcement learning. We capitalize on a human computer game in which participants collect sequentially appearing monetary tokens while under threat of virtual "predation." First, we demonstrate that humans modulate BI according to experienced consequences. This suggests an instrumental implementation of BI generation rather than a Pavlovian mechanism that is agnostic about action outcomes. Second, an internal model that would make BI adaptive is expressed in an independent task that involves no threat. The existence of such internal model is a necessary condition to conclude that BI is under model-based control. These findings relate a plethora of human and nonhuman observations on BI to reinforcement learning theory, and crucially constrain the quest for its neural implementation. (PsycINFO Database Record
Background The increasing number of people living with HIV aged 50 years and older has been recognised around the world yet non-pharmacologic HIV behavioural and cognitive interventions specifically targeted to older adults are limited. Evidence is needed to guide the response to this affected group. Methods We conducted a systematic review of the available published literature in MEDLINE, Embase and the Education Resources Information Center. A search strategy was defined with high sensitivity but low specificity to identify behavioural interventions with outcomes in the areas of treatment adherence, HIV testing uptake, increased HIV knowledge and uptake of prevention measures. Data from relevant articles were extracted into excel. Results Twelve articles were identified all of which originated from the Americas. Eight of the interventions were conducted among older adults living with HIV and four for HIV-negative older adults. Five studies included control groups. Of the included studies, four focused on general knowledge of HIV, three emphasised mental health and coping, two focused on reduced sexual risk behaviour, two on physical status and one on referral for care. Only four of the studies were randomised controlled trials and seven – including all of the studies among HIV-negative older adults – did not include controls at all. A few of the studies conducted statistical testing on small samples of 16 or 11 older adults making inference based on the results difficult. The most relevant study demonstrated that using telephone-based interventions can reduce risky sexual behaviour among older adults with control reporting 3.24 times (95% CI 1.79-5.85) as many occasions of unprotected sex at follow-up as participants. Overall however, few of the articles are sufficiently rigorous to suggest broad replication or to be considered representative and applicable in other settings. Conclusions More evidence is needed on what interventions work among older adults to
Karanges, Emily; Li, Kong M; Motbey, Craig; Callaghan, Paul D; Katsifis, Andrew; McGregor, Iain S
Selective serotonin reuptake inhibitor use is associated with increased risk of suicidal ideation in adolescent humans, yet the neuropharmacological basis of this phenomenon is unknown. Consequently, we examined the behavioural and neurochemical effects of chronic paroxetine (PRX) treatment in adult and adolescent rats. Rats received PRX in their drinking water (target dose 10 mg/kg) for 22 d, during which time they were assessed for depression- and anxiety-like behaviours. Subsequent ex-vivo analyses examined serum PRX concentrations, striatal neurotransmitter content, and regional serotonin and dopamine transporter (SERT, DAT) binding density. After 11-12 d treatment, PRX-treated adolescent rats showed a significant inhibition of social interaction while adults were unaffected. After 19-20 d treatment, adolescents failed to show an antidepressant-like effect of PRX treatment on the forced swim test (FST), while PRX-treated adults showed a typical decrease in immobility and increase in swimming. Two PRX-treated adolescents died unexpectedly after the FST suggesting a compromised response to physical stress. Despite their greater apparent adverse reaction to the drug, adolescents had significantly lower plasma PRX than adults at day 22 of treatment. Chronic PRX treatment had similar effects in adults and adolescents on striatal 5-HT (unchanged relative to controls) and 5-HIAA levels (decreased), while markers of dopaminergic function (DOPAC, HVA, DA turnover) were increased in adults only. SERT density was up-regulated in the amygdala in PRX-treated adolescents only while DAT density in the nucleus accumbens was down-regulated only in PRX-treated adults. These data suggest that the immature rat brain responds differently to PRX and that this might be of use in modelling the atypical response of human adolescents to antidepressants. The age-specific PRX-induced changes in dopaminergic markers and SERT and DAT binding provide clues as to the neural mechanisms
Makena, Nokuthula; Bugarith, Kishor; Russell, Vivienne A
Early life stress increases the risk of developing psychopathology accompanied by reduced cognitive function in later life. Maternal separation induces anxiety-like behaviours and is associated with impaired memory. On the other hand, exercise has been shown to diminish anxiety-like behaviours and improve cognitive function. The effects of maternal separation and exercise on anxiety, memory and hippocampal proteins were investigated in male Sprague-Dawley rats. Maternal separation produced anxiety-like behaviours which were reversed by exercise. Maternal separation also enhanced object location memory which was not affected by exercise. Exercise did, however, increase synaptophysin and phospho-extracellular signal-regulated kinase (p-ERK) in the hippocampus of non-separated rats and this effect was not observed in maternally separated rats. These findings show that maternal separation selectively enhanced n memory and prevented activation of the MAPK/ERK signalling pathway in the adult rat hippocampus.
Bugarith, Kishor; Russell, Vivienne A
Early life stress increases the risk of developing psychopathology accompanied by reduced cognitive function in later life. Maternal separation induces anxiety-like behaviours and is associated with impaired memory. On the other hand, exercise has been shown to diminish anxiety-like behaviours and improve cognitive function. The effects of maternal separation and exercise on anxiety, memory and hippocampal proteins were investigated in male Sprague–Dawley rats. Maternal separation produced anxiety-like behaviours which were reversed by exercise. Maternal separation also enhanced object location memory which was not affected by exercise. Exercise did, however, increase synaptophysin and phospho-extracellular signal-regulated kinase (p-ERK) in the hippocampus of non-separated rats and this effect was not observed in maternally separated rats. These findings show that maternal separation selectively enhanced n memory and prevented activation of the MAPK/ERK signalling pathway in the adult rat hippocampus. PMID:22476924
Salim, Samina; Sarraj, Nada; Taneja, Manish; Saha, Kaustuv; Tejada-Simon, Maria Victoria; Chugh, Gaurav
Recent work has suggested correlation of oxidative stress with anxiety-like behavior. There also is evidence for anxiolytic effects of physical exercise. However, a direct role of oxidative stress in anxiety is not clear and a protective role of physical exercise in oxidative stress-mediated anxiety has never been addressed. In this study, we have utilized rats to test direct involvement of oxidative stress with anxiety-like behavior and have identified oxidative stress mechanisms likely involved in anxiolytic effects of physical exercise. Intraperitoneal injections at non-toxic dose of l-buthionine-(S,R)-sulfoximine (BSO), an agent that increases oxidative stress markers, increased anxiety-like behavior of rats compared to vehicle-treated control rats. Prior 2 weeks treatment with the antioxidant, tempol attenuated BSO-induced anxiety-like behavior of rats suggesting a role of oxidative stress in this phenomenon. Moreover, moderate treadmill exercise prevented BSO-induced anxiety-like behavior of rats and also prevented BSO-mediated increase in oxidative stress markers in serum, urine and brain tissue homogenates from hippocampus, amygdala and locus coeruleus. Thus increasing oxidative stress increases anxiety-like behavior of rats. Moreover, antioxidant or treadmill exercise training both reduce oxidative stress in the rat brain regions implicated in anxiety response and prevent anxiety-like behavior of rats.
Zheng, Yu; Fan, Weidong; Zhang, Xianquan; Dong, Erbo
Exposure to stressful life events during pregnancy exerts profound effects on neurodevelopment and increases the risk for several neurodevelopmental disorders including major depression. The mechanisms underlying the consequences of gestational stress are complex and remain to be elucidated. This study investigated the effects of gestational stress on depressive-like behavior and epigenetic modifications in young adult offspring. Gestational stress was induced by a combination of restraint and 24-hour light disturbance to pregnant dams throughout gestation. Depressive-like and anxiety-like behaviors of young adult offspring were examined. The expression and promoter methylation of brain derived neurotrophic factor (BDNF) were measured using RT-qPCR, Western blot, methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). In addition, the expressions of histone deacetylases (HDACs) and acetylated histone H3 lysine 14 (AcH3K14) were also analyzed. Our results show that offspring from gestational stress dams exhibited depressive-like and anxiety-like behaviors. Biochemically, stress-offspring showed decreased expression of BDNF, increased expression of DNMT1, HDAC1, and HDAC2, and decreased expression of AcH3K14 in the hippocampus as compared to non-stress offspring. Data from MeDIP and ChIP assays revealed an increased methylation as well as decreased binding of AcH3K14 on specific BDNF promoters. Pearson analyses indicated that epigenetic changes induced by gestational stress were correlated with depressive-like and anxiety-like behaviors. These data suggest that gestational stress may be a suitable model for understanding the behavioral and molecular epigenetic changes observed in patients with depression.
Zheng, Yu; Fan, Weidong; Zhang, Xianquan; Dong, Erbo
ABSTRACT Exposure to stressful life events during pregnancy exerts profound effects on neurodevelopment and increases the risk for several neurodevelopmental disorders including major depression. The mechanisms underlying the consequences of gestational stress are complex and remain to be elucidated. This study investigated the effects of gestational stress on depressive-like behavior and epigenetic modifications in young adult offspring. Gestational stress was induced by a combination of restraint and 24-hour light disturbance to pregnant dams throughout gestation. Depressive-like and anxiety-like behaviors of young adult offspring were examined. The expression and promoter methylation of brain derived neurotrophic factor (BDNF) were measured using RT-qPCR, Western blot, methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). In addition, the expressions of histone deacetylases (HDACs) and acetylated histone H3 lysine 14 (AcH3K14) were also analyzed. Our results show that offspring from gestational stress dams exhibited depressive-like and anxiety-like behaviors. Biochemically, stress-offspring showed decreased expression of BDNF, increased expression of DNMT1, HDAC1, and HDAC2, and decreased expression of AcH3K14 in the hippocampus as compared to non-stress offspring. Data from MeDIP and ChIP assays revealed an increased methylation as well as decreased binding of AcH3K14 on specific BDNF promoters. Pearson analyses indicated that epigenetic changes induced by gestational stress were correlated with depressive-like and anxiety-like behaviors. These data suggest that gestational stress may be a suitable model for understanding the behavioral and molecular epigenetic changes observed in patients with depression. PMID:26890656
Márquez, Natalia; Martínez-Harms, Jaime; Vásquez, Rodrigo A.; Mpodozis, Jorge
We evaluated the extent to which manipulation of early olfactory environment can influence social behaviours in the South American Hystricognath rodent Octodon degus. The early olfactory environment of newborn degus was manipulated by scenting all litter members with eucalyptol during the first month of life. The social behaviour of sexually mature animals (5–7 months old) towards conspecifics was then assessed using a y-maze to compare the response of control (naïve) and treated animals to two different olfactory configurations (experiment 1): (i) a non-familiarized conspecific impregnated with eucalyptol (eucalyptol arm) presented against (ii) a non-familiarized unscented conspecific (control arm). In addition, in dyadic encounters, we assessed the behaviour of control and eucalyptol treated animals towards a non-familiarized conspecific scented with eucalyptol (experiment 2). We found that control subjects explored and spent significantly less time in the eucalyptol arm, indicating neophobic behaviours towards the artificially scented conspecific. Treated subjects explored and spent similar time in both arms of the maze, showing the same interest for both olfactory stimuli presented. During dyadic encounters in experiment 2, an interaction effect between early experience and sex was observed. Control males escaped and avoided their scented partner more frequently than eucalyptol treated male subjects and than females. Both groups did not differ in the exploration of their scented partners, suggesting that avoidance within agonistic context does not relate to neophobic behaviours. Our results suggest that the exposure to eucalyptol during early ontogeny decreases evasive behaviours within an agonistic context as a result of olfactory learning. Altogether, these results indicate that olfactory cues learned in early ontogeny can influence olfactory-guided behaviours in adult degus. PMID:25671542
Masoumi-Ardakani, Yaser; Mahmoudvand, Hossein; Mirzaei, Amin; Esmaeilpour, Khadijeh; Ghazvini, Hamed; Khalifeh, Solmaz; Sepehri, Gholamreza
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition which develops in 6-8% of the general population. Current standard pharmacological treatments for PTSD cannot be widely used due to having various side effects. Nowadays, various pharmacological properties have been related to Elettaria cardamomum L. (family of Zingiberaceae). The present study aims to evaluate the efficacy of E. cardamomum methanolic extract on anxiety-like behavior in a rat model of PTSD. Adult male Wistar rats (200-250gr) were used in this study. The rats underwent single prolonged stress (SPS) or control and intraperitoneally received either saline or different dosages (200, 400, and 800mg/kg) of E. cardamomum methanolic extract before and after stress sessions. Moreover, open field, elevated plus-maze, and rotarod tests were used to evaluate locomotion and anxiety-like behavior in the rats. Findings demonstrated that E. Cardamomum methanolic extract, particularly at the dose of 400mg/kg, significantly (P<0.05) improved anxiety-like behavior in a rat model of PTSD, as examined by the open field, elevated plus-maze, and rotarod tests. Administration of E. cardamomum methanolic extract after stress might help to prevent the formation of anxiety-like behavior in the animals. However, further studies are requiredto clarify the exact mechanisms involved.
Lyvers, Michael; Hasking, Penelope; Hani, Riana; Rhodes, Madolyn; Trew, Emily
Motives to drink alcohol are widely thought to be the proximal cognitive factors involved in the decision to consume alcohol beverages. However it has also been argued that the ability to restrain drinking may be a more proximal predictor of drinking behaviour. The current study aimed to examine the relationships between drinking motives, drinking restraint and both alcohol consumption and alcohol-related problems in a sample of young adults. A sample of 221 young adults (aged 17-34 years) completed self-report measures assessing drinking behaviour, motives for drinking and drinking restraint. Multiple regression analyses revealed that coping, enhancement and social motives were related to alcohol consumption and alcohol-related problems, while Cognitive and Emotional Preoccupation with drinking was related to all criterion variables. Further, the relationship between coping motives and drinking behaviour was mediated by preoccupation with drinking. The results are discussed in light of the roles of drinking motives and drinking restraint in risky drinking among young people, and implications for prevention and early intervention are presented.
Blacher, J.; McIntyre, L. L.
Background: This study examined whether behaviour problems and adaptive behaviour of low functioning young adults, and well-being of their families, varied by diagnostic syndrome intellectual disability (ID) only, cerebral palsy, Down syndrome, autism, as well as by cultural group. Methods: Behaviour disorders in young adults with moderate to…
Pignatti, Riccardo; Mori, Ileana; Bertella, Laura; Grugni, Graziano; Giardino, Daniela; Molinari, Enrico
Background: Obsessive-compulsive (O-C) traits, and excessive food intake are well known behavioural manifestations among individuals with Prader-Willi Syndrome (PWS). Other unwanted behaviours are also frequently observed, but they need a more specific investigation, especially in the adult population. Methods: The behaviour of 31 PWS adults was…
Conrad, Kelly L; Louderback, Katherine M; Gessner, Caitlin P; Winder, Danny G
In vulnerable individuals, exposure to stressors can result in chronic disorders such as generalized anxiety disorder (GAD), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). The extended amygdala is critically implicated in mediating acute and chronic stress responsivity and anxiety-like behaviors. The bed nucleus of the stria terminalis (BNST), a subregion of the extended amygdala, serves as a relay of corticolimbic information to the paraventricular nucleus of the hypothalamus (PVN) to directly influence the stress response. To investigate the influence of the corticosteroid milieu and housing conditions on BNST function, adult C57Bl/6J were either acutely or chronically administered corticosterone (CORT, 25mg/kg in sesame oil) or vehicle (sesame oil) or were group housed or socially isolated for 1 day (acute) or 6-8 weeks (chronic). To ascertain whether these stressors could influence anxiety-like behavior, studies were performed using the novel open-field (NOF) and the elevated zero maze (EZM) tests. To investigate potential associated changes in plasticity, alterations in BNST function were assessed using ex vivo extracellular field potential recordings in the (dorsal-lateral) dlBNST and a high frequency stimulus protocol to induce long-term potentiation (LTP). Our results suggest that chronic CORT injections and chronic social isolation housing conditions lead to an increase in anxiety-like behavior on the EZM and NOF. Chronically stressed mice also displayed a parallel blunting of LTP in the dlBNST. Conversely, acute social isolation housing had no effect on anxiety-like behavior but still resulted in a blunting of LTP in the dlBNST. Collectively, our results suggest acute and chronic stressors can have a distinct profile on plasticity in the BNST that is not uniformly associated with an increase in anxiety-like behavior.
Barrett, Sarah L; Uljarević, Mirko; Baker, Emma K; Richdale, Amanda L; Jones, Catherine R G; Leekam, Susan R
In two studies we developed and tested a new self-report measure of restricted and repetitive behaviours (RRB) suitable for adults. In Study 1, The Repetitive Behaviours Questionnaire-2 for adults (RBQ-2A) was completed by a sample of 163 neurotypical adults. Principal components analysis revealed two components: Repetitive Motor Behaviours and Insistence on Sameness. In Study 2, the mean RBQ-2A scores of a group of adults with autism spectrum disorder (ASD; N = 29) were compared to an adult neurotypical group (N = 37). The ASD sample had significantly higher total and subscale scores. These results indicate that the RBQ-2A has utility as a self-report questionnaire measure of RRBs suitable for adults, with potential clinical application.
Santin, L.J.; Bilbao, A.; Pedraza, C.; Matas-Rico, E.; López-Barroso, D.; Castilla-Ortega, E.; Sánchez-López, J.; Riquelme, R.; Varela-Nieto, I.; de la Villa, P.; Suardíaz, M.; Chun, J.; De Fonseca, F. Rodriguez; Estivill-Torrús, G.
Lysophosphatidic acid (LPA) has emerged as a new regulatory molecule in the brain. Recently, some studies have demonstrated a role for this molecule and its LPA1 receptor in the regulation of plasticity and neurogenesis in the adult brain. However, no systematic studies have been conducted to investigate whether the LPA1 receptor is involved in behavior. Here we studied the phenotype of maLPA1–null mice, which bear a targeted deletion at the lpa1 locus, in a battery of tests examining neurologic performance, habituation in exploratory behavior in response to low and mild anxiety environments and spatial memory. MaLPA1-null mutants showed deficits in both olfaction and somesthesis, but not in retinal or auditory functions. Sensorimotor coordination was impaired only in the equilibrium and grasping reflexes. The mice also showed impairments in neuromuscular strength and analgesic response. No additional differences were observed in the rest of the tests used to study sensoriomotor orientation, limb reflexes, and coordinated limb use. At behavioral level, maLPA1-null mice showed an impaired exploration in the open field and increased anxiety-like response when exposed to the elevated plus maze. Furthermore, the mice exhibit impaired spatial memory retention and reduced use of spatial strategies in the Morris water maze. We propose that the LPA1 receptor may play a major role in both spatial memory and response to anxiety-like conditions. PMID:19689455
Bize, Pierre; Diaz, Claris; Lindström, Jan
Knowledge of the relative importance of genetics and behavioural copying is crucial to appraise the evolvability of behavioural consistencies. Yet, genetic and non-genetic factors are often deeply intertwined, and experiments are required to address this issue. We investigated the sources of variation of adult antipredator behaviour in the Alpine swift (Apus melba) by making use of long-term behavioural observations on parents and cross-fostered offspring. By applying an ‘animal model’ approach to observational data, we show that antipredator behaviour of adult Alpine swifts was significantly repeatable over lifetime (r = 0.273) and heritable (h2 = 0.146). Regression models also show that antipredator behaviours differed between colonies and sexes (females were more tame), and varied with the hour and year of capture. By applying a parent–offspring regression approach to 59 offspring that were exchanged as eggs or hatchlings between pairs of nests, we demonstrate that offspring behaved like their biological parents rather than like their foster parents when they were adults themselves. Those findings provide strong evidence that antipredator behaviour of adult Alpine swifts is shaped by genetics and/or pre-hatching maternal effects taking place at conception but not by behavioural copying. PMID:21976691
Brooks, Leah R; Enix, Courtney L; Rich, Samuel C; Magno, Jinno A; Lowry, Christopher A; Tsai, Pei-San
Serotonergic neurons in the dorsal raphe nucleus (DR) are organized in anatomically distinct subregions that form connections with specific brain structures to modulate diverse behaviors, including anxiety-like behavior. It is unclear if the functional heterogeneity of these neurons is coupled to their developmental heterogeneity, and if abnormal development of specific DR serotonergic subregions can permanently impact anxiety circuits and behavior. The goal of this study was to examine if deficiencies in different components of fibroblast growth factor (Fgf) signaling could preferentially impact the development of specific populations of DR serotonergic neurons to alter anxiety-like behavior in adulthood. Wild-type and heterozygous male mice globally hypomorphic for Fgf8, Fgfr1, or both (Fgfr1/Fgf8) were tested in an anxiety-related behavioral battery. Both Fgf8- and Fgfr1/Fgf8-deficient mice display increased anxiety-like behavior as measured in the elevated plus-maze and the open-field tests. Immunohistochemical staining of a serotonergic marker, tryptophan hydroxylase (Tph), revealed reductions in specific populations of serotonergic neurons in the ventral, interfascicular, and ventrolateral/ventrolateral periaqueductal gray subregions of the DR in all Fgf-deficient mice, suggesting a neuroanatomical basis for increased anxiety-like behavior. Overall, this study suggests Fgf signaling selectively modulates the development of different serotonergic neuron subpopulations. Further, it suggests anxiety-like behavior may stem from developmental disruption of these neurons, and individuals with inactivating mutations in Fgf signaling genes may be predisposed to anxiety disorders.
Tu, Wenyu; Cook, Ashley; Scholl, Jamie L.; Mears, Mackenzie; Watt, Michael J.; Renner, Kenneth J.; Forster, Gina L.
Withdrawal from amphetamine is associated with increased anxiety and sensitivity to stressors which are thought to contribute to relapse. Rats undergoing amphetamine withdrawal fail to exhibit stress-induced increases in serotonin (5-HT) release in the ventral hippocampus and show heightened anxiety-like behaviors. Therefore, we tested the hypothesis that reduced 5-HT levels in the ventral hippocampus is a causal mechanism in increasing anxiety-like behaviors during amphetamine withdrawal. First, we tested whether reducing 5-HT levels in the ventral hippocampus directly increases anxiety behavior. Male rats were bilaterally infused with 5,7-DHT into the ventral hippocampus, which produced a 83% decrease ventral hippocampus 5-HT content, and were tested on the elevated plus maze (EPM) for anxiety-like behavior. Reducing ventral hippocampus 5-HT levels decreased the time spent in the open arms of the maze, suggesting diminished ventral hippocampus 5-HT levels increases anxiety-like behavior. Next, we tested whether increasing 5-HT levels in the ventral hippocampus reverses anxiety behavior exhibited by rats undergoing amphetamine withdrawal. Rats were treated daily with either amphetamine (2.5 mg/kg, ip.) or saline for 2 weeks, and at 2 weeks withdrawal, were infused with the selective serotonin reuptake inhibitor paroxetine (0.5 μM) bilaterally into the ventral hippocampus and tested for anxiety-like behavior on the EPM. Rats pre-treated with amphetamine exhibited increased anxiety-like behavior on the EPM. This effect was reversed by ventral hippocampus infusion of paroxetine. Our results suggest that 5-HT levels in the ventral hippocampus is critical for regulating anxiety behavior. Increasing 5-HT levels during withdrawal may be an effective strategy for reducing anxiety-induced drug relapse. PMID:25241066
Gambeta, Eder; Kopruszinski, Caroline Machado; Dos Reis, Renata Cristiane; Zanoveli, Janaina Menezes; Chichorro, Juliana Geremias
Pain and anxiety are commonly experienced by cancer patients and both significantly impair their quality of life. Some authors claim that there is a relationship between pain and anxiety, while others suggest that there is not a direct association. In any case, there is indeed a consensus that anxiety impairs the pain condition beyond be under diagnosed and undertreated in cancer pain patients. Herein we investigated if rats presenting heat hyperalgesia induced by orofacial cancer cell inoculation would display anxiety-like behaviors. In addition, we evaluated if pain blockade would result in alleviation of anxiety behaviors, as well as, if blockade of anxiety would result in pain relief. Orofacial cancer was induced in male Wistar rats by inoculation of Walker-256 cells into the right vibrissal pad. Heat facial hyperalgesia was assessed on day 6 after the inoculation, and on this time point rats were submitted to the elevated plus maze and the light-dark transition tests. The influence of lidocaine and midazolam on heat hyperalgesia and anxiety-like behaviors was assessed. The peak of facial heat hyperalgesia was detected 6 days after cancer cells inoculation, and at this time point, rats exhibited increased anxiety-like behaviors. Local treatment with lidocaine (2%/50μL) caused a marked reduction of heat hyperalgesia, but failed to affect the anxiety-like behaviors, while midazolam (0.5mg/kg, i.p.) treatment failed to change the heat threshold, but induced an anxiolytic-like effect. Altogether, our data demonstrated that rats with orofacial cancer present pain- and anxiety-like behaviors, but brief heat hyperalgesia relief does not affect the anxiety-like behaviors, and vice-versa, in our experimental conditions.
Tu, W; Cook, A; Scholl, J L; Mears, M; Watt, M J; Renner, K J; Forster, G L
Withdrawal from amphetamine is associated with increased anxiety and sensitivity to stressors which are thought to contribute to relapse. Rats undergoing amphetamine withdrawal fail to exhibit stress-induced increases in serotonin (5-HT) release in the ventral hippocampus and show heightened anxiety-like behaviors. Therefore, we tested the hypothesis that reducing 5-HT levels in the ventral hippocampus is a causal mechanism in increasing anxiety-like behaviors during amphetamine withdrawal. First, we tested whether reducing 5-HT levels in the ventral hippocampus directly increases anxiety behavior. Male rats were bilaterally infused with 5,7-dihydroxytryptamine (5,7-DHT) into the ventral hippocampus, which produced a 83% decrease in ventral hippocampus 5-HT content, and were tested on the elevated plus maze (EPM) for anxiety-like behavior. Reducing ventral hippocampus 5-HT levels decreased the time spent in the open arms of the maze, suggesting that diminished ventral hippocampus 5-HT levels increases anxiety-like behavior. Next, we tested whether increasing 5-HT levels in the ventral hippocampus reverses anxiety behavior exhibited by rats undergoing amphetamine withdrawal. Rats were treated daily with either amphetamine (2.5-mg/kg, i.p.) or saline for 2weeks, and at 2weeks withdrawal, were infused with the selective serotonin reuptake inhibitor paroxetine (0.5μM) bilaterally into the ventral hippocampus and tested for anxiety-like behavior on the EPM. Rats pre-treated with amphetamine exhibited increased anxiety-like behavior on the EPM. This effect was reversed by ventral hippocampus infusion of paroxetine. Our results suggest that 5-HT levels in the ventral hippocampus are critical for regulating anxiety behavior. Increasing 5-HT levels during withdrawal may be an effective strategy for reducing anxiety-induced drug relapse.
Hartley, Sigan L.; MacLean, William E.
Background: People with intellectual disabilities are increasingly reaching older adulthood. Little is known about age-related change in the prevalence of challenging behaviours among older adults with intellectual disabilities. Materials and method: The frequency and severity of staff-averse challenging behaviours of 132 older adults with…
Fedotova, Julia; Akulova, Viktoria; Pivina, Svetlana; Dragasek, Jozef; Caprnda, Martin; Kruzliak, Peter
Gonadal hormones have been well-known to affect brain regions known to be involved in the modulation of mood and affective-related behavior. Prenatal stress might alter hypothalamic-pituitary-gonadal axis, it could be a target for development of affective-related disorders in male offspring. The present study was designed to examine an anxiety-like behavior in the adult male offspring with low levels of endogenous androgens delivered from pregnant dams exposed to prenatal stress from gestation day 15 to gestation day 19. The non-stressed and prenatally stressed intact, gonadectomized (GDX) and GDX male offspring treated with oil solvent or testosterone propionate (TP, 0.5 mg/kg, s.c., 14 days, once daily) were used in all experiments. Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the open field test (OFT), respectively. Also, testosterone levels in the blood serum were measured in all experimental groups of offspring. Prenatally stressed GDX offspring demonstrated a significant decrease for time spent into the open arms and increase for time spent into the closed arms as compared to the non-stressed offspring. Administration of TP to the prenatally stressed GDX offspring resulted in a more markedly decrease of the time spent into the open arms and significantly raised the time spent into the closed arms as compared to the non-stressed GDX offspring treated with TP, non-stressed/prenatally stressed GDX offspring. Prenatally stressed GDX offspring showed a significant increase of crossing, rearing, grooming and defecation as compared to the prenatally stressed control offspring. On the contrary, administration of TP to the prenatally stressed GDX offspring significantly decreased crossing behavior, frequency of rearing and grooming behavior as compared to the non-stressed GDX offspring treated with TP, non-stressed/prenatally stressed GDX offspring. Prenatally stressed GDX offspring demonstrated a significant decrease of testosterone levels
Melville, Craig A; Oppewal, Alyt; Schäfer Elinder, Liselotte; Freiberger, Ellen; Guerra-Balic, Myriam; Hilgenkamp, Thessa I M; Einarsson, Ingi; Izquierdo-Gómez, Rocio H; Sansano-Nadal, Oriol; Rintala, Pauli; Cuesta-Vargas, Antonio; Giné-Garriga, Maria
Supporting positive change in lifestyle behaviours is a priority in tackling the health inequalities experienced by adults with intellectual disabilities. In this systematic review, we examine the evidence on the definition, measurement and epidemiology of sedentary behaviour of adults with intellectual disabilities. A systematic literature search of PUBMED, EMBASE, MEDLINE and Google Scholar was performed to identify studies published from 1990 up to October 2015. Nineteen papers met the criteria for inclusion in the systematic review. Many researchers do not distinguish between insufficient physical activity and sedentary behaviour. None of the studies reported the reliability and validity of the methods used to measure sedentary behaviour. Sedentary time, assessed objectively, ranged from 522 to 643min/day: higher than in adults without intellectual disabilities. This first-ever review of sedentary behaviour and intellectual disabilities found that at present the evidence base is weak. Studies calibrating accelerometer data with criterion measures for sedentary behaviour are needed to determine specific cut-off points to measure sedentary behaviour in adults with intellectual disabilities. Researchers should also examine the reliability and validity of using proxy-report questionnaires to measure sedentary behaviour in this group. A better understanding of sedentary behaviour will inform the design of novel interventions to change lifestyle behaviours of adults with intellectual disabilities.
Tran, Steven; Nowicki, Magda; Muraleetharan, Arrujyan; Chatterjee, Diptendu; Gerlai, Robert
Variation among individuals may arise for several reasons, and may have diverse underlying mechanisms. Individual differences have been studied in a variety of species, but recently a new model organism has emerged in this field that offers both sophistication in phenotypical characterization and powerful mechanistic analysis. Recently, zebrafish, one of the favorites of geneticists, have been shown to exhibit consistent individual differences in baseline locomotor activity. In the current study, we further explore this finding and examine whether individual differences in locomotor activity correlate with anxiety-like behavioral measures and with levels of dopamine, serotonin and the metabolites of these neurotransmitters. In addition, we examine whether individual differences in locomotor activity are also associated with reactivity to the locomotor stimulant effects of and neurochemical responses to acute ethanol exposure (30min long, 1% v/v ethanol bath application). Principal component analyses revealed a strong association among anxiety-like responses, locomotor activity, serotonin and dopamine levels. Furthermore, ethanol exposure was found to abolish the locomotion-dependent anxiety-like behavioral and serotonergic responses suggesting that this drug also engages a common underlying pathway. Overall, our results provide support for an important role of the serotonergic system in mediating individual differences in anxiety-like responses and locomotor activity in zebrafish and for a minor modulatory role of the dopaminergic system.
Meyer, Neele; Jenikejew, Julia; Richter, S Helene; Kaiser, Sylvia; Sachser, Norbert
Adolescence has lately been recognized as a key developmental phase during which an individual's behavior can be shaped. In a recent study with male mice varying in the expression of the serotonin transporter, escapable adverse social experiences during adolescence led to decreased anxiety-like behavior and increased exploratory and aggressive behavior compared to throughout beneficial experiences. Since in this study some behavioral tests took place with a delay of one week after the last social experiences have been made, it was not clear whether the observed effects really reflected the consequences of the experienced different social environments. To test this, the present study focused on the direct effects of beneficial and adverse social experiences on aggressiveness and anxiety-like behavior in C57BL/6J mice. In contrast to the previous study, behavioral testing took place immediately after the last social experiences had been made. Interestingly, whereas individuals from an escapable adverse environment showed significantly lower levels of anxiety-like and higher levels of exploratory behavior than animals from a beneficial environment, aggressive behavior was not affected. From this, we conclude that different social experiences during adolescence exert immediate effects on anxiety-like but not aggressive behavior in male mice.
Parent, Alexandre J.; Beaudet, Nicolas; Beaudry, Hélène; Bergeron, Jenny; Bérubé, Patrick; Drolet, Guy; Sarret, Philippe; Gendron, Louis
For many patients, chronic pain is often accompanied, and sometimes amplified, by co-morbidities such as anxiety and depression. Although it represents important challenges, the establishment of appropriate preclinical behavioral models contributes to drug development for treating chronic inflammatory pain and associated psychopathologies. In this study, we investigated whether rats experiencing persistent inflammatory pain induced by intraplantar injection of complete Freund’s adjuvant (CFA) developed anxiety-like behaviors, and whether clinically used analgesic and anxiolytic drugs were able to reverse CFA-induced anxiety-related phenotypes. These behaviors were evaluated over 28 days in both CFA- and saline-treated groups with a variety of behavioral tests. CFA-induced mechanical allodynia resulted in increased anxiety-like behaviors as evidenced by: 1) a significant decrease in percentage of time spent and number of entries in open arms of the elevated-plus maze (EPM), 2) a decrease in number of central squares visited in the open field (OF), and 3) a reduction in active social interactions in the social interaction test (SI). The number of entries in closed arms in the EPM and the distance travelled in the OF used as indicators of locomotor performance did not differ between treatments. Our results also reveal that in CFA-treated rats, acute administration of morphine (3 mg/kg, s.c.) abolished tactile allodynia and anxiety-like behaviors, whereas acute administration of diazepam (1 mg/kg, s.c) solely reversed anxiety-like behaviors. Therefore, pharmacological treatment of anxiety-like behaviors induced by chronic inflammatory pain can be objectively evaluated using multiple behavioral tests. Such a model could help identify/validate alternative potential targets that influence pain and cognitive dimensions of anxiety. PMID:22245257
Parent, Alexandre J; Beaudet, Nicolas; Beaudry, Hélène; Bergeron, Jenny; Bérubé, Patrick; Drolet, Guy; Sarret, Philippe; Gendron, Louis
For many patients, chronic pain is often accompanied, and sometimes amplified, by co-morbidities such as anxiety and depression. Although it represents important challenges, the establishment of appropriate preclinical behavioral models contributes to drug development for treating chronic inflammatory pain and associated psychopathologies. In this study, we investigated whether rats experiencing persistent inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) developed anxiety-like behaviors, and whether clinically used analgesic and anxiolytic drugs were able to reverse CFA-induced anxiety-related phenotypes. These behaviors were evaluated over 28 days in both CFA- and saline-treated groups with a variety of behavioral tests. CFA-induced mechanical allodynia resulted in increased anxiety-like behaviors as evidenced by: (1) a significant decrease in percentage of time spent and number of entries in open arms of the elevated-plus maze (EPM), (2) a decrease in number of central squares visited in the open field (OF), and (3) a reduction in active social interactions in the social interaction test (SI). The number of entries in closed arms in the EPM and the distance traveled in the OF used as indicators of locomotor performance did not differ between treatments. Our results also reveal that in CFA-treated rats, acute administration of morphine (3mg/kg, s.c.) abolished tactile allodynia and anxiety-like behaviors, whereas acute administration of diazepam (1mg/kg, s.c) solely reversed anxiety-like behaviors. Therefore, pharmacological treatment of anxiety-like behaviors induced by chronic inflammatory pain can be objectively evaluated using multiple behavioral tests. Such a model could help identify/validate alternative potential targets that influence pain and cognitive dimensions of anxiety.
Patki, Gaurav; Ali, Quaisar; Pokkunuri, Indira; Asghar, Mohammad; Salim, Samina
Earlier, we have reported that grape powder (GP) treatment prevented pharmacologic and psychological stress-induced anxiety-like behavior and memory impairment in rats. Protective effects of GP were attributed to its antioxidant effects. In this study, we tested the hypothesis that age-associated behavioral and cognitive deficits such as anxiety and memory impairment will be ameliorated with GP treatment. Using a National Institute of Aging recommended rodent model of aging, we examined a potentially protective role of antioxidant-rich GP in age-associated anxiety-like behavior and memory impairment. Male Fischer 344 rats were randomly assigned into 4 groups: young rats (3 months old) provided with tap water or with 15 g/L GP dissolved in tap water for 3 weeks, aged rats (21 months old) provided with tap water or with GP-treated tap water for 3 weeks (AG-GP). Anxiety-like behavior was significantly greater in aged rats compared with young rats, GP-treated young rats, or aged control rats (P < .05). Also, GP treatment prevented age-induced anxiety-like behavior in AG-GP rats (P < .05). Neither short-term nor long-term age-associated memory deficits improved with GP treatment in AG-GP rats. Furthermore, aged rats showed increased level of physiological stress (corticosterone) and increased oxidative stress in the plasma (8-isoprostane) as well as in selected brain areas (protein carbonylation). Grape powder treatment prevented age-induced increase in corticosterone levels and plasma 8-isoprostane levels in aged rats (P < .05), whereas protein carbonylation was recovered in the amygdala region only (P < .05). Grape powder by regulating oxidative stress ameliorates age-induced anxiety-like behavior in rats, whereas age-associated memory deficits seem unaffected with GP treatment.
Freitas, Daniele; Antoniazzi, Caren T D; Segat, Hecson J; Metz, Vinícia Garzella; Vey, Luciana Taschetto; Barcelos, Raquel C S; Duarte, Thiago; Duarte, Marta M M F; Burger, Marilise Escobar
It is well known that events which occur in early life exert a significant influence on brain development, what can be reflected throughout adulthood. This study was carried out in order to assess the influence of neonatal tactile stimulation (TS) on behavioral and morphological responses related to depression-like and anxiety-like behaviors, assessed following the administration of sertraline (SERT), a selective serotonin re-uptake inhibitor (SSRI). Male pups were submitted to daily TS, from postnatal day 8 (PND8) to postnatal day 14 (PND14), for 10 min every day. On PND50, adult animals were submitted to forced swimming training (15 min). On PND51, half of each experimental group (UH and TS) received a single sub-therapeutic dose of sertraline (SER, 0.3mg/kg body weight, i.p.) or its vehicle (C, control group). Thirty minutes after injection, depression-like behaviors were quantified in forced swimming test (FST, for 5 min). On the following day, anxiety-like behaviors were assessed in elevated plus maze (EPM), followed by biochemical assessments. TS per se increased swimming time, decreasing immobility time in FST. Besides, TS per se was able to increase frequency of head dipping and time spent in the open arms of EPM, resulting in decreased anxiety index. In addition, groups exposed to TS showed decreased plasma levels of corticosterone per se. Interestingly, while TS exposure significantly potentiated the antidepressant activity of a subtherapeutic dose of SERT, this drug was able to exacerbate TS-induced anxiolytic activity, as observed in FST and EPM, respectively. Decreased plasma levels of both corticosterone and cortisol in animals exposed to TS and treated with SERT are able to confirm the interesting interaction between this neonatal handling and the antidepressant drug. From our results, we conclude that neonatal TS is able to exert beneficial influence on the ability to cope with stressful situations in adulthood, preventing depression and favorably
Jiang, You-Ming; Li, Xiao-Juan; Meng, Zhen-Zhi; Liu, Yue-Yun; Zhao, Hong-Bo; Li, Na; Yan, Zhi-Yi; Ma, Qing-Yu; Zhang, Han-Ting; Chen, Jia-Xu
Background. Compared with antidepressant activity of Xiaoyaosan, the role of Xiaoyaosan in anxiety has been poorly studied. Objective. To observe the effects of Xiaoyaosan on anxiety-like behavior induced by chronic immobilization stress (CIS) and further explore whether these effects were related to CRF1R signaling. Methods. Adult male SD rats were randomly assigned to five groups (n = 12): the nonstressed control group, vehicle-treated (saline, p.o.) group, Xiaoyaosan-treated (3.854 g/kg, p.o.) group, vehicle-treated (surgery) group, and antalarmin-treated (surgery) group. Artificial cerebrospinal fluid (0.5 μL/side) or CRF1R antagonist antalarmin (125 ng/0.5 μL, 0.5 μL/side) was bilaterally administered into the basolateral amygdala in the surgery groups. Except for the nonstressed control group, the other four groups were exposed to CIS (14 days, 3 h/day) 30 minutes after treatment. On days 15 and 16, all animals were subjected to the elevated plus-maze (EPM) and novelty suppressed feeding (NSF) test. We then examined the expression of CRF1R, pCREB, and BDNF in the amygdala. Results. Chronic pretreatment with Xiaoyaosan or antalarmin significantly reversed elevated anxiety-like behavior and the upregulated level of CRF1R and BDNF in the amygdala of stressed rats. pCREB did not differ significantly among the groups. Conclusions. These results suggest that Xiaoyaosan exerts anxiolytic-like effects in behavioral tests and the effects may be related to CRF1R signaling in the amygdala. PMID:27042185
Gardner, Benjamin; Smith, Lee; Lorencatto, Fabiana; Hamer, Mark; Biddle, Stuart J H
Sedentary behaviour - i.e., low energy-expending waking behaviour while seated or lying down - is a health risk factor, even when controlling for physical activity. This review sought to describe the behaviour change strategies used within interventions that have sought to reduce sedentary behaviour in adults. Studies were identified through existing literature reviews, a systematic database search, and hand-searches of eligible papers. Interventions were categorised as 'very promising', 'quite promising', or 'non-promising' according to observed behaviour changes. Intervention functions and behaviour change techniques were compared across promising and non-promising interventions. Twenty-six eligible studies reported thirty-eight interventions, of which twenty (53%) were worksite-based. Fifteen interventions (39%) were very promising, eight quite promising (21%), and fifteen non-promising (39%). Very or quite promising interventions tended to have targeted sedentary behaviour instead of physical activity. Interventions based on environmental restructuring, persuasion, or education were most promising. Self-monitoring, problem solving, and restructuring the social or physical environment were particularly promising behaviour change techniques. Future sedentary reduction interventions might most fruitfully incorporate environmental modification and self-regulatory skills training. The evidence base is, however, weakened by low-quality evaluation methods; more RCTs, employing no-treatment control groups, and collecting objective data are needed.
Gardner, Benjamin; Smith, Lee; Lorencatto, Fabiana; Hamer, Mark; Biddle, Stuart JH
Sedentary behaviour – i.e., low energy-expending waking behaviour while seated or lying down – is a health risk factor, even when controlling for physical activity. This review sought to describe the behaviour change strategies used within interventions that have sought to reduce sedentary behaviour in adults. Studies were identified through existing literature reviews, a systematic database search, and hand-searches of eligible papers. Interventions were categorised as ‘very promising’, ‘quite promising’, or ‘non-promising’ according to observed behaviour changes. Intervention functions and behaviour change techniques were compared across promising and non-promising interventions. Twenty-six eligible studies reported thirty-eight interventions, of which twenty (53%) were worksite-based. Fifteen interventions (39%) were very promising, eight quite promising (21%), and fifteen non-promising (39%). Very or quite promising interventions tended to have targeted sedentary behaviour instead of physical activity. Interventions based on environmental restructuring, persuasion, or education were most promising. Self-monitoring, problem solving, and restructuring the social or physical environment were particularly promising behaviour change techniques. Future sedentary reduction interventions might most fruitfully incorporate environmental modification and self-regulatory skills training. The evidence base is, however, weakened by low-quality evaluation methods; more RCTs, employing no-treatment control groups, and collecting objective data are needed. PMID:26315814
Roeckner, Alyssa R; Bowling, Alexandra; Butler, Tracy R
Chronic stress during adolescence is related to increased prevalence of anxiety disorders and alcohol use disorders in humans. This phenotype has been consistently recapitulated in animal models with male subjects, but models using female subjects are fewer. The aim of these studies was to test the hypothesis that chronic social instability (CSI) during adolescence engenders increased anxiety-like behavior, increased corticosterone, and greater ethanol intake and/or preference than control groups in male and female rats. A chronic social instability (CSI) procedure was conducted in separate cohorts of female and male adolescent Long Evans rats. CSI included daily social isolation for 1h, and then pair housing with a novel cage mate for 23h until the next 1h isolation period from PND 30-46. Control groups included social stability (SS), chronic isolation (ISO), and acute social instability (aSI). At PND 49-50, anxiety-like behavior was assessed on the elevated plus maze, and on PND 51 tails bloods were obtained for determination of corticosterone (CORT) levels. This was followed by 4weeks of ethanol drinking in a home cage intermittent access ethanol drinking paradigm (PND 55-81 for males, PND 57-83 for females). Planned contrast testing showed that the male CSI group had greater anxiety-like behavior compared controls, but group differences were not apparent for CORT. CSI males had significantly higher levels of ethanol preference during drinking weeks 2-3 compared to all other groups and compared to SS and ISO groups in week 4. For the female cohort, we did not observe consistent group differences in anxiety-like behavior, CORT levels were unexpectedly lower in the ISO group only compared to the other groups, and group differences were not apparent for ethanol intake/preference. In conclusion, chronic stress during adolescence in the form of social instability increases anxiety-like behavior and ethanol preference in male rats, consistent with other models of
Leo, Giuseppina; Guescini, Michele; Genedani, Susanna; Stocchi, Vilberto; Carone, Chiara; Filaferro, Monica; Sisti, Davide; Marcoli, Manuela; Maura, Guido; Cortelli, Pietro; Guidolin, Diego; Fuxe, Kjell; Agnati, Luigi Francesco
Several clinical observations have demonstrated a link between heart rate and anxiety or panic disorders. In these patients, β-adrenergic receptor function was altered. This prompted us to investigate whether the β-adrenergic receptor agonist isoproterenol, at a dose that stimulates peripheral β-adrenergic system but has no effects at the central nervous system, can induce anxiety-like behavior in rats. Moreover, some possible messengers involved in the peripheral to brain communication were investigated. Our results showed that isoproterenol (5 mg kg(-1) i.p.) increased heart rate, evoked anxiety-like behavior, did not result in motor impairments and increased extracellular vesicle content in the blood. Plasma corticosterone level was unmodified as well as vesicular Hsp70 content. Vesicular miR-208 was also unmodified indicating a source of increased extracellular vesicles different from cardiomyocytes. We can hypothesize that peripheral extracellular vesicles might contribute to the β-adrenergic receptor-evoked anxiety-like behavior, acting as peripheral signals in modulating the mental state.
Mohr, Caroline; Tonge, Bruce J.; Taffe, John; Einfeld, Stewart L.
Background: Standardised normative data for checklists of behavioural and emotional disturbance have a demonstrated usefulness for clinicians, researchers, and service providers. Method: The Developmental Behaviour Checklist for Adults (DBC-A) was the instrument used in a large-scale Australian study (n = 1,538) of emotional and behavioural…
Maas, A. P. H. M.; Sinnema, M.; Didden, R.; Maaskant, M. A.; Smits, M. G.; Schrander-Stumpel, C. T. R. M.; Curfs, L. M. G.
Background: Individuals with Prader-Willi syndrome (PWS) are at risk of sleep disturbances, such as excessive daytime sleepiness (EDS) and sleep apnoea, and behavioural problems. Sleep disturbances and their relationship with other variables had not been researched extensively in adults with PWS. Method: Sleep disturbances and behavioural problems…
Bhaumik, S.; Watson, J. M.; Devapriam, J.; Raju, L. B.; Tin, N. N.; Kiani, R.; Talbott, L.; Parker, R.; Moore, L.; Majumdar, S. K.; Ganghadaran, S. K.; Dixon, K.; Gupta, A. Das; Barrett, M.; Tyrer, F.
Background: Aggressive challenging behaviour is common in adults with intellectual disability (ID) in long-term care facilities. The government's commitment to the closure of all facilities in England has led to concerns over how to manage this behaviour in the community. The aim of this study was to assess changes in aggressive challenging…
Oliver, Chris; Kalsy, Sunny; McQuillan, Sharna; Hall, Scott
Background: Informant-based assessment of behavioural change and difference in dementia in Down syndrome can aid diagnosis and inform service delivery. To date few studies have examined the impact of different types of behavioural change. Methods: The Assessment for Adults with Developmental Disabilities (AADS), developed for this study, assesses…
Laskowski, K L; Monk, C T; Polverino, G; Alós, J; Nakayama, S; Staaks, G; Mehner, T; Arlinghaus, R
This study tested for links among behaviour, state and life-history variables as predicted by the pace-of-life hypothesis in adult pike Esox lucius. First, a standardized open-field behavioural assay was developed to assess individual behaviour of wild-captured adult E. lucius. Behaviour within the standardized assay predicted swimming behaviour in the lake, providing an ecological validation of the assay. There was no relationship between standardized behaviour and any of the life-history and state variables, including metabolism, body condition, juvenile growth rate and adult growth rate in contrast to predictions from the pace-of-life hypothesis. This study demonstrates that it is possible to assess ecologically relevant behavioural variation in a large-bodied top predator using a standard open-field assay, but it is noteworthy that this standardized behaviour is not systematically related to standard metabolism or growth.
Background: Studies of people with intellectual disability suggest that several individual characteristics and environmental factors are associated with behaviour disorder. To date there are few studies looking at risk factors within specific syndromes and the relationship between early risk markers and later behaviour disorder. The key aim of the…
Fraga, Mabel Carneiro; de Moura, Egberto Gaspar; da Silva Lima, Natália; Lisboa, Patrícia C; de Oliveira, Elaine; Silva, Juliana Oliveira; Claudio-Neto, Sylvio; Filgueiras, Cláudio C; Abreu-Villaça, Yael; Manhães, Alex C
The most frequently used animal models of early weaning (EW) in rodents, maternal deprivation and pharmacological inhibition of lactation, present confounding factors, such as high stress or drug side effects, that can mask or interact with the effects of milk deprivation per se. Given these limitations, the development of new models of EW may provide useful information regarding the impact of a shortened period of breastfeeding on the endocrine and nervous systems, both during development and at adulthood. Using a model of EW in which lactating Wistar rat dams are wrapped with a bandage to block access to milk during the last three days of lactation, we have recently shown that the adult offspring presented higher body mass, hyperphagia, hyperleptinemia, leptin as well as insulin resistance, and higher adrenal catecholamine content at adulthood. Here, we used this EW model, which involves no pharmacological treatment or maternal separation, to analyze anxiety-like, novelty-seeking and memory/learning behavioral traits in the adult male offspring. To that end, animals were tested in the elevated plus maze, in the hole board arena and in the radial arm water maze. Except for an increased number of rearing events (a measure of vertical activity), no other behavioral differences were observed between EW and control animals. The contrasting behavioral results between the three EW models may be associated with differences in HPA axis function in the offspring at weaning, since it has been observed that bandaging does not affect corticosteronemia while maternal separation and pharmacological EW increase it.
Cooper, S.-A.; Smiley, E.; Jackson, A.; Finlayson, J.; Allan, L.; Mantry, D.; Morrison, J.
Introduction: Aggressive behaviours can be disabling for adults with intellectual disabilities (ID), with negative consequences for the adult, their family and paid carers. It is surprising how little research has been conducted into the epidemiology of these needs, given the impact they can have. This study investigates point prevalence, 2-year…
Langdon, Jody; Johnson, Chad; Melton, Bridget
Objective: To identify the influence of parental autonomy support, basic need satisfaction and motivation on emerging adults' physical activity level and exercise behaviours. Design: Cross-sectional survey. Setting: This study convenience-sampled approximately 435 college students identified as emerging adults--aged 18-25 years, who did not have a…
McMurray, K M J; Du, X; Brownlee, M; Palmer, A A
GLO1 (Glyoxalase1) is a ubiquitous cellular enzyme that detoxifies methylglyoxal (MG), which is a byproduct of glycolysis. Previously, we showed that ubiquitous overexpression of Glo1 reduced concentrations of MG and increased anxiety-like behavior, whereas systemic injection of MG reduced anxiety-like behavior. We further showed that MG is a competitive partial agonist at GABA-A receptors. Based on those data we hypothesized that modulation of GABAergic signaling by MG underlies Glo1 and MG's effects on anxiety-like behavior. As previous studies used ubiquitous overexpression, we sought to determine whether neuronal Glo1 overexpression was sufficient to increase anxiety-like behavior. We generated ROSA26 knock-in mice with a floxed-stop codon upstream from human Glo1 (FLOXGlo1KI) and bred them with mice expressing CRE recombinase under the direction of the Synapsin 1 promoter (Syn-CRE) to limit overexpression of Glo1 specifically to neurons. Furthermore, since previous administration of MG had been systemic, we sought to determine if direct microinjection of MG into the basolateral amygdala (BLA) was sufficient to reduce anxiety-like behavior. Thus, we performed bilateral microinjections of saline, MG (12μM or 24μM), or the positive control midazolam (4mM) directly into the BLA. FLOXGlo1KIxSyn-CRE mice showed significantly increased anxiety-like behavior compared to their FLOXGLO1xWT littermates. In addition, bilateral microinjection of MG and midazolam significantly decreased anxiety-like behavior compared to saline treated mice. These studies suggest that anatomically specific manipulations of Glo1 and MG are sufficient to induce changes in anxiety-like behavior.
Skelly, M J; Chappell, A E; Carter, E; Weiner, J L
Alcohol use disorder, anxiety disorders, and post-traumatic stress disorder (PTSD) are highly comorbid, and exposure to chronic stress during adolescence may increase the incidence of these conditions in adulthood. Efforts to identify the common stress-related mechanisms driving these disorders have been hampered, in part, by a lack of reliable preclinical models that replicate their comorbid symptomatology. Prior work by us, and others, has shown that adolescent social isolation increases anxiety-like behaviors and voluntary ethanol consumption in adult male Long-Evans rats. Here we examined whether social isolation also produces deficiencies in extinction of conditioned fear, a hallmark symptom of PTSD. Additionally, as disrupted noradrenergic signaling may contribute to alcoholism, we examined the effect of anxiolytic medications that target noradrenergic signaling on ethanol intake following adolescent social isolation. Our results confirm and extend previous findings that adolescent social isolation increases anxiety-like behavior and enhances ethanol intake and preference in adulthood. Additionally, social isolation is associated with a significant deficit in the extinction of conditioned fear and a marked increase in the ability of noradrenergic therapeutics to decrease ethanol intake. These results suggest that adolescent social isolation not only leads to persistent increases in anxiety-like behaviors and ethanol consumption, but also disrupts fear extinction, and as such may be a useful preclinical model of stress-related psychopathology. Our data also suggest that disrupted noradrenergic signaling may contribute to escalated ethanol drinking following social isolation, thus further highlighting the potential utility of noradrenergic therapeutics in treating the deleterious behavioral sequelae associated with early life stress.
Logan, Ryan; Wynne, Olivia; Maglakelidze, George; Zhang, Changqing; O’Connell, Stephanie; Boyadjieva, Nadka I.; Sarkar, Dipak K.
Background Alcohol exposure has adverse effects on stress physiology and behavioral reactivity. This is suggested to be due, in part, to the effect of alcohol on β-endorphin (β-EP) producing neurons in the hypothalamus. In response to stress, β-EP normally provides negative feedback to the HPA axis and interacts with other neurotransmitter systems in the amygdala to regulate behavior. We examined whether β-EP neuronal function in the hypothalamus reduces the corticosterone response to acute stress, attenuates anxiety-like behaviors, and modulates alcohol drinking in rats. Methods To determine if β-EP neuronal transplants modulate the stress response, anxiety behavior and alcohol drinking, we implanted differentiated β-EP neurons into the paraventricular nucleus of the hypothalamus (PVN) of normal, prenatal alcohol exposed, and alcohol-preferring (P) and non-preferring (NP) rats. We then assessed corticosterone levels in response to acute restraint stress and other markers of stress response in the brain, and anxiety-like behaviors in the elevated plus maze and open-field assays. Results We showed that β-EP neuronal transplants into the PVN reduced the peripheral corticosterone response to acute stress and attenuated anxiety-like behaviors. Similar transplants completely reduced the hyper-corticosterone response and elevated anxiety behaviors in prenatal alcohol exposed adult rats. Moreover, we showed that β-EP reduced anxiety behavior in P rats with minimal effects on alcohol drinking during and following restraint stress. Conclusions These data further establish a role of β-EP neurons in the hypothalamus for regulating physiological stress response and anxiety behavior, and resembles a potential novel therapy for treating stress-related psychiatric disorders in prenatal alcohol exposed children and those genetically predisposed to increased alcohol consumption. PMID:25623413
Lim, Lee Wei; Shrestha, Smeeta; Or, Yu Zuan; Tan, Shawn Zheng Kai; Chung, Hwa Hwa; Sun, Yang; Lim, Chew Leng; Khairuddin, Sharafuddin; Lufkin, Thomas; Lin, Valerie Chun Ling
Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in the brain. Previous studies in TTC9A knockout (TTC9A−/−) mice have indicated that TTC9A negatively regulates the action of estrogen. In this study we investigated the role of TTC9A on anxiety-like behavior through its functional interaction with estrogen using the TTC9A−/− mice model. A battery of tests on anxiety-related behaviors was conducted. Our results demonstrated that TTC9A−/− mice exhibited an increase in anxiety-like behaviors compared to the wild type TTC9A+/+ mice. This difference was abolished after ovariectomy, and administration of 17-β-estradiol benzoate (EB) restored this escalated anxiety-like behavior in TTC9A−/− mice. Since serotonin is well-known to be the key neuromodulator involved in anxiety behaviors, the mRNA levels of tryptophan hydroxylase (TPH) 1, TPH2 (both are involved in serotonin synthesis), and serotonin transporter (5-HTT) were measured in the ventromedial prefrontal cortex (vmPFC) and dorsal raphe nucleus (DRN). Interestingly, the heightened anxiety in TTC9A−/− mice under EB influence is consistent with a greater induction of TPH 2, and 5-HTT by EB in DRN that play key roles in emotion regulation. In conclusion, our data indicate that TTC9A modulates the anxiety-related behaviors through modulation of estrogen action on the serotonergic system in the DRN. PMID:27869229
Meirsman, Aura Carole; Robé, Anne
Abstract GPR88 is an orphan G-protein-coupled receptor highly expressed in striatal dopamine D1 (receptor) R- and D2R-expressing medium spiny neurons. This receptor is involved in activity and motor responses, and we previously showed that this receptor also regulates anxiety-like behaviors. To determine whether GPR88 in D2R-expressing neurons contributes to this emotional phenotype, we generated conditional Gpr88 knock-out mice using adenosine A2AR (A2AR)-Cre-driven recombination, and compared anxiety-related responses in both total and A2AR-Gpr88 KO mice. A2AR-Gpr88 KO mice showed a selective reduction of Gpr88 mRNA in D2R-expressing, but not D1R-expressing, neurons. These mutant mice showed increased locomotor activity and decreased anxiety-like behaviors in light/dark and elevated plus maze tests. These phenotypes were superimposable on those observed in total Gpr88 KO mice, demonstrating that the previously reported anxiogenic activity of GPR88 operates at the level of A2AR-expressing neurons. Further, A2AR-Gpr88 KO mice showed no change in novelty preference and novelty-suppressed feeding, while these responses were increased and decreased, respectively, in the total Gpr88 KO mice. Also, A2AR-Gpr88 KO mice showed intact fear conditioning, while the fear responses were decreased in total Gpr88 KO. We therefore also show for the first time that GPR88 activity regulates approach behaviors and conditional fear; however, these behaviors do not seem mediated by receptors in A2AR neurons. We conclude that Gpr88 expressed in A2AR neurons enhances ethological anxiety-like behaviors without affecting conflict anxiety and fear responses. PMID:27570825
Rodriguiz, Ramona M.; Wilkins, John J.; Creson, Thomas K.; Biswas, Reeta; Berezniuk, Iryna; Fricker, Arun D.; Fricker, Lloyd D.; Wetsel, William C.
Cpefat/fat mice have a point mutation in carboxypeptidase E (CPE), an exopeptidase that removes C-terminal basic amino acids from intermediates to produce bioactive peptides. The mutation renders the enzyme inactive and unstable. The absence of CPE activity in these mutants leads to abnormal processing of many peptides, with elevated levels of intermediates and greatly reduced levels of the mature peptides. Cpefat/fat mice develop obesity, diabetes, and infertility in adulthood. We examined whether anxiety- and/or depressive-like behaviors are also present. Anxiety-like responses are not evident in young Cpefat/fat mice (~60 days), but appear in older animals (>90 days). These behaviors are reversed by acute treatment with diazepam or fluoxetine. By contrast, increased immobilities in forced swim and tail suspension are evident in all age groups examined. These behaviors are reversed by acute administration of reboxetine. By comparison acute treatments with fluoxetine or bupropion are ineffective; however, immobility times are normalized with 2 wks of treatment. These data demonstrate that Cpefat/fat mice display depressive-like responses at ~60 days of age, whereas anxiety-like behaviors emerge ~1 month later. In tail suspension, the reboxetine findings show that noradrenergic actions of antidepressants are intact in Cpefat/fat mice. The ability of acute fluoxetine treatment to rescue anxiety-like while leaving depressive-like responses unaffected suggests that serotonin mechanisms underlying these behaviors are different. Since depressive-like responses in the Cpefat/fat mice are rescued by a 2 wk, but not acute, treatment with fluoxetine or buproprion, these mice may serve as a useful model that resembles human depression. PMID:23442571
Suzuki, Satoshi; Saitoh, Akiyoshi; Ohashi, Masanori; Yamada, Misa; Oka, Jun-Ichiro; Yamada, Mitsuhiko
The medial prefrontal cortex is a heterogeneous cortical structure composed of several nuclei, including the prelimbic (PL) and infralimbic (IL) cortices. We previously demonstrated in mice that PL activation with the sodium channel activator veratrine induces anxiety-like behaviors. However, the role of IL in the regulation of anxiety-like behaviors remained unclear. Therefore, in the present study, we investigated the role of the IL in the regulation of anxiety-like behaviors using pharmacological activation model with veratrine, and compared it with the role of the PL. Extracellular glutamate levels were measured by in vivo microdialysis-HPLC with an electrochemical detector, and behaviors were assessed using the open field test. In this study, extracellular glutamate levels rose significantly after perfusion of veratrine in the IL and PL. Interestingly, the PL activation produced anxiety-like behaviors, whereas the activation of the IL produced no anxiety-like behavior in mice. Although the IL is adjacent to the PL, these two regions of the brain have differential functions in the expression of anxiety-like behaviors.
Bevc, Irene; Duchesne, Thierry; Rosenthal, Jeffrey; Rossman, Lianne; Theodor, Frances; Sowa, Edward
This longitudinal study of 248 male offenders examined the relationship between psychiatric disorders, diagnosed in adolescence, and subsequent adult criminal activity. Criminal offences were tracked for an average of 8.7 years from age 18-33. Cox Proportional Intensity regression analyses were conducted to predict the rates of adult offending of…
Schuster, Andrea C.; Carl, Teresa; Foerster, Katharina
Knowledge on animal personality has provided new insights into evolutionary biology and animal ecology, as behavioural types have been shown to affect fitness. Animal personality is characterized by repeatable and consistent between-individual behavioural differences throughout time and across different situations. Behavioural repeatability within life history stages and consistency between life history stages should be checked for the independence of sex and age, as recent data have shown that males and females in some species may differ in the repeatability of behavioural traits, as well as in their consistency. We measured the repeatability and consistency of three behavioural and one cognitive traits in juvenile and adult Eurasian harvest mice ( Micromys minutus). We found that exploration, activity and boldness were repeatable in juveniles and adults. Spatial recognition measured in a Y Maze was only repeatable in adult mice. Exploration, activity and boldness were consistent before and after maturation, as well as before and after first sexual contact. Data on spatial recognition provided little evidence for consistency. Further, we found some evidence for a litter effect on behaviours by comparing different linear mixed models. We concluded that harvest mice express animal personality traits as behaviours were repeatable across sexes and consistent across life history stages. The tested cognitive trait showed low repeatability and was less consistent across life history stages. Given the rising interest in individual variation in cognitive performance, and in its relationship to animal personality, we suggest that it is important to gather more data on the repeatability and consistency of cognitive traits.
Puschban, Zoe; Sah, Anupam; Grutsch, Isabella; Singewald, Nicolas; Dechant, Georg
The presence of the p75 neurotrophin receptor (p75NTR) in adult basal forebrain cholinergic neurons, precursor cells in the subventricular cell layer and the subgranular cell layer of the hippocampus has been linked to alterations in learning as well as anxiety- and depression- related behaviors. In contrast to previous studies performed in a p75NTRexon III−/− model still expressing the short isoform of the p75NTR, we focused on locomotor and anxiety–associated behavior in p75NTRexon IV−/− mice lacking both p75NTR isoforms. Comparing p75NTRexon IV−/− and wildtype mice for both male and female animals showed an anxiolytic-like behavior as evidenced by increased central activities in the open field paradigm and flex field activity system as well as higher numbers of open arm entries in the elevated plus maze test in female p75NTR knockout mice. Morphometrical analyses of dorsal and ventral hippocampus revealed a reduction of width of the dentate gyrus and the granular cell layer in the dorsal but not ventral hippocampus in male and female p75NTRexon IV−/− mice. We conclude that germ-line deletion of p75NTR seems to differentially affect morphometry of dorsal and ventral dentate gyrus and that p75NTR may play a role in anxiety-like behavior, specifically in female mice. PMID:27313517
Mount, R.; Oliver, C.; Berg, K.; Horsler, K.
Background: Individuals with Angelman syndrome appear strongly motivated by social contact, but there have been few studies that have examined the relationship between sociability and familiarity. In this study we compared social behaviour in Angelman syndrome when in contact with mothers and strangers. Methods: We systematically manipulated adult…
Children's interest in exploration is the hallmark of their curiosity. As people who are significant in organising children's environment, how teachers and parents respond to children's exploratory behaviours may promote or hinder the child's desire for further investigation. With reference to Kurt Lewin's concept of "total situation",…
Nergård-Nilssen, Trude; Hulme, Charles
This paper explores the nature of residual literacy and cognitive deficits in self-reported dyslexic Norwegian adults. The performance of 26 self-reported dyslexic adults was compared with that of a comparison group of 47 adults with no history of reading or spelling difficulties. Participants completed standardized and experimental measures tapping literacy skills, working memory, phonological awareness and rapid naming. Spelling problems were the most prominent marker of dyslexia in adults, followed by text reading fluency and nonword decoding. Working memory and phoneme awareness explained unique variance in spelling, whereas rapid automatized naming explained unique variance in reading fluency and nonword reading. The moderate to strong correlations between self-reported history, self-rating of current literacy skills and outcomes on literacy tests indicate that adults estimated their literacy skills fairly well. Results suggest that spelling impairments, more strongly than reading impairments, make adults perceive themselves as being dyslexic. A combination of three literacy and three cognitive tests predicted group membership with 90.4% accuracy. It appears that weaknesses in phoneme awareness, rapid automatized naming and working memory are strong and persistent correlates of literacy problems even in adults learning a relatively transparent orthography.
Rasmussen, Skye; Miller, Melinda M.; Filipski, Sarah B.; Tolwani, Ravi J.
Environmental variables and husbandry practices can influence physiology and alter behavior in mice. Our study evaluated the effects of cage change on serum corticosterone levels and anxiety-like behaviors in C57BL/6 male mice. We examined the effects of 3 different methods of performing cage transfer and of transferring mice to a clean or a dirty familiar cage microenvironment. The 3 different handling methods were forceps transfer, gentle transfer with gloved hands, and a passive transfer technique that did not involve active handling. Active handling methods and transfer to both clean and dirty cage microenvironments significantly increased serum corticosterone 15 min after cage change; however, at 60 min after cage change, levels were comparable to those of unmanipulated mice. Although the effects were transient, cage change altered anxiety-like behaviors in the open field when behavioral testing was performed on the same day. These results demonstrate that the timing of cage change can influence behavioral results, an effect that is an important consideration for rodent behavioral studies. PMID:21838975
Ponzio, Marina F; Monfort, Steven L; Busso, Juan Manuel; Carlini, Valeria P; Ruiz, Rubén D; Fiol de Cuneo, Marta
Due to its complexity, in combination with a lack of scientific reports, fur-chewing became one of the most challenging behavioral problems common to captive chinchillas. In the last years, the hypothesis that fur-chewing is an abnormal repetitive behavior and that stress plays a role in its development and performance has arisen. Here, we investigated whether a relationship existed between the expression and intensity of fur-chewing behavior, elevated urinary cortisol excretion and anxiety-related behaviors. Specifically, we evaluated the following parameters in behaviorally normal and fur-chewing animals of both sexes: (1) mean concentrations of urinary cortisol metabolites and (2) anxiety-like behavior in an elevated plus-maze test. Urinary cortisol metabolites were higher only in females that expressed the most severe form of the fur-chewing behavior (P≤0.05). Likewise, only fur-chewing females exhibited increased (P≤0.05) anxiety-like behaviors associated with the elevated plus-maze test. Overall, these data provided additional evidence to support the concept that fur-chewing is a manifestation of physiological stress in chinchilla, and that a female sex bias exists in the development of this abnormal behavior.
Moon, Morgan L.; Joesting, Jennifer J.; Lawson, Marcus A.; Chiu, Gabriel S.; Blevins, Neil A.; Kwakwa, Kristin A.; Freund, Gregory G.
Objectives Excess fat in the diet can impact neuropsychiatric functions by negatively affecting cognition, mood and anxiety. We sought to show that the free fatty acid (FFA), palmitic acid, can cause adverse biobehaviors in mice that lasts beyond an acute elevation in plasma FFAs. Methods Mice were administered palmitic acid or vehicle as a single intraperitoneal (IP) injection. Biobehaviors were profiled 2 and 24 hrs after palmitic acid treatment. Quantification of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their major metabolites was performed in cortex, hippocampus and amygdala. FFA concentration was determined in plasma. Relative fold change in mRNA expression of unfolded protein response (UPR)-associated genes was determined in brain regions. Results In a dose-dependent fashion, palmitic acid rapidly reduced mouse locomotor activity by a mechanism that did not rely on TLR4, MyD88, IL-1, IL-6 or TNFα but was dependent on fatty acid chain length. Twenty-four hrs after palmitic acid administration mice exhibited anxiety-like behavior without impairment in locomotion, food intake, depressive-like behavior or spatial memory. Additionally, the serotonin metabolite 5-HIAA was increased by 33% in the amygdala 24 hrs after palmitic acid treatment. Conclusions Palmitic acid induces anxiety-like behavior in mice while increasing amygdala-based serotonin metabolism. These effects occur at a time point when plasma FFA levels are no longer elevated. PMID:25016520
Jung, M E; Wallis, C J; Gatch, M B; Lal, H
This study investigated the effects of a benzodiazepine partial agonist, abecarnil, and a full agonist, alprazolam, on ethanol withdrawal-induced anxiety-like behaviors in rats. Anxiety was assessed in two models: elevated plus maze and pentylenetetrazol (GABA(A) antagonist) discrimination assay. Male rats received an ethanol-containing (4.5%) liquid diet for 7 to 10 days and were tested for withdrawal symptoms 12 h after termination of the diet. In the elevated plus maze, ethanol-withdrawn rats displayed less open arm activity and total arm entries than pair-fed rats. Abecarnil (0.08-0.32 mg/kg, IP) and alprazolam (0.08-1.25 mg/kg, IP) each produced a dose-dependent, full reversal of ethanol withdrawal-induced reduction of open arm activity, but only alprazolam increased the total arm entries. In the pentylenetetrazol assay, ethanol-withdrawn rats selected the pentylenetetrazol lever (100%) over the salin-lever. Abecarnil (0.04-0.32 mg/kg, IP) and alprazolam (0.08-0.32 mg/kg, IP) dose dependently reduced pentylenetetrazol-lever responding to control levels (10-20%). Alprazolam was more potent than abecarnil in reversing ethanol withdrawal-induced decrease in open arm activities, but showed comparable potency and efficacy to abecarnil in blocking the pentylenetetrazol-like ethanol withdrawal stimulus. These results suggest that abecarnil and alprazolam may have therapeutic potential for treatment of ethanol withdrawal-induced anxiety-like symptoms.
Imre, István; Di Rocco, Richard; Belanger, Cowan; Brown, Grant; Johnson, Nicholas S.
Using semi-natural enclosures, this study investigated (1) whether adult sea lamprey Petromyzon marinus show avoidance of damage-released conspecific cues, damage-released heterospecific cues and predator cues and (2) whether this is a general response to injured heterospecific fishes or a specific response to injured P. marinus. Ten replicate groups of 10 adult P. marinus, separated by sex, were exposed to one of the following nine stimuli: deionized water (control), extracts prepared from adult P. marinus, decayed adult P. marinus (conspecific stimuli), sympatric white sucker Catostomus commersonii, Amazon sailfin catfish Pterygoplichthys pardalis (heterospecific stimuli), 2-phenylethylamine (PEA HCl) solution, northern water snake Nerodia sipedon washing, human saliva (predator cues) and an adult P. marinus extract and human saliva combination (a damage-released conspecific cue and a predator cue). Adult P. marinus showed a significant avoidance response to the adult P. marinus extract as well as to C. commersonii, human saliva, PEA and the adult P. marinus extract and human saliva combination. For mobile P. marinus, the N. sipedon washing induced behaviour consistent with predator inspection. Exposure to the P. pardalis extract did not induce a significant avoidance response during the stimulus release period. Mobile adult female P. marinus showed a stronger avoidance behaviour than mobile adult male P. marinus in response to the adult P. marinus extract and the adult P. marinus extract and human saliva combination. The findings support the continued investigation of natural damage-released alarm cue and predator-based repellents for the behavioural manipulation of P. marinus populations in the Laurentian Great Lakes.
Imre, I; Di Rocco, R T; Belanger, C F; Brown, G E; Johnson, N S
Using semi-natural enclosures, this study investigated (1) whether adult sea lamprey Petromyzon marinus show avoidance of damage-released conspecific cues, damage-released heterospecific cues and predator cues and (2) whether this is a general response to injured heterospecific fishes or a specific response to injured P. marinus. Ten replicate groups of 10 adult P. marinus, separated by sex, were exposed to one of the following nine stimuli: deionized water (control), extracts prepared from adult P. marinus, decayed adult P. marinus (conspecific stimuli), sympatric white sucker Catostomus commersonii, Amazon sailfin catfish Pterygoplichthys pardalis (heterospecific stimuli), 2-phenylethylamine (PEA HCl) solution, northern water snake Nerodia sipedon washing, human saliva (predator cues) and an adult P. marinus extract and human saliva combination (a damage-released conspecific cue and a predator cue). Adult P. marinus showed a significant avoidance response to the adult P. marinus extract as well as to C. commersonii, human saliva, PEA and the adult P. marinus extract and human saliva combination. For mobile P. marinus, the N. sipedon washing induced behaviour consistent with predator inspection. Exposure to the P. pardalis extract did not induce a significant avoidance response during the stimulus release period. Mobile adult female P. marinus showed a stronger avoidance behaviour than mobile adult male P. marinus in response to the adult P. marinus extract and the adult P. marinus extract and human saliva combination. The findings support the continued investigation of natural damage-released alarm cue and predator-based repellents for the behavioural manipulation of P. marinus populations in the Laurentian Great Lakes.
Damerell, P.; Howe, C.; Milner-Gulland, E. J.
Environmental education is frequently undertaken as a conservation intervention designed to change the attitudes and behaviour of recipients. Much conservation education is aimed at children, with the rationale that children influence the attitudes of their parents, who will consequently change their behaviour. Empirical evidence to substantiate this suggestion is very limited, however. For the first time, we use a controlled trial to assess the influence of wetland-related environmental education on the knowledge of children and their parents and household behaviour. We demonstrate adults exhibiting greater knowledge of wetlands and improved reported household water management behaviour when their child has received wetland-based education at Seychelles wildlife clubs. We distinguish between ‘folk’ knowledge of wetland environments and knowledge obtained from formal education, with intergenerational transmission of each depending on different factors. Our study provides the first strong support for the suggestion that environmental education can be transferred between generations and indirectly induce targeted behavioural changes.
Mezzomo, Nathana J; Silveira, Ariane; Giuliani, Giulie S; Quadros, Vanessa A; Rosemberg, Denis B
Taurine (TAU) is an amino sulfonic acid with several functions in central nervous system. Mounting evidence suggests that it acts in osmoregulation, neuromodulation and also as an inhibitory neurotransmitter. However, the effects of TAU on behavioral functions, especially on anxiety-related parameters, are limited. The adult zebrafish is a suitable model organism to examine anxiety-like behaviors since it presents neurotransmitter systems and behavioral functions evolutionary conserved. Anxiety in zebrafish can be measured by different tasks, analyzing the habituation to novelty, as well as the response to brightly lit environments. The aim of this study was to investigate whether acute TAU treatment alters anxiety-like behavior in zebrafish using the novel tank and the light-dark tests. Fish were individually treated with TAU (42, 150, and 400mg/L) for 1h and the behaviors were further analyzed for 6min in the novel tank or in the light-dark test. Control fish were handled in a similar manner, but kept only in home tank water. Although TAU did not alter locomotor and vertical activities, all concentrations significantly increased shuttling and time spent in lit compartment. Moreover, TAU 150 group showed a significant decrease in the number of risk assessment episodes. Overall, these data suggest that TAU exerts an anxiolytic-like effect in zebrafish and the comparative analysis of behavior using different tasks is an interesting strategy for neuropsychiatric studies related to anxiety in this species.
Huffman, S; Szafron, M
Research on the correlates of sedentary behaviour among adults is needed to design health interventions to modify this behaviour. This study explored the associations of social correlates with leisure-time sedentary behaviour of Canadian adults, and whether these associations differ between different types of sedentary behaviour. A sample of 12,021 Canadian adults was drawn from the 2012 Canadian Community Health Survey, and analyzed using binary logistic regression to model the relationships that marital status, the presence of children in the household, and social support have with overall time spent sitting, using a computer, playing video games, watching television, and reading during leisure time. Covariates included gender, age, education, income, employment status, perceived health, physical activity level, body mass index (BMI), and province or territory of residence. Extensive computer time was primarily negatively related to being in a common law relationship, and primarily positively related to being single/never married. Being single/never married was positively associated with extensive sitting time in men only. Having children under 12 in the household was protective against extensive video game and reading times. Increasing social support was negatively associated with extensive computer time in men and women, while among men increasing social support was positively associated with extensive sitting time. Computer, video game, television, and reading time have unique correlates among Canadian adults. Marital status, the presence of children in the household, and social support should be considered in future analyses of sedentary activities in adults.
Sangenstedt, Susanne; Jaljuli, Iman; Sachser, Norbert; Kaiser, Sylvia
The early social environment can profoundly affect behavioral and physiological phenotypes. We investigated how male wild cavy offspring, whose mothers had either lived in a stable (SE) or an unstable social environment (UE) during pregnancy and lactation, differed in their anxiety-like behavior and stress responsiveness. At two different time points in life, we tested the offspring's anxiety-like behavior in a dark-light test and their endocrine reaction to challenge in a cortisol reactivity test. Furthermore, we analyzed whether individual traits remained stable over time. There was no effect of the early social environment on anxiety-like behavior and stress responsiveness. However, at an individual level, anxiety-like behavior was stable over time in UE- but not in SE-sons. Stress responsiveness, in turn, was rather inconsistent in UE-sons and temporally stable in SE-sons. Conclusively, we showed for the first time that the early social environment differentially shapes the stability of behavioral and endocrine traits. At first glance, these results may be surprising, but they can be explained by the different functions anxiety-like behavior and stress responsiveness have.
Heshmati, Mitra; Golden, Sam A; Pfau, Madeline L; Christoffel, Daniel J; Seeley, Elena L; Cahill, Michael E; Khibnik, Lena A; Russo, Scott J
Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperitoneal injection of mefloquine in mice, when coupled to subthreshold social defeat stress, is sufficient to produce depression-like social avoidance behavior. Direct infusion of mefloquine into the nucleus accumbens (NAc), a key brain reward region, increased stress-induced social avoidance and anxiety behavior. In contrast, infusion into the ventral hippocampus had no effect. Whole cell recordings from NAc medium spiny neurons indicated that mefloquine application increases the frequency of spontaneous excitatory postsynaptic currents, a synaptic adaptation that we have previously shown to be associated with increased susceptibility to social defeat stress. Together, these data demonstrate a role for the NAc in mefloquine-induced depression and anxiety-like behaviors.
Okamoto, Kitaro; Yamasaki, Miwako; Takao, Keizo; Soya, Shingo; Iwasaki, Monica; Sasaki, Koh; Magoori, Kenta; Sakakibara, Iori; Miyakawa, Tsuyoshi; Mieda, Michihiro; Watanabe, Masahiko; Sakai, Juro; Yanagisawa, Masashi; Sakurai, Takeshi
How the hypothalamus transmits hunger information to other brain regions to govern whole brain function to orchestrate feeding behavior has remained largely unknown. Our present study suggests the importance of a recently found lateral hypothalamic neuropeptide, QRFP, in this signaling. Qrfp-/- mice were hypophagic and lean, and exhibited increased anxiety-like behavior, and were hypoactive in novel circumstances as compared with wild type littermates. They also showed decreased wakefulness time in the early hours of the dark period. Histological studies suggested that QRFP neurons receive rich innervations from neurons in the arcuate nucleus which is a primary region for sensing the body’s metabolic state by detecting levels of leptin, ghrelin and glucose. These observations suggest that QRFP is an important mediator that acts as a downstream mediator of the arcuate nucleus and regulates feeding behavior, mood, wakefulness and activity. PMID:27835635
Heshmati, Mitra; Golden, Sam A.; Pfau, Madeline L.; Christoffel, Daniel J.; Seeley, Elena L.; Cahill, Michael E.; Khibnik, Lena A.; Russo, Scott J.
Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperitoneal injection of mefloquine in mice, when coupled to subthreshold social defeat stress, is sufficient to produce depression-like social avoidance behavior. Direct infusion of mefloquine into the nucleus accumbens (NAc), a key brain reward region, increased stress-induced social avoidance and anxiety behavior. In contrast, infusion into the ventral hippocampus had no effect. Whole cell recordings from NAc medium spiny neurons indicated that mefloquine application increases the frequency of spontaneous excitatory postsynaptic currents, a synaptic adaptation that we have previously shown to be associated with increased susceptibility to social defeat stress. Together, these data demonstrate a role for the NAc in mefloquine-induced depression and anxiety-like behaviors. PMID:26471420
Matson, Johnny L.; Boisjoli, Jessica A.
Background: The "Questions About Behavioral Function" (QABF) correctly identifies maintaining variables of challenging behaviour. However, for adults who have a long history of challenging behaviours, identifying one clear function of the maladaptive behaviour is difficult. Additionally, the person may develop multiple functions of their…
Deb, S.; Sohanpal, S. K.; Soni, R.; Lenotre, L.; Unwin, G.
Background: Psychopharmacological intervention in the management of behaviour problems in adults with intellectual disabilities (ID) has become a common treatment strategy. This has become a cause for concern, given that the evidence for its effectiveness is uncertain and most drugs are not licensed for this use. Methods: A comprehensive…
Background Adults spend the majority of their time being sedentary, and evidence suggests that those who spend more of their day engaged in sedentary activities (TV viewing, sitting, screen-based activities) are at increased risk for morbidity and mortality, regardless of whether they exercise regularly. In order to develop effective interventions to reduce sedentary time, it is necessary to identify and understand the strongest modifiable factors of these behaviours. Therefore, the objective of this systematic review is to examine the available evidence in order to identify individual, social, environmental and policy correlates and determinants of sedentary behaviours (TV time, sitting time, screen time) and total sedentary time among adults. Methods/design Six electronic databases will be searched to identify all studies that report on individual, social and/or environmental correlates and determinants of sedentary behaviours and total sedentary time in adults. Grey literature sources including theses, published conference abstracts and websites from relevant organizations will also be included. Articles that report on modifiable individual (e.g. health behaviours and status, self-efficacy, socio-economic status), social (e.g. crime, safety, social support, climate and capital), environmental (e.g. weather, workplace, home, neighbourhood, recreation environment, transportation environment) and policy correlates and determinants (based on study design) of sedentary behaviours in an adult population (mean age ≥18 years) will be included. Study quality and risk of bias will be assessed within and across all included studies. Harvest plots will be used to synthesize results across all correlates, and meta-analyses will be conducted where possible among studies with sufficient homogeneity. Discussion This review will provide a comprehensive examination of evidence in the field and will serve to highlight gaps for future research on the determinants of sedentary
Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P
Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804
Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P
In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central nucleus of the amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BnST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST.
Tyagi, Ethika; Agrawal, Rahul; Zhuang, Yumei; Abad, Catalina; Waschek, James A; Gomez-Pinilla, Fernando
Mild traumatic brain injury (mTBI, cerebral concussion) is a risk factor for the development of psychiatric illness such as posttraumatic stress disorder (PTSD). We sought to evaluate how omega-3 fatty acids during brain maturation can influence challenges incurred during adulthood (transitioning to unhealthy diet and mTBI) and predispose the brain to a PTSD-like pathobiology. Rats exposed to diets enriched or deficient in omega-3 fatty acids (n-3) during their brain maturation period, were transitioned to a western diet (WD) when becoming adult and then subjected to mTBI. TBI resulted in an increase in anxiety-like behavior and its molecular counterpart NPY1R, a hallmark of PTSD, but these effects were more pronounced in the animals exposed to n-3 deficient diet and switched to WD. The n-3 deficiency followed by WD disrupted BDNF signaling and the activation of elements of BDNF signaling pathway (TrkB, CaMKII, Akt and CREB) in frontal cortex. TBI worsened these effects and more prominently in combination with the n-3 deficiency condition. Moreover, the n-3 deficiency primed the immune system to the challenges imposed by the WD and brain trauma as evidenced by results showing that the WD or mTBI affected brain IL1β levels and peripheral Th17 and Treg subsets only in animals previously conditioned to the n-3 deficient diet. These results provide novel evidence for the capacity of maladaptive dietary habits to lower the threshold for neurological disorders in response to challenges.
Moon, Dal-Hyun; Yun, Joonkoo; McNamee, Jeff
The purposes of this study were to examine the effects of varying levels of goals on increasing daily steps and the frequency of goal achievement among middle-aged adults. Ninety-six adults participated in a randomised control study. Participants were randomly assigned to five different step goal groups: (1) Easy (n = 19), (2) Medium (n = 19), (3) Difficult (n = 19), (4) Do-your-best (n = 19), and (5) No goal (n = 20) based on previous research. The participants wore a pedometer and were asked to reach a pre-established goal during the experimental period. In order to examine the effectiveness of the goal difficulty, (a) an average number of steps taken by different goal conditions and (b) the number of days meeting the assigned goal were tested. A one-way ANCOVA revealed significant step count differences among goal groups. Post hoc analyses indicated that the change in step count in both the Medium and Difficult goal groups was significantly greater than the remaining groups. However, there was no significant difference between the medium and difficult goal conditions. In addition, a one-way ANOVA indicated that there were no significant differences in the frequency of goal achievement among the Easy, Medium, and Difficult goal groups. Results suggest that when promoting physical activity through increasing step counts, researchers and clinicians should design goals that are specific and challenging.
Kilner, Rebecca M; Boncoraglio, Giuseppe; Henshaw, Jonathan M; Jarrett, Benjamin JM; De Gasperin, Ornela; Attisano, Alfredo; Kokko, Hanna
The parents' phenotype, or the environment they create for their young, can have long-lasting effects on their offspring, with profound evolutionary consequences. Yet, virtually no work has considered how such parental effects might change the adaptive value of behavioural traits expressed by offspring upon reaching adulthood. To address this problem, we combined experiments on burying beetles (Nicrophorus vespilloides) with theoretical modelling and focussed on one adult behavioural trait in particular: the supply of parental care. We manipulated the early-life environment and measured the fitness payoffs associated with the supply of parental care when larvae reached maturity. We found that (1) adults that received low levels of care as larvae were less successful at raising larger broods and suffered greater mortality as a result: they were low-quality parents. Furthermore, (2) high-quality males that raised offspring with low-quality females subsequently suffered greater mortality than brothers of equivalent quality, which reared larvae with higher quality females. Our analyses identify three general ways in which parental effects can change the adaptive value of an adult behavioural trait: by influencing the associated fitness benefits and costs; by consequently changing the evolutionary outcome of social interactions; and by modifying the evolutionarily stable expression of behavioural traits that are themselves parental effects. DOI: http://dx.doi.org/10.7554/eLife.07340.001 PMID:26393686
Fässberg, Madeleine Mellqvist; Cheung, Gary; Canetto, Silvia Sara; Erlangsen, Annette; Lapierre, Sylvie; Lindner, Reinhard; Draper, Brian; Gallo, Joseph J.; Wong, Christine; Wu, Jing; Duberstein, Paul; Wærn, Margda
Objectives: To conduct a systematic review of studies that examined associations between physical illness/functional disability and suicidal behaviour (including ideation, nonfatal and fatal suicidal behaviour) among individuals aged 65 and older. Method: Articles published through November 2014 were identified through electronic searches using the ERIC, Google Scholar, PsycINFO, PubMed, and Scopus databases. Search terms used were suicid* or death wishes or deliberate self-harm. Studies about suicidal behaviour in individuals aged 65 and older with physical illness/functional disabilities were included in the review. Results: Sixty-five articles (across 61 independent samples) met inclusion criteria. Results from 59 quantitative studies conducted in four continents suggest that suicidal behaviour is associated with functional disability and numerous specific conditions including malignant diseases, neurological disorders, pain, COPD, liver disease, male genital disorders, and arthritis/arthrosis. Six qualitative studies from three continents contextualized these findings, providing insights into the subjective experiences of suicidal individuals. Implications for interventions and future research are discussed. Conclusion: Functional disability, as well as a number of specific physical illnesses, was shown to be associated with suicidal behaviour in older adults. We need to learn more about what at-risk, physically ill patients want, and need, to inform prevention efforts for older adults. PMID:26381843
Lee, Hee Yun; Rhee, Taeho Greg; Kim, Nam Keol
This study investigates the cancer literacy level in Korean adults and examines whether cancer literacy plays a mediating role in the relationship between population characteristics and cancer screening behaviours. We collected data from 585 community-dwelling adults in Korea using self-administered surveys and face-to-face interviews from October to December in 2009. Guided by Andersen's behavioural model, we used a structural equation model to estimate the effect of cancer literacy as a mediator and found that cancer literacy mediated cancer screening behaviour. In the individual path analysis models, cancer literacy played a significant mediating role for the use of eastern medicine, fatalism, health status and the number of chronic diseases. When controlling for other relevant covariates, we found that in the optimal path model, cancer literacy played a mediating role in the relationship between the use of eastern medicine and self-rated health status as well as cancer screening behaviour. Thus, developing community-based cancer education programmes and training clinical practitioners in eastern medicine clinics about the importance of informing their patients about regular cancer screening may be an option to boost cancer literacy and screening behaviour in Korea.
Abdallah, Sara J; Thomas, Benjamin S; Jonz, Michael G
Severe hypoxia elicits aquatic surface respiration (ASR) behaviour in many species of fish, where ventilation of the gills at the air-water interface improves O2 uptake and survival. ASR is an important adaptation that may have given rise to air breathing in vertebrates. The neural substrate of this behaviour, however, is not defined. We characterized ASR in developing and adult zebrafish (Danio rerio) to ascertain a potential role for peripheral chemoreceptors in initiation or modulation of this response. Adult zebrafish exposed to acute, progressive hypoxia (PO2 from 158 to 15 mmHg) performed ASR with a threshold of 30 mmHg, and spent more time at the surface as PO2 decreased. Acclimation to hypoxia attenuated ASR responses. In larvae, ASR behaviour was observed between 5 and 21 days postfertilization with a threshold of 16 mmHg. Zebrafish decreased swimming behaviour (i.e. distance, velocity and acceleration) as PO2 was decreased, with a secondary increase in behaviour near or below threshold PO2 . In adults that underwent a 10-day intraperitoneal injection regime of 10 μg g(-1) serotonin (5-HT) or 20 μg g(-1) acetylcholine (ACh), an acute bout of hypoxia (15 mmHg) increased the time engaged in ASR by 5.5 and 4.9 times, respectively, compared with controls. Larvae previously immersed in 10 μmol l(-1) 5-HT or ACh also displayed an increased ASR response. Our results support the notion that ASR is a behavioural response that is reliant upon input from peripheral O2 chemoreceptors. We discuss implications for the role of chemoreceptors in the evolution of air breathing.
Pagani, Jerome H.; Williams Avram, Sarah K.; Cui, Zhenzhong; Song, June; Mezey, Éva; Senerth, Julia M.; Baumann, Michael H.; Young, W. Scott
Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically-mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to eight of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care. PMID:25677455
Zhang, Qi; Sano, Chie; Masuda, Akira; Ando, Reiko; Tanaka, Mika; Itohara, Shigeyoshi
In vertebrate mammals, distributed neural circuits in the brain are involved in emotion-related behavior. Netrin-G1 is a glycosyl-phosphatidylinositol-anchored synaptic adhesion molecule whose deficiency results in impaired fear-like and anxiety-like behaviors under specific circumstances. To understand the cell type and circuit specificity of these responses, we generated netrin-G1 conditional knockout mice with loss of expression in cortical excitatory neurons, inhibitory neurons, or thalamic neurons. Genetic deletion of netrin-G1 in cortical excitatory neurons resulted in altered anxiety-like behavior, but intact fear-like behavior, whereas loss of netrin-G1 in inhibitory neurons resulted in attenuated fear-like behavior, but intact anxiety-like behavior. These data indicate a remarkable double dissociation of fear-like and anxiety-like behaviors involving netrin-G1 in excitatory and inhibitory neurons, respectively. Our findings support a crucial role for netrin-G1 in dissociable neural circuits for the modulation of emotion-related behaviors, and provide genetic models for investigating the mechanisms underlying the dissociation. The results also suggest the involvement of glycosyl-phosphatidylinositol-anchored synaptic adhesion molecules in the development and pathogenesis of emotion-related behavior. PMID:27345935
Krishnan, Keerthi; Lau, Billy Y. B.; Ewall, Gabrielle; Huang, Z. Josh; Shea, Stephen D.
Neurodevelopmental disorders are marked by inappropriate synaptic connectivity early in life, but how disruption of experience-dependent plasticity contributes to cognitive and behavioural decline in adulthood is unclear. Here we show that pup gathering behaviour and associated auditory cortical plasticity are impaired in female Mecp2het mice, a model of Rett syndrome. In response to learned maternal experience, Mecp2het females exhibited transient changes to cortical inhibitory networks typically associated with limited plasticity. Averting these changes in Mecp2het through genetic or pharmacological manipulations targeting the GABAergic network restored gathering behaviour. We propose that pup gathering learning triggers a transient epoch of inhibitory plasticity in auditory cortex that is dysregulated in Mecp2het. In this window of heightened sensitivity to sensory and social cues, Mecp2 mutations suppress adult plasticity independently from their effects on early development. PMID:28098153
Zhu, Huiwen; Liu, Zhiyuan; Zhou, Yiming; Yin, Xuming; Xu, Bo; Ma, Lan; Liu, Xing
It is well known that β-adrenoceptors (β-ARs) play a critical role in emotional arousal and stressful events, but the specific contributions of the β2-AR subtype to the psychological disorders are largely unknown. To investigate whether β2-AR are involved in anxiety-like behavior and reward to addictive drugs, we conducted a series of behavioral tests on β2-AR knock-out (KO) mice. β2-AR KO mice exhibited increased preference for the dark compartment and closed arm in tests of Light/Dark box and elevated plus maze, indicating that β2-AR deletion elevates level of anxiety or innate fear. β2-AR KO mice also showed decreased immobility in tail suspension test (TST), suggesting that β2-AR deletion inhibits depression-like behavior. Interestingly, β2-AR ablation did not change basal locomotion but significantly increased locomotor activity induced by acute cocaine administration. β2-AR KO mice showed enhanced place preference for cocaine, which could be attenuated by β1-selective AR antagonist betaxolol. Consistently, β2-AR agonist suppressed cocaine-conditioned place preference (CPP). These data indicate that β2-AR deletion enhances acute response and reward to cocaine. Our results suggest that β2-AR regulates anxiety level, depression-like behavior and hedonic properties of cocaine, implicating that β2-AR are the potential targets for the treatment of emotional disorders and cocaine addiction. PMID:28348522
Wang, Yali; Li, Siyue; Liu, Wenwen; Wang, Fen; Hu, Li-Fang; Zhong, Zhao-Min; Wang, Han; Liu, Chun-Feng
Vesicular monoamine transporter 2 (Vmat2) is widely distributed in the central nervous system, and responsible for uptaking transmitters into the vesicles. However, whether Vmat2-deficiency is related to the anxiety is rarely investigated, especially in zebrafish. Here, we reported Vmat2 heterzygous mutant zebrafish displayed anxiety-like behavior. The mutants spent less time in the top area and took longer latency to the top in the novel tank test. Consistently, they showed dark avoidance in the light/dark box test, with longer duration in the light zone and increased number of crossing between the two zones. Monoamine concentration analysis showed that the levels of monoamine neurotransmitters including dopamine (DA), 5-hydroxy tryptamine (5-HT) and norepinephrine (NE), as well as their metabolites were decreased in VMAT mutants. Taken together, these findings suggest that Vmat2 heterzygous mutant zebrafish may serve as a new model of anxiety, which may be related with the low level of DA, 5-HT and NE.
Zhu, Huiwen; Liu, Zhiyuan; Zhou, Yiming; Yin, Xuming; Xu, Bo; Ma, Lan; Liu, Xing
It is well known that β-adrenoceptors (β-ARs) play a critical role in emotional arousal and stressful events, but the specific contributions of the β2-AR subtype to the psychological disorders are largely unknown. To investigate whether β2-AR are involved in anxiety-like behavior and reward to addictive drugs, we conducted a series of behavioral tests on β2-AR knock-out (KO) mice. β2-AR KO mice exhibited increased preference for the dark compartment and closed arm in tests of Light/Dark box and elevated plus maze, indicating that β2-AR deletion elevates level of anxiety or innate fear. β2-AR KO mice also showed decreased immobility in tail suspension test (TST), suggesting that β2-AR deletion inhibits depression-like behavior. Interestingly, β2-AR ablation did not change basal locomotion but significantly increased locomotor activity induced by acute cocaine administration. β2-AR KO mice showed enhanced place preference for cocaine, which could be attenuated by β1-selective AR antagonist betaxolol. Consistently, β2-AR agonist suppressed cocaine-conditioned place preference (CPP). These data indicate that β2-AR deletion enhances acute response and reward to cocaine. Our results suggest that β2-AR regulates anxiety level, depression-like behavior and hedonic properties of cocaine, implicating that β2-AR are the potential targets for the treatment of emotional disorders and cocaine addiction.
Carlini, V P; Ghersi, M; Gabach, L; Schiöth, H B; Pérez, M F; Ramirez, O A; Fiol de Cuneo, M; de Barioglio, S R
A 13-amino acid peptide named neuronostatin (NST) encoded in the somatostatin pro-hormone has been recently reported. It is produced throughout the body, particularly in brain areas that have significant actions over the metabolic and autonomic regulation. The present study was performed in order to elucidate the functional role of NST on memory, anxiety-like behavior and food intake and the hippocampal participation in these effects. When the peptide was intra-hippocampally administered at 3.0 nmol/μl, it impaired memory retention in both, object recognition and step-down test. Also, this dose blocked the hippocampal long-term potentiation (LTP) generation. When NST was intra-hippocampally administered at 0.3 nmol/μl and 3.0 nmol/μl, anxiolytic effects were observed. Also, the administration in the third ventricle at the higher dose (3.0 nmol/μl) induced similar effects, and both doses reduced food intake. The main result of the present study is the relevance of the hippocampal formation in the behavioral effects induced by NST, and these effects could be associated to a reduced hippocampal synaptic plasticity.
Mizunoya, Wataru; Ohnuki, Koichiro; Baba, Kento; Miyahara, Hideo; Shimizu, Naomi; Tabata, Kuniko; Kino, Takako; Sato, Yusuke; Tatsumi, Ryuichi; Ikeuchi, Yoshihide
Dietary fat plays an important role in higher brain functions. We aimed to assess the short and long term intake of three different types of dietary fat (soybean oil, lard, and fish oil) on anxiety-like and depression-like behavior in mice. For the short term intake assessment, a behavioral test battery for anxiety and depression was carried out for a 3-day feeding period. For the long term intake assessment, a behavioral test battery began after the 4-week feeding period. During the short term intake, the time spent in the open arms of the elevated plus-maze was the longest in the fish oil fed group, followed by the soybean oil and lard-fed groups. The elevated plus-maze is a common animal model to assess anxiety, in which an increased time spent in the open arms indicates an anxiolytic effect. The difference between the fish oil-fed group and lard-fed group was statistically significant (p < 0.01), but there was no significant difference between the soybean oil-fed group and the other two groups. Similar results were observed after a 4-week feeding period. On the other hand, there was no significant difference among the three groups in behavior tests to evaluate depression. Thus, the dietary fat types appeared to influence anxiety but not depression in mice, both in short term (3 days) and long term (4 weeks) feeding.
Mascitelli, Andréa N.; Rojahn, Johannes; Nicolaides, Vias C.; Moore, Linda; Hastings, Richard P.; Christian-Jones, Ceri
Background: The Behaviour Problems Inventory-Short Form (BPI-S) is a spin-off of the BPI-01 that was empirically developed from a large BPI-01 data set. In this study, the reliability and factorial validity of the BPI-S was investigated for the first time on newly collected data from adults with intellectual disabilities. Methods: The sample…
Patten, Anna R; Sawchuk, Scott; Wortman, Ryan C; Brocardo, Patricia S; Gil-Mohapel, Joana; Christie, Brian R
Prenatal ethanol exposure (PNEE) causes significant deficits in functional (i.e., synaptic) plasticity in the dentate gyrus (DG) and cornu ammonis (CA) hippocampal sub-regions of young adult male rats. Previous research has shown that in the DG, these deficits are not apparent in age-matched PNEE females. This study aimed to expand these findings and determine if PNEE induces deficits in hippocampal-dependent behaviours in both male and female young adult rats (PND 60). The metric change behavioural test examines DG-dependent deficits by determining whether an animal can detect a metric change between two identical objects. The temporal order behavioural test is thought to rely in part on the CA sub-region of the hippocampus and determines whether an animal will spend more time exploring an object that it has not seen for a larger temporal window as compared to an object that it has seen more recently. Using the liquid diet model of FASD (where 6.6% (v/v) ethanol is provided through a liquid diet consumed ad libitum throughout the entire gestation), we found that PNEE causes a significant impairment in the temporal order task, while no deficits in the DG-dependent metric change task were observed. There were no significant differences between males and females for either task. These results indicate that behaviours relying partially on the CA-region may be more affected by PNEE than those that rely on the DG.
Dent, Claire L; Isles, Anthony R
Imprinted genes are defined by their parent-of-origin-specific monoallelic expression. Although the epigenetic mechanisms regulating imprinted gene expression have been widely studied, their functional importance is still unclear. Imprinted genes are associated with a number of physiologies, including placental function and foetal growth, energy homeostasis, and brain and behaviour. This review focuses on genomic imprinting in the brain and on two imprinted genes in particular, Nesp and paternal Grb10, which, when manipulated in animals, have been shown to influence adult behaviour. These two genes are of particular interest as they are expressed in discrete and overlapping neural regions, recognised as key "imprinting hot spots" in the brain. Furthermore, these two genes do not appear to influence placental function and/or maternal provisioning of offspring. Consequently, by understanding their behavioural function we may begin to shed light on the evolutionary significance of imprinted genes in the adult brain, independent of the recognised role in maternal care. In addition, we discuss the potential future directions of research investigating the function of these two genes and the behavioural role of imprinted genes more generally.
Pich, Jacqueline; Hazelton, Michael; Kable, Ashley
Violence in healthcare is a significant issue and one that is increasing in prevalence globally. Nurses have been identified as the professional group at most risk, with patients the main source of this violence. The aim of this study was to describe the experiences of Australian ED nurses with episodes of patient-related violence from young adults (16-25years of age) and the parents of paediatric patients. Data analysis of semi-structured interviews led to the identification of antecedents to episodes of violence and behaviours specific to these two groups of interest. These behaviours included: "performing" and attention-seeking behaviours and violent behaviours including both verbal and physical abuse. Antecedents discussed by participants included: parental emotions and alcohol and substance abuse. Overall the results speak to a working environment where participants regularly feel unsafe. Violence in the ED is perceived to occur frequently and to such an extent that participants have become resigned to expect and accept it as part of their job. The role played by distinct groups such as young adults and the parents of paediatric patients must be acknowledged and this knowledge used along with other known risk factors to help identify patients at risk of potential violence.
In four experiments with 4-, 6-, and 9-year-old children and adults, the hypothesis was tested that, all other conditions being equal, a novel and unusual event elicits stronger curiosity and exploratory behaviour if its suggested explanation involves an element of the supernatural than if it does not (the impossible over possible effect - the I/P effect). Participants were shown an unusual phenomenon (a spontaneous disintegration of a physical object in an apparently empty box) framed in the context of either a magical (the impossible event) or scientific (the possible event) explanation. In the verbal trial, participants showed a clear understanding of the difference between the effect of genuine magic and the effect of a trick. In the behavioural trial, both children and adults showed the I/P effect. They were more likely to run the risk of losing their valuable objects in order to explore the impossible event than the possible event. Follow-up experiments showed that the I/P effect couldn't be explained as an artifact of the different degrees of cost of exploratory behaviour in the possible and impossible conditions or as a result of misinterpreting magic as tricks. The I/P effect emerged when the cost of exploratory behaviour was moderate and disappeared when the cost was perceived as too high or too low.
Menozzi, Davide; Sogari, Giovanni; Mora, Cristina
Although fruit and vegetable consumption is highly recommended for a healthy and balanced daily diet, several European countries do not meet these recommendations. In Italy, only 45% of young people are consuming at least one portion of vegetables per day. Therefore, this paper aims to understand the main determinants of vegetables consumption among young adults to suggest possible intervention strategies. A cross-sectional study was conducted on a samples of Italian students (n = 751), using the theory of planned behaviour (TPB) as a conceptual framework. A structural equation model (SEM) was developed to test the TPB predictors for vegetable consumption, and the role of background factors (socio-demographic and personal characteristics) in improving the TPB model's explaining power. Overall, 81% and 68%, respectively, of intentions and behaviour variance is explained by the TPB model. Socio-demographic and personal characteristics were found to influence intentions and behaviour indirectly by their effects on the theory's more proximal determinants. Interventions should be targeted to improve perceived behavioural control (PBC), attitudes and subjective norms that significantly affect intentions. Tailored interventions for male students, enrolled in courses other than food science, and doing less physical activity may have a larger effect on behavioural change.
Díaz-Fleischer, Francisco; Arredondo, José; Aluja, Martín
Early adult experiences in enriched environments favours animal brain and behavioural development ultimately resulting in an increased fitness. However, measuring the effect of environmental enrichment in animal behaviour in nature is often a complicated task, considering the complexity of the natural environment. We expanded previous studies to evaluate how early experience in an enriched environment affects copulation behaviour when animals are confronted with a complex semi-natural environment. Anastrepha ludens flies are an ideal model system for studying these effects because their natural habitats differ significantly from the cage environments in which these flies are reared for biological control purposes. For example, in the field, males form leks of up to six individuals. Each male defends a territory represented by a tree leaf whereas in rearing cages, territories are completely reduced because of the high population density. In a series of three experiments, we observed that male density represented the most influential stimulus for A. ludens male copulation success. Males that experienced lower densities in early adulthood obtained the highest proportion of copulations. By contrast, female copulation behaviour was not altered by female density. However, exposure to natural or artificial leaves in cages in which flies were kept until tested influenced female copulation behaviour. Females that were exposed to enriched environments exhibited a shorter latency to mate and shorter copulation durations with males than females reared in poor environments. We discuss the influence of early experience on male copulation success and female-mating choosiness.
Russell, Simon J; Hughes, Karen; Bellis, Mark A
Objectives To examine the relative contribution of childhood experience, measured by childhood violence and childhood happiness, and adult well-being on adult eating preferences and behaviours, independent of proximal factors such as current deprivation. Design A cross-sectional, stratified, randomised sample survey using retrospective measures of childhood violence and happiness and self-reported measures of current well-being. Setting The North West Region of England between September 2012 and March 2013. Participants Individuals aged 18–95-year-olds from randomly selected households (participation was successful for 90% of eligible households and 78% of the total visited addresses; n=11 243). Outcomes Dichotomised measures for preference of healthy foods or ‘feel good’ foods and low or high daily fruit and vegetable consumption. Results After correcting for demographics, combined categories for childhood experience and dichotomised measures of adult well-being were found to be significantly related to adult food preferences and eating behaviours. Participants with unhappy and violent childhoods compared to those with happy and non-violent childhoods had adjusted ORs (95% CI, significance) of 2.67 (2.15 to 3.06, p<0.001) of having low daily fruit and vegetable intake (two or less portions) and 1.53 (1.29 to 1.81, p<0.001) of choosing ‘feel good’ foods over foods which were good for their long term health. Conclusions Daily intake of fruit and vegetables, linked to non-communicable diseases, and preference for ‘feel good’ foods, linked to obesity, are affected by childhood experience and adult well-being independent of demographic factors. Preventative interventions which support parent–child relationships and improve childhood experience are likely to reduce the development of poor dietary and other health-risk behaviours. PMID:26743696
Huxley, Adam; Van-Schaik, Paul; Witts, Paul
This study investigated the frequency and severity of challenging behaviour in adults with Down's syndrome with and without signs of dementia. Care staff were interviewed using the Aberrant Behaviour Checklist-Community version (M.G. Aman & N.N. Singh, Slosson, East Aurora, NY, 1994), to investigate the frequency and severity of challenging…
Saage, Andrea; Vadstein, Olav; Sommer, Ulrich
The feeding behaviour of adults of the marine calanoid copepod Centropages hamatus was studied in laboratory experiments with ciliates and phytoplankton as food sources. The ingestion rate of algal (flagellates, diatoms) and ciliate prey (oligotrichs) as a function of prey concentration could be described by a Holling type III functional response, with close to zero ingestion rates at concentrations below 5 µg C l - 1 . In general, ingestion of ciliates was higher than ingestion of algae, and maximum feeding rates by adult males reached were half the feeding rates of adult females at prey concentrations exceeding 50 µg C l - 1 . When diatoms and ciliates were offered together C. hamatus (both sexes) fed exclusively on ciliates as long as they contributed with more than 5% to the mixture. This indicates the capability of active prey selection and switching between suspension feeding and ambush predation. Therefore, the feeding behaviour of adult C. hamatus can be characterised as omnivorous with a preference for larger motile prey. This implies a trophic level above two, if there is a sufficient abundance of protozoan food available.
Poppes, P; van der Putten, A A J; ten Brug, A; Vlaskamp, C
A study has shown that staff do not generally perceive challenging behaviour in people with profound intellectual and multiple disabilities (PIMD) as being of serious consequence. In this study we aimed to gain a better understanding of the causal explanations that direct care and support staff give for challenging behaviour in this group. The purpose of this study was twofold: (1) to determine the way staff attribute challenging behaviour in children and adults with PIMD; and (2) to analyse whether more experienced staff attribute challenging behaviour in children and adults with PIMD differently than less experienced staff. In total, 195 direct support staff and an equal number of children and adults with PIMD participated in the study. Direct support staff filled out the Challenging behaviour Attribution Scale (five causal explanatory models of challenging behaviour) to explain challenging behaviour in one individual that they supported. The results show that direct support staff as a whole report the biomedical model as the most plausible explanation for challenging behaviour in children and adults with PIMD. However, in the present study the mean scores on all models are low. This might indicate that a large number of staff found none of the models particularly useful as possible explanations of challenging behaviour in people with PIMD. This could mean that staff have difficulties stating the cause of challenging behaviour in this group. Another possible explanation could be that there is little scientific knowledge about causing and maintaining factors of challenging behaviour in people with PIMD. It could also mean that staff have additional explanations for challenging behaviour in this target group that are not mentioned in the instrument used. Future research should address these issues. No differences were found between more experienced and less experienced direct support staff.
Smidt, Andy; Balandin, Susan; Reed, Vicki; Sigafoos, Jeff
Background: Challenging behaviour often serves a communicative function. It therefore stands to reason that the residential staff working in developmental disability services require training to foster appropriate communicative interactions with adults with challenging behaviour. Method: Eighteen members of staff working in three residential…
Baker, J. K.; Seltzer, M. M.; Greenberg, J. S.
Background: Studies have linked the behaviour problems of children with fragile X syndrome (FXS) to maternal well-being, but less is known about how behaviour problems relate to important family factors such as marital satisfaction and family cohesion. Methods: Married mothers of 115 adolescents and adults with FXS completed questionnaires and…
Chin, Luzy Siu-Hei; Chan, Joanne Chung-Yan
Objectives: This is an exploratory study to examine the relations among self-esteem, oral health behaviours and clinical oral health status in Chinese adults. In addition, gender differences in clinical oral health status and oral health behaviours were explored. Methods: Participants were 192 patients from a private dental clinic in Hong Kong…
Gonzalez-Castañeda, Rocio E.; Galvez-Contreras, Alma Y.; Martínez-QUEZADA, Carlos J.; Jauregui-Huerta, Fernando; Grcia-Estrada, Joaquin; Ramos-Zuñiga; Luquin; Gonzalez-Perez
Anxiety and depressive symptoms are generated after paradoxical sleep deprivation (PSD). However, it is not clear whether PSD produces differential effects between females and males. The aim of this study was to assess the effect of PSD on anxiety- and depressive-like behaviors between sexes. Male and female BALB/c mice were divided in three groups: the control group, the 48-h PSD group and the 96-h PSD group. Immediately after PSD protocols, the forced swimming and open field test were applied. Sucrose consumption test was used to evaluate the middle-term effect of PSD. We found that corticosterone serum levels showed significant differences in the 96-h PSD females as compared to 96-h PSD males. In the open-field test, the 48-h and 96-h PSD females spent more time at the periphery of the field, and showed high locomotion as compared to males. In the elevated plus maze, the 48-h PSD females spent more time in closed arms than males, which is compatible with anxiety-like behavior. The forced swim test indicated that the 96-h PSD males spent more time swimming as compared to the 96-h PSD females. Remarkably, the 96-h PSD males had lower sucrose intake than the 96-h PSD females, which suggest that male mice have proclivity to develop a persistent depressive-like behavior late after PSD. In conclusion, male mice showed a significant trend to depressive-like behaviors late after sleep deprivation. Conversely, female have a strong tendency to display anxiety- and depressive-like behaviors immediately after sleep deprivation. PMID:26548630
Davies, Bronwen; Frude, Neil; Jenkins, Rosemary; Harding, Cathy; Hill, Caley
This preliminary study explores the relationships between challenging behaviour and emotional perception in a population of adults with intellectual disabilities, in order to establish whether there are grounds for further study. Cross-sectional data were collected from 96 participants with intellectual disabilities and 95 carers. The service user participants completed the Emotional Perception Questionnaire, whilst carers completed the Checklist for Challenging Behaviour. Correlational analyses were employed to analyse relationships between the variables. A post hoc between-group analysis was conducted to compare the emotional recognition abilities of people with high-frequency challenging behaviour with those with low-frequency challenging behaviour. Significant negative associations were found between emotional perception and challenging behaviour frequency and management difficulty. Significant differences in emotional perception abilities were found between people with high frequency and those with low-frequency challenging behaviours. The study suggests that emotional perception is important in understanding challenging behaviour.
Sambisa, William; Curtis, Sian L; Stokes, C Shannon
Understanding the social and cultural contextual determinants of sexual behaviour of adolescents and young adults is an essential step towards curtailing the spread of HIV. This study examined the effects of one cultural factor, ethnicity, on sexual abstinence, faithfulness, condom use at last sex, and risky sex among young people in Zimbabwe. Data from the cross-sectional, population-based 2005-06 Zimbabwe Demographic and Health Survey were used. Net of the effect of sociodemographic and social-cognitive factors, and using multinomial logistic regression, ethnicity was found to have a strong and consistent effect on sexual behaviour among youth. In addition, the study found that there were ethnic-specific and within-gender differences in sexual behaviour, for both men and women. Shona youth were more likely to be abstinent than Ndebele youth. Compared with Shona youth, Ndebele youth were more likely to have engaged in risky sex. However, Ndebele men were more likely have used condoms at last sex, compared with Shona men. For both men and women, sexual behaviour was more socially controlled. School attendance and religion exerted protective effects on sexual abstinence. For men only, those living in rural areas were less likely to be faithful and more likely to have engaged in risky sexual behaviour than those living in urban areas. The study attests to the fact that ethnic norms and ideologies of sexuality need to be identified and more thoroughly understood. In addition, the study provides evidence that in order to promote safe and healthy sexuality among young people in Zimbabwe, cultural, social and gender-specific approaches to the development of HIV prevention strategies should be seriously considered. Current success in the Abstinence, Being faithful and Condom use (ABC) approach could be strengthened by recognizing and responding to cultural forces that reproduce and perpetuate risky sexual behaviours.
Mengoni Goñalons, Carolina; Farina, Walter Marcelo
Imidacloprid (IMI), a neonicotinoid used for its high selective toxicity to insects, is one of the most commonly used pesticides. However, its effect on beneficial insects such as the honeybee Apis mellifera L is still controversial. As young adult workers perform in-hive duties that are crucial for colony maintenance and survival, we aimed to assess the effect of sublethal IMI doses on honeybee behaviour during this period. Also, because this insecticide acts as a cholinergic-nicotinic agonist and these pathways take part in insect learning and memory processes; we used IMI to assess their role and the changes they suffer along early adulthood. We focused on appetitive behaviours based on the proboscis extension response. Laboratory reared adults of 2 to 10 days of age were exposed to sublethal IMI doses (0.25 or 0.50ng) administered orally or topically prior to behavioural assessment. Modification of gustatory responsiveness and impairment of learning and memory were found as a result of IMI exposure. These outcomes differed depending on age of evaluation, type of exposure and IMI dose, being the youngest bees more sensitive and the highest oral dose more toxic. Altogether, these results imply that IMI administered at levels found in agroecosystems can reduce sensitivity to reward and impair associative learning in young honeybees. Therefore, once a nectar inflow with IMI traces is distributed within the hive, it could impair in-door duties with negative consequences on colony performance. PMID:26488410
Mengoni Goñalons, Carolina; Farina, Walter Marcelo
Imidacloprid (IMI), a neonicotinoid used for its high selective toxicity to insects, is one of the most commonly used pesticides. However, its effect on beneficial insects such as the honeybee Apis mellifera L is still controversial. As young adult workers perform in-hive duties that are crucial for colony maintenance and survival, we aimed to assess the effect of sublethal IMI doses on honeybee behaviour during this period. Also, because this insecticide acts as a cholinergic-nicotinic agonist and these pathways take part in insect learning and memory processes; we used IMI to assess their role and the changes they suffer along early adulthood. We focused on appetitive behaviours based on the proboscis extension response. Laboratory reared adults of 2 to 10 days of age were exposed to sublethal IMI doses (0.25 or 0.50ng) administered orally or topically prior to behavioural assessment. Modification of gustatory responsiveness and impairment of learning and memory were found as a result of IMI exposure. These outcomes differed depending on age of evaluation, type of exposure and IMI dose, being the youngest bees more sensitive and the highest oral dose more toxic. Altogether, these results imply that IMI administered at levels found in agroecosystems can reduce sensitivity to reward and impair associative learning in young honeybees. Therefore, once a nectar inflow with IMI traces is distributed within the hive, it could impair in-door duties with negative consequences on colony performance.
Voyer, Philippe; Verreault, René; Azizah, Ginette M; Desrosiers, Johanne; Champoux, Nathalie; Bédard, Annick
Background Verbal and physical aggressive behaviours are among the most disturbing and distressing behaviours displayed by older patients in long-term care facilities. Aggressive behaviour (AB) is often the reason for using physical or chemical restraints with nursing home residents and is a major concern for caregivers. AB is associated with increased health care costs due to staff turnover and absenteeism. Methods The goals of this secondary analysis of a cross-sectional study are to determine the prevalence of verbal and physical aggressive behaviours and to identify associated factors among older adults in long-term care facilities in the Quebec City area (n = 2 332). Results The same percentage of older adults displayed physical aggressive behaviour (21.2%) or verbal aggressive behaviour (21.5%), whereas 11.2% displayed both types of aggressive behaviour. Factors associated with aggressive behaviour (both verbal and physical) were male gender, neuroleptic drug use, mild and severe cognitive impairment, insomnia, psychological distress, and physical restraints. Factors associated with physical aggressive behaviour were older age, male gender, neuroleptic drug use, mild or severe cognitive impairment, insomnia and psychological distress. Finally, factors associated with verbal aggressive behaviour were benzodiazepine and neuroleptic drug use, functional dependency, mild or severe cognitive impairment and insomnia. Conclusion Cognitive impairment severity is the most significant predisposing factor for aggressive behaviour among older adults in long-term care facilities in the Quebec City area. Physical and chemical restraints were also significantly associated with AB. Based on these results, we suggest that caregivers should provide care to older adults with AB using approaches such as the progressively lowered stress threshold model and reactance theory which stress the importance of paying attention to the severity of cognitive impairment and avoiding the use
Day, Ashley K; Wilson, Carlene J; Hutchinson, Amanda D; Roberts, Rachel M
Australia has a significant proportion of residents of Asian heritage. Although the incidence of skin cancer is lower in those of Asian heritage than Caucasians, their prognosis is often worse. Sociocultural variables are central to the tanning behaviours of individuals from Western cultures. We examined the role of sociocultural variables in the tanning behaviours (outdoor tanning, indoor/solarium and fake tan use) among Asian Australians. A sample of 399 young adults identifying either as a person of Asian heritage or as Asian Australian participated in an online survey. Our results suggest that Asian Australians are at risk of skin cancer; over 35 % of the sample reported engaging in outdoor tanning and over 10 % in solarium tanning. After controlling for demographic factors and skin cancer knowledge, preferring a darker skin tone and being acculturated to Australia were significantly associated with tanning behaviour. Participants' low levels of skin cancer knowledge are of concern, and possibilities for improving knowledge levels in this group are considered. Further, we recommended that future research studies investigate sociocultural and appearance-related beliefs associated with tanning behaviours in this population, in order to determine best avenues for intervention.
Vinish, Monika; Elnabawi, Ahmed; Milstein, Jean A; Burke, Jesse S; Kallevang, Jonathan K; Turek, Kevin C; Lansink, Carien S; Merchenthaler, Istvan; Bailey, Aileen M; Kolb, Bryan; Cheer, Joseph F; Frost, Douglas O
Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug (APD) treatment. Most APDs are potent antagonists or partial agonists of dopamine (DA) D₂ receptors; atypical APDs also have multiple serotonergic activities. DA and serotonin regulate many neurodevelopmental processes. Thus, early life APD treatment can, potentially, perturb these processes, causing long-term behavioural and neurobiological sequelae. We treated adolescent, male rats with olanzapine (Ola) on post-natal days 28-49, under dosing conditions that approximate those employed therapeutically in humans. As adults, they exhibited enhanced conditioned place preference for amphetamine, as compared to vehicle-treated rats. In the nucleus accumbens core, DA D₁ receptor binding was reduced, D₂ binding was increased and DA release evoked by electrical stimulation of the ventral tegmental area was reduced. Thus, adolescent Ola treatment enduringly alters a key behavioural response to rewarding stimuli and modifies DAergic neurotransmission in the nucleus accumbens. The persistence of these changes suggests that even limited periods of early life Ola treatment may induce enduring changes in other reward-related behaviours and in behavioural and neurobiological responses to therapeutic and illicit psychotropic drugs. These results underscore the importance of improved understanding of the enduring sequelae of paediatric APD treatment as a basis for weighing the benefits and risks of adolescent APD therapy, especially prophylactic treatment in high-risk, asymptomatic patients.
Wakabayashi, Chisato; Numakawa, Tadahiro; Odaka, Haruki; Ooshima, Yoshiko; Kiyama, Yuji; Manabe, Toshiya; Kunugi, Hiroshi; Iwakura, Yoichiro
Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus.
Ji, Mu-Huo; Jia, Min; Zhang, Ming-Qiang; Liu, Wen-Xue; Xie, Zhong-Cong; Wang, Zhong-Yun; Yang, Jian-Jun
Post-traumatic stress disorder (PTSD) is a psychiatric disease that has substantial health implications, including high rates of health morbidity and mortality, as well as increased health-related costs. Although many pharmacological agents have proven the effects on the development of PTSD, current pharmacotherapies typically only produce partial improvement of PTSD symptoms. Dexmedetomidine is a selective, short-acting α2-adrenoceptor agonist, which has anxiolytic, sedative, and analgesic effects. We therefore hypothesized that dexmedetomidine possesses the ability to prevent the development of PTSD and alleviate its symptoms. By using the rat model of PTSD induced by five electric foot shocks followed by three weekly exposures to situational reminders, we showed that the stressed rats displayed pronounced anxiety-like behaviors and cognitive impairments compared to the controls. Notably, repeated administration of 20μg/kg dexmedetomidine showed impaired fear conditioning memory, decreased anxiety-like behaviors, and improved spatial cognitive impairments compared to the vehicle-treated stressed rats. These data suggest that dexmedetomidine may exert preventive and protective effects against anxiety-like behaviors and cognitive impairments in the rats with PTSD after repeated administration.
Zhao, Liping; Kim, Ki Woo; Ikeda, Yayoi; Anderson, Kimberly K.; Beck, Laurel; Chase, Stephanie; Tobet, Stuart A.; Parker, Keith L.
Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor. PMID:18372344
Tapia-Osorio, Araceli; Salgado-Delgado, Roberto; Angeles-Castellanos, Manuel; Escobar, Carolina
Depression is strongly associated with the circadian system, disruption of the circadian system leads to increased propensity to disease and to mood disorders including depression. The present study explored in rats the effects of circadian disruption by constant light on behavioral and hormonal indicators of a depressive-like condition and on the biological clock, the suprachiasmatic nucleus (SCN). Exposure to constant light for 8 weeks resulted in loss of circadian patterns of spontaneous general activity, melatonin and corticosterone. Moreover these rats exhibited anhedonia in a sucrose consumption test, and increased grooming in the open-field test, which reflects an anxiety-like condition. In the SCN decreased cellular activation was observed by c-Fos immunohistochemistry. In rats exposed to constant darkness, circadian behavioral and hormonal patterns remained conserved, however mild depressive-like indicators were observed in the anhedonia test and mild anxiety-like behaviors were observed in the open field test. Data indicate that chronic conditions of LL or DD are both disruptive for the activity of the SCN leading to depression- and anxiety-like behavior. Present results point out the main role played by the biological clock and the risk of altered photoperiods on affective behavior.
Zhao, Liping; Kim, Ki Woo; Ikeda, Yayoi; Anderson, Kimberly K; Beck, Laurel; Chase, Stephanie; Tobet, Stuart A; Parker, Keith L
Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor.
Ahmad, Muhammad; Chaudhary, Safee Ullah; Afzal, Ahmed Jawaad; Tariq, Muhammad
Drosophila melanogaster larvae are classified as herbivores and known to feed on non-carnivorous diet under normal conditions. However, when nutritionally challenged these larvae exhibit cannibalistic behaviour by consuming a diet composed of larger conspecifics. Herein, we report that cannibalism in Drosophila larvae is confined not only to scavenging on conspecifics that are larger in size, but also on their eggs. Moreover, such cannibalistic larvae develop as normally as those grown on standard cornmeal medium. When stressed, Drosophila melanogaster larvae can also consume a carnivorous diet derived from carcasses of organisms belonging to diverse taxonomic groups, including Musca domestica, Apis mellifera, and Lycosidae sp. While adults are ill-equipped to devour conspecific carcasses, they selectively oviposit on them and also consume damaged cadavers of conspecifics. Thus, our results suggest that nutritionally stressed Drosophila show distinct as well as unusual feeding behaviours that can be classified as detritivorous, cannibalistic and/or carnivorous. PMID:26399327
Prasher, V.; Farooq, A.; Holder, R.
The diagnosis of dementia in Alzheimer's disease remains at times problematic in adults with intellectual disability. The analysis of 5-year consecutive data developed a researched-based clinical screening tool for dementia in Alzheimer's disease in adults with Down syndrome. The Adaptive Behaviour Dementia Questionnaire (ABDQ) is a 15-item…
Shephard, E; Jackson, G M; Groom, M J
This study examined neurocognitive differences between children and adults in the ability to learn and adapt simple stimulus-response associations through feedback. Fourteen typically developing children (mean age=10.2) and 15 healthy adults (mean age=25.5) completed a simple task in which they learned to associate visually presented stimuli with manual responses based on performance feedback (acquisition phase), and then reversed and re-learned those associations following an unexpected change in reinforcement contingencies (reversal phase). Electrophysiological activity was recorded throughout task performance. We found no group differences in learning-related changes in performance (reaction time, accuracy) or in the amplitude of event-related potentials (ERPs) associated with stimulus processing (P3 ERP) or feedback processing (feedback-related negativity; FRN) during the acquisition phase. However, children's performance was significantly more disrupted by the reversal than adults and FRN amplitudes were significantly modulated by the reversal phase in children but not adults. These findings indicate that children have specific difficulties with reinforcement learning when acquired behaviours must be altered. This may be caused by the added demands on immature executive functioning, specifically response monitoring, created by the requirement to reverse the associations, or a developmental difference in the way in which children and adults approach reinforcement learning.
Mesas, A E; León-Muñoz, L M; Guallar-Castillón, P; Graciani, A; Gutiérrez-Fisac, J L; López-García, E; Aguilera, M T; Banegas, J R; Rodríguez-Artalejo, F
Knowledge of the socio-demographic distribution of eating behaviours can aid our understanding of their contribution to the obesity epidemic and help to address healthy eating interventions to those who can benefit most. This cross-sectional study assessed the frequency of self-reported eating behaviours among 11,603 individuals representative of the non-institutionalized Spanish population aged ≥ 18 years in the period 2008-2010. In the adult population of Spain, 24.3% had lunch and 18.2% had dinner away from home >3 times per month. About three-fourths of adults did not plan the amount of food to be eaten, and did not choose light foods and/or skim dairy products. Also, 26% did not trim visible fat from meat, and 74.7% usually ate while watching television. Compared with individuals with primary or less education, those with university studies were more likely to remove fat from meat (age- and sex-adjusted odds ratio [aOR] 1.25; 95% confidence interval [CI] 1.08-1.44), and to choose light food and/or skim dairy (aOR 1.50; 95% CI 1.30-1.77), and less likely to eat while watching television (aOR 0.54; 95% CI 0.47-0.63). In conclusion, the prevalence of several obesity-related eating behaviours is high in Spain, which indicates a deficient implementation of dietary guidelines. Socioeconomic inequalities in eating behaviours should also be addressed.
Moise, Anna M.; Eisenstein, Sarah A.; Astarita, Giuseppe; Piomelli, Daniele; Hohmann, Andrea G.
Rationale An endocannabinoid signaling system has not been identified in hamsters. Objective We examined the existence of an endocannabinioid signaling system in Syrian hamsters using neuroanatomical, biochemical and behavioral pharmacological approaches. Method The distribution of cannabinoid receptors was mapped and membrane fatty-acid amide hydrolase (FAAH) activity and levels of fatty-acid amides were measured in hamster brain. The impact of cannabinoid CB1 receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test and models of unconditioned and conditioned social defeat. Results A characteristic heterogeneous distribution of cannabinoid receptors was detected in hamster brain using [3H]CP55,940 binding and autoradiography. The FAAH inhibitor URB597 inhibited FAAH activity (IC50 = 12.8 nM) and elevated levels of fatty-acid amides (N-palmitoyl ethanolamine (PEA) and N-oleoyl ethanolamine (OEA)) in hamster brain. Anandamide levels were not reliably altered. The cannabinoid agonist WIN55,212-2 (1– 10 mg/kg i.p.) induced CB1-mediated motor ataxia. Blockade of CB1 with rimonabant (5 mg/kg i.p.) induced anxiogenic-like behavior in the elevated plus maze. URB597 (0.1–0.3 mg/kg i.p.) induced CB1-mediated anxiolytic-like effects in elevated plus maze, similar to the benzodiazepine diazepam (2 mg/kg i.p.). Diazepam (2–6 mg/kg i.p.) suppressed the expression, but not the acquisition, of conditioned defeat. By contrast, neither URB597 (0.3–3.0 mg/kg i.p.) nor rimonabant (5 mg/kg i.p.) altered unconditioned or conditioned social defeat or rota-rod performance. Conclusions Endocannabinoids engage functional CB1 receptors in hamster brain to suppress anxiety-like behavior and undergo enzymatic hydrolysis catalyzed by FAAH. Our results further suggest that neither unconditioned nor conditioned social defeat in the Syrian hamster is dependent upon cannabinoid CB1 receptor activation. PMID:18545985
Kumari, Anita; Singh, Padmanabh; Baghel, Meghraj Singh; Thakur, M K
Adverse early life experience is prominent risk factors for numerous psychiatric illnesses, including mood and anxiety disorders. It imposes serious long-term costs on the individual as well as health and social systems. Hence, developing therapies that prevent the long-term consequences of early life stress is of utmost importance, and necessitates a better understanding of the mechanisms by which early life stress triggers long-lasting alterations in gene expression and behavior. Post-weaning isolation rearing of rodents models the behavioral consequences of adverse early life experiences in humans and it is reported to cause anxiety like behavior which is more common in case of females. Therefore, in the present study, we have studied the impact of social isolation of young female mice for 8weeks on the anxiety like behavior and the underlying molecular mechanism. Elevated plus maze and open field test revealed that social isolation caused anxiety like behavior. BDNF, a well-known molecule implicated in the anxiety like behavior, was up-regulated both at the message and protein level in cerebral cortex by social isolation. CREB-1 and CBP, which play a crucial role in BDNF transcription, were up-regulated at mRNA level in cerebral cortex by social isolation. HDAC-2, which negatively regulates BDNF expression, was down-regulated at mRNA and protein level in cerebral cortex by social isolation. Furthermore, BDNF acts in concert with Limk-1, miRNA-132 and miRNA-134 for the regulation of structural and morphological plasticity. Social isolation resulted in up-regulation of Limk-1 mRNA and miRNA-132 expression in the cerebral cortex. MiRNA-134, which inhibits the translation of Limk-1, was decreased in cerebral cortex by social isolation. Taken together, our study suggests that social isolation mediated anxiety like behavior is associated with up-regulation of BDNF expression and concomitant increase in the expression of CBP, CREB-1, Limk-1 and miRNA-132, and decrease
Paris, Jason J.; Fenwick, Jason; McLaughlin, Jay P.
Increased anxiety is co-morbid with human immunodeficiency virus (HIV) infection. Actions of the neurotoxic HIV-1 regulatory protein, Tat, may contribute to affective dysfunction. We hypothesized that Tat expression would increase anxiety-like behavior of female GT-tg bigenic mice that express HIV-1 Tat protein in the brain in a doxycycline-dependent manner. Furthermore, given reports that HIV-induced anxiety may occur at lower rates among women, and that the neurotoxic effects of Tat are ameliorated by sex steroids in vitro, we hypothesized that 17β-estradiol and/or progesterone would ameliorate Tat-induced anxiety-like effects. Among naturally-cycling proestrous and diestrous mice, Tat-induction via 7 days of doxycycline treatment significantly increased anxiety-like responding in an open field, elevated plus maze and a marble-burying task, compared to treatment with saline. Proestrous mice demonstrated less anxiety-like behavior than diestrous mice in the open field and elevated plus maze, but these effects did not significantly interact with Tat-induction. Among ovariectomized mice, doxycycline-induced Tat protein significantly increased anxiety-like behavior in an elevated plus maze and a marble burying task compared to saline-treated mice, but not an open field (where anxiety-like responding was already maximal). Co-administration of progesterone (4 mg/kg), but not 17β-estradiol (0.09 mg/kg), with doxycycline significantly ameliorated anxiety-like responding in the elevated plus maze and marble burying tasks. When administered together, 17β-estradiol partially antagonized the protective effects of progesterone on Tat-induced anxiety-like behavior. These findings support evidence of steroid-protection over HIV-1 proteins, and extend them by demonstrating the protective capacity of progesterone on Tat-induced anxiety-like behavior of ovariectomized female mice. PMID:24726788
Chen, E Y; Leonard, J B K; Ueda, H
Adult chum salmon Oncorhynchus keta homing behaviour in a two-choice test tank (Y-maze) was monitored using a passive integrated transponder (PIT)-tag system in response to river-specific dissolved free amino-acid (DFAA) profiles and revealed that the majority of O. keta showed a preference for artificial natal-stream water and tended to stay in this maze arm for a longer period; natal-stream water was chosen over a nearby tributary's water, but not when the O. keta were presented with a non-tributary water. The results demonstrate the ability of O. keta to discriminate artificial stream waters containing natural levels of DFAA.
Handa, R J; Ogawa, S; Wang, J M; Herbison, A E
Oestradiol exerts a profound influence upon multiple brain circuits. For the most part, these effects are mediated by oestrogen receptor (ER)α. We review here the roles of ERβ, the other ER isoform, in mediating rodent oestradiol-regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin secretion, and adult neurogenesis. Evidence exists for: (i) ERβ located in the paraventricular nucleus underpinning the suppressive influence of oestradiol on the stress axis and anxiety-like behaviour; (ii) ERβ expressed in gonadotrophin-releasing hormone neurones contributing to oestrogen negative-feedback control of gonadotrophin secretion; (iii) ERβ controlling the offset of lordosis behaviour; (iv) ERβ suppressing aggressive behaviour in males; (v) ERβ modulating responses to social stimuli; and (vi) ERβ in controlling adult neurogenesis. This review highlights two major themes; first, ERβ and ERα are usually tightly inter-related in the oestradiol-dependent control of a particular brain function. For example, even though oestradiol feedback to control reproduction occurs principally through ERα-dependent mechanisms, modulatory roles for ERβ also exist. Second, the roles of ERα and ERβ within a particular neural network may be synergistic or antagonistic. Examples of the latter include the role of ERα to enhance, and ERβ to suppress, anxiety-like and aggressive behaviours. Splice variants such as ERβ2, acting as dominant negative receptors, are of further particular interest because their expression levels may reflect preceeding oestradiol exposure of relevance to oestradiol replacement therapy. Together, this review highlights the predominant modulatory, but nonetheless important, roles of ERβ in mediating the many effects of oestradiol upon adult brain function.
Keller, Kristin; Rodríguez López, Santiago; Carmenate Moreno, M Margarita; Acevedo Cantero, Paula
The aim of the present study is to explore the contribution of different types of meal intake behaviour on a healthy diet and seeks to find associations with food consumption habits. A cross-sectional survey with data from 1332 Spanish adults aged between 20 and 79 years was conducted. The survey was carried out during the cardiovascular health event 'Semanas del Corazon 2008' in four Spanish cities. Several food consumption habits such as the recommended intake of fruits, vegetables, milk and dairy products, as well as the regular consumption of fatty and salty food and ready-made meals, were used as dependent variables in logistic regression. We evaluated different meal intake behaviour such as the type of meals, snacking, and drinks taken with a meal. Our survey revealed that snacking is positively associated with the regular consumption of salty and fatty food, and having sugary drinks with meals was positively associated with the regular consumption of ready-made meals. Having a forenoon meal is positively associated with the consumption of two or more portions of milk and dairy products and vegetables, and taking an afternoon meal with the recommended intake of milk and dairy products and fruits. Drinking water during a meal increases the probability of consuming two or more portions of fruits and vegetables. Our results enhance the understanding of the contribution that meal intake behaviour makes to a healthy diet based on food consumption habits. This work provides an insight into eating behaviour and would make a useful contribution to interventions aimed at promoting healthier eating habits.
Lakerveld, J; Mackenbach, J D; Horvath, E; Rutters, F; Compernolle, S; Bárdos, H; De Bourdeaudhuij, I; Charreire, H; Rutter, H; Oppert, J-M; McKee, M; Brug, J
Too much sitting, and both short and long sleep duration are associated with obesity, but little is known on the nature of the relations between these behaviours. We therefore examined the associations between sleep duration and time spent sitting in adults across five urban regions in Europe. We used cross-sectional survey data from 6,037 adults (mean age 51.9 years (SD 16.4), 44.0% men) to assess the association between self-reported short (<6 h per night), normal (6-8 h per night) and long (>8 h per night) sleep duration with self-report total time spent sitting, time spent sitting at work, during transport, during leisure and while watching screens. The multivariable multilevel linear regression models were tested for moderation by urban region, age, gender, education and weight status. Because short sleepers have more awake time to be sedentary, we also used the percentage of awake time spent sedentary as an outcome. Short sleepers had 26.5 min day(-1) more sedentary screen time, compared with normal sleepers (CI 5.2; 47.8). No statistically significant associations were found with total or other domains of sedentary behaviour, and there was no evidence for effect modification. Long sleepers spent 3.2% higher proportion of their awake time sedentary compared with normal sleepers. Shorter sleep was associated with increased screen time in a sample of European adults, irrespective of urban region, gender, age, educational level and weight status. Experimental studies are needed to assess the prospective relation between sedentary (screen) time and sleep duration.
Hellemans, Kim G. C.; Verma, Pamela; Yoon, Esther; Yu, Wayne K.; Young, Allan H.; Weinberg, Joanne
Background Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neuro behavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic-pituitary-adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre-existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive- and anxiety-like behaviors in PAE animals. Methods Male and female offspring from prenatal alcohol (PAE), pair-fed (PF), and ad libitumfed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well-validated tasks sensitive to differences in depressive- and / or anxiety-like behaviors. Results We report here that the combination of PAE and CMS in adulthood increases depressive- and anxiety-like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of “behavioral despair” in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. Conclusions These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations. PMID:20102562
Huang, Max P; Radadia, Kushan; Macone, Brian W; Auerbach, Sanford H; Datta, Subimal
At present, eszopiclone and zolpidem are the most commonly prescribed drugs for treating insomnia. Despite the established relationship between sleep disturbance and anxiety, it remains unknown whether targeted treatment for insomnia may affect acute anxiety. Therefore, the objective of this study was to examine the effects of three different doses (1, 3, and 10mg/kg) of eszopiclone and zolpidem on the states of sleep and wakefulness, levels of anxiety-like behavior, and long-term contextual memory in footshock-induced anxious rats. The results of this study demonstrated that the administration of eszopiclone and zolpidem both were equally effective in attenuating footshock stressor-induced suppression of slow-wave sleep (SWS). The administration of eszopiclone at 1mg/kg or zolpidem at 1 and 3mg/kg doses showed a tendency for attenuating stressor-induced suppression of REM sleep. However, the REM sleep attenuating effects of these drugs disappeared when they were administered at higher doses. The administration of eszopiclone at 3 and 10mg/kg doses and zolpidem at all three doses reduced the power of electroencephalographic theta band frequencies during wakefulness. In addition, the administration of eszopiclone at 1 and 3mg/kg doses suppressed stressor-induced anxiety-like behavior. The administration of zolpidem at 1, 3, or 10mg/kg doses was not effective in attenuating stressor-induced anxiety-like behavior. Contextual memory after administration of eszopiclone at 1mg/kg dose had no effects, but was reduced significantly with increased dosage. Contextual memory after administration of zolpidem, at all three doses, was severely disrupted. The results of this study suggest that eszopiclone at a low dose could be used effectively to control anxiety and anxiety-induced insomnia.
Huang, Max P.; Radadia, Kushan; Macone, Brian W.; Auerbach, Sanford H.; Datta, Subimal
At present, eszopiclone and zolpidem are the most commonly prescribed drugs for treating insomnia. Despite the established relationship between sleep disturbance and anxiety, it remains unknown whether targeted treatment for insomnia may affect acute anxiety. Therefore, the objective of this study was to examine the effects of three different doses (1, 3, and 10 mg/kg) of eszopiclone and zolpidem on the states of sleep and wakefulness, levels of anxiety-like behavior, and long-term contextual memory in footshock-induced anxious rats. The results of this study demonstrated that the administration of eszopiclone and zolpidem both were equally effective in attenuating footshock stressor-induced suppression of slow-wave sleep (SWS). The administration of eszopiclone at 1 mg/kg or zolpidem at 1 and 3 mg/kg doses showed a tendency for attenuating stressor-induced suppression of REM sleep. However, the REM sleep attenuating effects of these drugs disappeared when they were administered at higher doses. The administration of eszopiclone at 3 and 10 mg/kg doses and zolpidem at all three doses reduced the power of electroencephalographic theta band frequencies during wakefulness. In addition, the administration of eszopiclone at 1 and 3 mg/kg doses suppressed stressor-induced anxiety-like behavior. The administration of zolpidem at 1, 3, or 10 mg/kg doses was not effective in attenuating stressor-induced anxiety-like behavior. Contextual memory after administration of eszopiclone at 1 mg/kg dose had no effects, but was reduced significantly with increased dosage. Contextual memory after administration of zolpidem, at all three doses, was severely disrupted. The results of this study suggest that eszopiclone at a low dose could be used effectively to control anxiety and anxiety-induced insomnia. PMID:20153782
Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G
Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the
Nakano, Tamami; Tanaka, Kyoko; Endo, Yuuki; Yamane, Yui; Yamamoto, Takahiro; Nakano, Yoshiaki; Ohta, Haruhisa; Kato, Nobumasa; Kitazawa, Shigeru
Eye tracking has been used to investigate gaze behaviours in individuals with autism spectrum disorder (ASD). However, traditional analysis has yet to find behavioural characteristics shared by both children and adults with ASD. To distinguish core ASD gaze behaviours from those that change with development, we examined temporo-spatial gaze patterns in children and adults with and without ASD while they viewed video clips. We summarized the gaze patterns of 104 participants using multidimensional scaling so that participants with similar gaze patterns would cluster together in a two-dimensional plane. Control participants clustered in the centre, reflecting a standard gaze behaviour, whereas participants with ASD were distributed around the periphery. Moreover, children and adults were separated on the plane, thereby showing a clear effect of development on gaze behaviours. Post hoc frame-by-frame analyses revealed the following findings: (i) both ASD groups shifted their gaze away from a speaker earlier than the control groups; (ii) both ASD groups showed a particular preference for letters; and (iii) typical infants preferred to watch the mouth rather than the eyes during speech, a preference that reversed with development. These results highlight the importance of taking the effect of development into account when addressing gaze behaviours characteristic of ASD.
Riemer, Stefanie; Müller, Corsin; Virányi, Zsófia; Huber, Ludwig; Range, Friederike
Studies on behavioural development in domestic dogs are of relevance for matching puppies with the right families, identifying predispositions for behavioural problems at an early stage, and predicting suitability for service dog work, police or military service. The literature is, however, inconsistent regarding the predictive value of tests performed during the socialisation period. Additionally, some practitioners use tests with neonates to complement later assessments for selecting puppies as working dogs, but these have not been validated. We here present longitudinal data on a cohort of Border collies, followed up from neonate age until adulthood. A neonate test was conducted with 99 Border collie puppies aged 2-10 days to assess activity, vocalisations when isolated and sucking force. At the age of 40-50 days, 134 puppies (including 93 tested as neonates) were tested in a puppy test at their breeders' homes. All dogs were adopted as pet dogs and 50 of them participated in a behavioural test at the age of 1.5 to 2 years with their owners. Linear mixed models found little correspondence between individuals' behaviour in the neonate, puppy and adult test. Exploratory activity was the only behaviour that was significantly correlated between the puppy and the adult test. We conclude that the predictive validity of early tests for predicting specific behavioural traits in adult pet dogs is limited.
Riemer, Stefanie; Müller, Corsin; Virányi, Zsófia; Huber, Ludwig; Range, Friederike
Studies on behavioural development in domestic dogs are of relevance for matching puppies with the right families, identifying predispositions for behavioural problems at an early stage, and predicting suitability for service dog work, police or military service. The literature is, however, inconsistent regarding the predictive value of tests performed during the socialisation period. Additionally, some practitioners use tests with neonates to complement later assessments for selecting puppies as working dogs, but these have not been validated. We here present longitudinal data on a cohort of Border collies, followed up from neonate age until adulthood. A neonate test was conducted with 99 Border collie puppies aged 2–10 days to assess activity, vocalisations when isolated and sucking force. At the age of 40–50 days, 134 puppies (including 93 tested as neonates) were tested in a puppy test at their breeders' homes. All dogs were adopted as pet dogs and 50 of them participated in a behavioural test at the age of 1.5 to 2 years with their owners. Linear mixed models found little correspondence between individuals' behaviour in the neonate, puppy and adult test. Exploratory activity was the only behaviour that was significantly correlated between the puppy and the adult test. We conclude that the predictive validity of early tests for predicting specific behavioural traits in adult pet dogs is limited. PMID:25003341
Weiss, Jonathan A; Lunsky, Yona
Individuals with Asperger syndrome are at increased risk for mental health problems compared with the general population, especially with regard to mood and anxiety disorders. Generic mental health services are often ill-equipped to offer psychotherapeutic treatments to this population, and specialized supports are difficult to find. This case series used a manualized cognitive behaviour therapy group programme (Mind Over Mood) with three adults diagnosed with Asperger syndrome, who were each unable to access psychotherapy through mainstream mental health services. This review highlights the benefits of a cognitive behaviour therapy (CBT) group approach for adults with Asperger syndrome and suggests some potential modifications to traditional CBT provision.
Nguyen, Linda; Bohlen, Joseph; Stricker, Janelle; Chahal, Ikttesh; Zhang, Hanting; Pistilli, Emidio E
A hippocampus-specific IL15RαKO mouse (hipIl15ra (fl/fl) /Cre(+)) was generated to test the hypothesis that the targeted deletion of interleukin-15 receptor alpha (IL-15Rα) in the hippocampus contributes to altered behavior, including greater levels of anxiety and ambulatory activity. Using Cre-loxP, exons 2 and 3 of the IL-15Rα gene were excised within the hippocampus, while normal expression was maintained within the rest of the brain. In the open field test (OFT), hipIl15ra (fl/fl) /Cre(+) spent a greater amount of time in the periphery and less time in the central portions of the chamber, and there was also a noticeable trend for decreased rearing activity; these behaviors are consistent with greater levels of anxiety-like behavior in these mice. However, there were no differences in the overall locomotor counts in the OFT when comparing hipIl15ra (fl/fl) /Cre(+) mice to their littermate controls. These data implicate IL-15-related signaling within the hippocampus has a role in anxiety-like behavior.
Matys, Tomasz; Pawlak, Robert; Matys, Elzbieta; Pavlides, Constantine; McEwen, Bruce S; Strickland, Sidney
Stress-induced plasticity in the brain requires a precisely orchestrated sequence of cellular events involving novel as well as well known mediators. We have previously demonstrated that tissue plasminogen activator (tPA) in the amygdala promotes stress-induced synaptic plasticity and anxiety-like behavior. Here, we show that tPA activity in the amygdala is up-regulated by a major stress neuromodulator, corticotropin-releasing factor (CRF), acting on CRF type-1 receptors. Compared with WT, tPA-deficient mice responded to CRF treatment with attenuated expression of c-fos (an indicator of neuronal activation) in the central and medial amygdala but had normal c-fos responses in paraventricular nuclei. They exhibited reduced anxiety-like behavior to CRF but had a sustained corticosterone response after CRF administration. This effect of tPA deficiency was not mediated by plasminogen, because plasminogen-deficient mice demonstrated normal behavioral and hormonal changes to CRF. These studies establish tPA as an important mediator of cellular, behavioral, and hormonal responses to CRF.
Bi, Lin-Lin; Sun, Xiang-Dong; Zhang, Jie; Lu, Yi-Sheng; Chen, Yi-Hua; Wang, Jue; Geng, Fei; Liu, Fang; Zhang, Meng; Liu, Ji-Hong; Li, Xiao-Wen; Mei, Lin; Gao, Tian-Ming
Anxiety disorder is related to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The amygdala is important for manifestation and modulation of anxiety. However, relatively little is known regarding the mechanisms that control the amygdala inhibitory activity that is involved in anxiety. We found that almost all ErbB4, which is the only autonomous receptor of neuregulin 1 (NRG1) in the basolateral amygdala (BLA), was expressed in GABAergic neurons. Endogenous NRG1–ErbB4 signaling pathway in the BLA could modulate anxiety-like behaviors and GABA release, whereas it had no effect on glutamatergic transmission. The administration of NRG1 into the BLA of high-anxiety mice alleviated their anxiety and enhanced GABAergic neurotransmission. Moreover, exogenous NRG1 also produced an anxiolytic effect in the stressed mice. Together, these observations indicated that NRG1–ErbB4 signaling is critical to maintaining GABAergic activity in the amygdala and thus to modulating anxiety-like behaviors. Because NRG1 and ErbB4 are susceptibility genes of schizophrenia, our findings might also help to explain the potential mechanism of emotional abnormality in schizophrenia. PMID:25308353
Gilpin, Nicholas W; Henderson, Angela N; Badia-Elder, Nancy E; Stewart, Robert B
Neuropeptide Y (NPY) is abundant in the mammalian brain and plays a prominent role in behaviors related to negative affect and alcohol. NPY suppresses anxiety-like behavior and alcohol-drinking behaviors in a wide array of rodent models and also affects changes in these behaviors produced by fearful and stressful stimuli. Rats selectively bred for high alcohol preference (P rats) appear to be particularly sensitive to the behavioral effects of NPY. The dual purpose of the present investigation was to determine the effects of intraventricular NPY on (1) the acoustic startle response (ASR) of P rats in a high-anxiety setting and (2) social interaction behavior of P rats. In experiment 1, P rats were either cycled through periods of long-term ethanol access and abstinence or they remained ethanol naive. Rats were injected with one of four NPY doses and tested for ASR before and after footshock stress. NPY suppressed ASR in all P rats regardless of shock condition or drinking history. In experiment 2, rats received intraventricular infusion of one of four NPY doses and were then injected with either ethanol (0.75 g/kg) or saline and tested for social interaction. NPY increased social interaction in P rats even at doses that suppressed locomotor activity, regardless of ethanol dose. Suppression of anxiety-like and arousal behaviors by NPY in the present study confirm a role for NPY in alcohol-related behaviors in alcohol-preferring P rats.
Moen, Gro Kvelprud; Støen, Ole-Gunnar; Sahlén, Veronica; Swenson, Jon E
Successful management has brought the Scandinavian brown bear (Ursus arctos L.) back from the brink of extinction, but as the population grows and expands the probability of bear-human encounters increases. More people express concerns about spending time in the forest, because of the possibility of encountering bears, and acceptance for the bear is decreasing. In this context, reliable information about the bear's normal behaviour during bear-human encounters is important. Here we describe the behaviour of brown bears when encountering humans on foot. During 2006-2009, we approached 30 adult (21 females, 9 males) GPS-collared bears 169 times during midday, using 1-minute positioning before, during and after the approach. Observer movements were registered with a handheld GPS. The approaches started 869±348 m from the bears, with the wind towards the bear when passing it at approximately 50 m. The bears were detected in 15% of the approaches, and none of the bears displayed any aggressive behaviour. Most bears (80%) left the initial site during the approach, going away from the observers, whereas some remained at the initial site after being approached (20%). Young bears left more often than older bears, possibly due to differences in experience, but the difference between ages decreased during the berry season compared to the pre-berry season. The flight initiation distance was longer for active bears (115±94 m) than passive bears (69±47 m), and was further affected by horizontal vegetation cover and the bear's age. Our findings show that bears try to avoid confrontations with humans on foot, and support the conclusions of earlier studies that the Scandinavian brown bear is normally not aggressive during encounters with humans.
Cuomo, V; Cagiano, R; Mocchetti, I; Coen, E; Cattabeni, F; Racagni, G
Rats were administered 10 mg/kg SC of clozapine (C) or vehicle solution (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with C or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and C-pretreated rats were investigated. The intensity of stereotyped behaviour as well as the decrement in locomotion induced by apomorphine (0.5--1 mg/kg SC) were not influenced by chronic C administration during development. Finally, at 80 days of age (60 days after the postnatal treatment with C or S was interrupted) rats were subjected to a differential reinforcement of low rates schedule (DRL15s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in S-pretreated rats than in C-pretreated ones. In parallel biochemical experiments, homovanillic acid (HVA) content was measured in striatum in rats at 60 days of age (40 days after the postnatal treatment with C or S was interrupted). The results indicate that even if an acute challenge dose of 10 mg/kg C shows a certain degree of tolerance a single dose of 20 mg/kg C is still able to increase striatal HVA concentration in chronic C-pretreated animals. These data indicate that early postnatal administration of a non-cataleptogenic neuroleptic, like C, induces, in the adult rat, behavioural and biochemical changes which significantly differ from those elicited by a cataleptogenic neuroleptic, like haloperidol.
Raman, Sudha R; Ottensmeyer, C Andrea; Landry, Michel D; Alfadhli, Jarrah; Procter, Steven; Jacob, Susan; Hamdan, Elham; Bouhaimed, Manal
Kuwait mandated seat-belt use by drivers in 1976 and by front seat passengers in 1994. The study objectives were to identify and estimate current factors associated with seat-belt use and levels of potentially unsafe driving behaviours in Kuwait. In 2010, 741 adults were surveyed regarding driving habits and history. Only 41.6% of drivers reported always using a seat belt. Front seat passenger belt use was more common (30.5%) than rear seat belt use (6.5%). Distracted driving behaviours were common, including mobile phone use ('always' or 'almost always': 51.1%) and texting/SMS (32.4%). Logistic regression indicated that drivers who were young (18-19 years), male, Kuwaiti nationals or non-Kuwaiti Arabs, drove over the speed limit, had traffic violation tickets or >1 car crashes in the last year, were less likely to use seat belts. Targeted initiatives to increase public awareness and to enforce car-safety legislation, including use of seat belts, are necessary to decrease the health burden of car crashes in Kuwait.
Background Betel quid chewing is a common habit widely practiced in Southern Asian populations. However, variations are seen in the content of a betel quid across the different countries. Factors associated with commencement and cessation of this habit has been numerously studied. Unfortunately, data on Malaysian population is non-existent. This study aims to determine the factors associated with the inception and also cessation of betel quid chewing behaviour among Malaysian adults. Method This study is part of a nationwide survey on oral mucosal lesions carried out among 11,697 adults in all fourteen states in Malaysia. The questionnaire included sociodemographic information and details on betel quid chewing habit such as duration, type and frequency. The Kaplan-Meier estimates were calculated and plotted to compare the rates for the commencement and cessation of betel quid chewing behaviour. Cox proportional hazard regression models were used to calculate the hazard rate ratios for factors related to commencement or cessation of this habit. Results Of the total subjects, 8.2% were found to be betel quid chewers. This habit was more prevalent among females and, in terms of ethnicity, among the Indians and the Indigenous people of Sabah and Sarawak. Cessation of this habit was more commonly seen among males and the Chinese. Females were found to be significantly more likely to start (p < 0.0001) and less likely to stop the quid chewing habit. Females, those over 40 years old, Indians and a history of smoking was found to significantly increase the likelihood of developing a quid chewing habit (p < 0.0001). However, those who had stopped smoking were found to be significantly more likely to promote stopping the habit (p = 0.0064). Cessation was also more likely to be seen among those who chewed less than 5 quids per day (p < 0.05) and less likely to be seen among those who included areca nut and tobacco in their quid (p < 0.0001). Conclusion Factors that influence
Yamamoto, Ayako; Uchiyama, Koji; Nara, Tomoka; Nishimura, Naomichi; Hayasaka, Michiko; Hanaoka, Kazunori; Yamamoto, Tatsuro
Spock3/Testican-3 is a nervous system-expressed heparan sulfate proteoglycan belonging to a subgroup of the BM-40/SPARC/osteonectin family, the role of which in brain development is unclear. Because Spock1, a member of the Spock family, inhibits their attachment to substrates and the neurite outgrowth of cultured neuronal cells, Spock3 is also thought to be similarly involved in the neuronal development. In the present study, we established a Spock3-mutant mouse harboring a deletion extending from the presumptive upstream regulatory region to exon 4 of the Spock3 locus and performed histological and behavioral studies on these mutant mice. In wild-type (WT) mice, all Spock members were clearly expressed during brain development. In adults, intense Spock1 and Spock2 expressions were observed throughout the entire brain; whereas, Spock3 expression was no longer visible except in the thalamic nuclei. Thus, Spock3 expression is mostly confined to the developmental stage of the brain. In adult mutant mice, the cells of all cortical layers were swollen. The corpus callosum was narrowed around the central region along the rostral-caudal axis and many small spaces were observed without myelin sheaths throughout the entire corpus callosum. In addition, the cortical input and output fibers did not form into thick bundled fibers as well as the WT counterparts did. Moreover, a subpopulation of corticospinal axonal fibers penetrated into the dorsal striatum with moderately altered orientations. Consistent with these modifications of brain structures, the mutant mice exhibited decreased anxiety-like behavior and lowered sociability. Together, these results demonstrate that Spock3 plays an important role in the formation or maintenance of major neuronal structures in the brain.
Davies, Bronwen; Frude, Neil; Jenkins, Rosemary; Harding, Cathy; Hill, Caley
This preliminary study explores the relationships between challenging behaviour and emotional perception in a population of adults with intellectual disabilities, in order to establish whether there are grounds for further study. Cross-sectional data were collected from 96 participants with intellectual disabilities and 95 carers. The service user…
The Good Way model is being used increasingly in New Zealand and Australia in both community-based and residential programmes for the treatment of adolescents and adults with intellectual difficulties who have sexually abusive behaviour. It is also being used with children and, in adapted forms, with mainstream adolescents and people of indigenous…
Zhao, Fei; French, David; Manchaiah, Vinaya K.C.; Liang, Maojin; Price, Sharon M.
Introduction: Adolescents and young adults have been shown to be the age group most at risk of music-induced hearing loss (MIHL), which is already evident and increasing among this group. Objective: The purpose of this review is to provide further insight into the effectiveness of education programmes on attitude and behaviour towards loud music…
Campbell, Martin; McCue, Michael
A new risk assessment tool, "Assessment of Interpersonal Risk" (AIR), was piloted and evaluated to measure risk factors and compatibility between individuals living in an assessment and treatment unit in one NHS area. The adults with learning disabilities in this unit had severe and enduring mental health problems and/or behaviour that is severely…
Sohanpal, S. K.; Deb, S.; Thomas, C.; Soni, R.; Lenotre, L.; Unwin, G.
Background: A comprehensive systematic review was performed to establish the current evidence base regarding the effectiveness of antidepressant medication for the management of behaviour problems in adults with intellectual disabilities. Method: An electronic search of PsycInfo, Embase, Medline and Cinahl databases was conducted spanning the time…
Hippolyte, L.; Iglesias, K.; Van der Linden, M.; Barisnikov, K.
Background: Although the prevalence of mental illness and behaviour problems is lower in adults with Down syndrome (DS) than in other populations with intellectual disabilities, they do present emotional and relational problems, as well as social integration difficulties. However, studies reporting on specific competences known to be central in…
Burgess, E; Hassmén, P; Welvaert, M; Pumpa, K L
Poor adherence to lifestyle intervention remains a key factor hindering treatment effectiveness and health outcomes for adults with obesity. The aim of this systematic review and meta-analysis is to determine if behavioural treatment strategies (e.g. goal setting, motivational interviewing, relapse prevention, cognitive restructuring etc.) improve adherence to lifestyle intervention programmes in adults with obesity. Randomized controlled trials that investigated the use of behavioural treatment strategies in obesity management were identified by systematically reviewing the literature within Medline, PsycINFO, CINAHL, SPORTDiscus and Web of Science from their inception to August 2016. This meta-analysis shows that behavioural treatment interventions have a significant positive effect on session attendance (percentage) and physical activity (total min/week) in adults with obesity (M = 17.63 (95% confidence interval (CI) = 10.77, 24.50), z =5.0337, P < 0.0001 and M = 105.98 (95% CI = 58.64, 153.32), z =4.3878, P < 0.0001, respectively). This meta-analysis of randomized controlled trials provides evidence that behavioural treatment strategies improve adherence to lifestyle intervention programmes in adults with obesity. These strategies should be routinely incorporated into lifestyle intervention, obesity management and weight loss programmes with the aim of improving engagement and adherence. If adherence were improved, treatment effectiveness, health outcomes and the ultimate burden of chronic disease could also be improved.
Tsakanikos, Elias; Costello, Helen; Holt, Geraldine; Sturmey, Peter; Bouras, Nick
We examined behaviour management problems as predictors of psychotropic medication, use of psychiatric consultation and in-patient admission in a group of 66 adults with pervasive developmental disorder (PDD) and intellectual disability (ID) and 99 controls matched in age, gender and level of ID. Overall, people with PDD had higher rates of most…
Tsakanikos, Elias; Costello, Helen; Holt, Geraldine; Sturmey, Peter; Bouras, Nick
We examined behaviour management problems as predictors of psychotropic medication, use of psychiatric consultation and in-patient admission in a group of 66 adults with pervasive developmental disorder (PDD) and intellectual disability (ID) and 99 controls matched in age, gender and level of ID. Overall, people with PDD had higher rates of most DAS behaviour problems and more frequent use of anti-psychotics than matched controls. Logistic regression analyses showed that physical aggression and problems such as pestering staff independently predicted use of anti-psychotics. Physical aggression and overactivity predicted further involvement of psychiatric services. PDD diagnosis predicted admission to an in-patient unit. The results suggest that externalizing problem behaviours in adults with autism can predict type of treatment intervention.
Robertson, Annaleise; Mullan, Barbara; Todd, Jemma
While rates of obesity continue to increase, weight-loss interventions to date have not been hugely successful. The purpose of this study was to explore the specific factors that are relevant to weight control in overweight and obese young adults compared to older adults, within the context of the theory of planned behaviour (TPB). A qualitative methodology with purposive sampling was used. Semi-structured interviews were conducted with 23 young adults and older adults who were currently overweight or obese. The research was informed by thematic analysis. A mixed deductive-inductive approach that was structured around but not limited to TPB constructs was applied. Themes mapped onto the TPB behaviour well, with additional themes of motivation, and knowledge and experience emerging. Differences across groups included motivators to weight loss (e.g. appearance and confidence for young adults, health for older adults), importance of social influences, and perceptions of control (e.g. availability and cost for young adults, age and energy for older adults). Similarities across groups included attitudes towards being overweight and losing weight, and the value of preparation and establishment of a healthy routine. Finally, across both groups, knowledge and confidence in ability to lose weight appeared adequate, despite failed attempts to do so. The different experiences identified for younger and older adults can be used to inform future tailored weight-loss interventions that are relevant to these age groups, and the TPB could provide a useful framework. Additional intervention strategies, such as improving behavioural routine and improving self-regulation also warrant further investigation.
Coutellier, Laurence; Friedrich, Anne-Christin; Failing, Klaus; Würbel, Hanno
According to the maternal mediation hypothesis, brain and behavioural development in rodents is affected by environment-dependent variations in maternal care. Thus, it has been shown that early handling results in reduced behavioural and neuroendocrine responses to stressors and that these effects are associated with increased maternal care received during infancy. To investigate this further in mice, we chose a less artificial paradigm that is not confounded by human manipulation and reflects a more natural form of early environmental variation. We housed lactating C57BL/6 dams and their litters in cage systems composed of a nest cage (NC) and a foraging cage (FC) connected by a tunnel, and varied the dams' access to food by providing food either in the NC (NC dams) or FC (FC dams) until postnatal day 14. FC dams were more frequently observed in the FC than NC dams, and although the frequency of the dams being in physical contact with the pups did not differ between the two treatments, FC dams showed lower levels of active nursing than NC dams during the first week of lactation. These environment-dependent variations in maternal behaviour had sex-specific effects on the adult offspring's behavioural and HPA responses to stressors and altered their social behaviour in the home cage, with NC offspring showing higher levels of socio-positive behaviours than FC offspring. These results provide further independent evidence for the maternal mediation hypothesis and demonstrate that even subtle variations of the maternal environment can affect maternal care and induce persistent changes in offspring phenotype.
Osborn, C. Y.; Mayberry, L. S.; Kim, J. M.
SUMMARY What is known Patients with type 2 diabetes mellitus (T2DM) are required to perform multiple self-care behaviours to achieve and maintain optimal glycaemic control (HbA1c), which prevents complications and premature mortality. Patients with T2DM and low socioeconomic status (SES) are more likely to have suboptimal HbA1c, often due to being less adherent to recommended self-care activities than their higher-SES counterparts. Objective Although studies support performing certain diabetes self-care behaviours for optimizing glycaemic control, there is limited research on the relative importance of each behaviour for this purpose. Identifying what behaviours are most important for HbA1c among low-SES patients with T2DM would be particularly useful for informing policy and intervention efforts for this high-risk group. Methods In a cross-sectional study of 314 adults with T2DM and low SES, we used the Summary of Diabetes Self-Care Activities to assess self-care behaviours and multivariate models to test which behaviours were associated with lower HbA1c. Results and discussion Only medication adherence was significantly associated with lower HbA1c after adjusting for the other self-care behaviours (β = −0 14, P = 0 028) and further adjusting for demographic and diabetes characteristics (β = −0 16, P = 0 024). What is new Medication adherence may be the most important self-care behaviour for glycaemic control among adults with T2DM and low SES. Conclusion Focused efforts to improve medication adherence among low-SES patient populations may improve glycaemic control. PMID:26939721
DuBois, C; Zakrajsek, E; Haley, D B; Merkies, K
Examining the characteristics of an animal's lying behaviour, such as frequency and duration of lying bouts, has become increasingly relevant for animal welfare research. Triaxial accelerometers have the advantage of being able to continuously monitor an animal's standing and lying behaviour without relying on live observations or video recordings. Multiple models of accelerometers have been validated for use in monitoring dairy cattle; however, no units have been validated for use in equines. This study tested Onset Pendant G data loggers attached to the hind limb of each of two mature Standardbred horses for a period of 5 days. Data loggers were set to record their position every 20 s. Horses were monitored via live observations during the day and by video recordings during the night to compare activity against accelerometer data. All lying events occurred overnight (three to five lying bouts per horse per night). Data collected from the loggers was converted and edited using a macro program to calculate the number of bouts and the length of time each animal spent lying down by hour and by day. A paired t-test showed no significant difference between the video observations and the output from the data loggers (P=0.301). The data loggers did not distinguish standing hipshot from standing square. Predictability, sensitivity, and specificity were all >99%. This study has validated the use of Onset Pendant G data loggers to determine the frequency and duration of standing and lying bouts in adult horses when set to sample and register readings at 20 s intervals.
Alsiö, J; Roman, E; Olszewski, P K; Jonsson, P; Fredriksson, R; Levine, A S; Meyerson, B J; Hulting, A-L; Lindblom, J; Schiöth, H B
The aim of this study was to investigate whether the preference for a palatable high-fat diet (HFD) is associated with response to novelty and with anxiety-like behavior in rats and whether such fat preference correlates with gene expression of hypothalamic neuropeptides related to feeding. We subjected male rats to two tests of exploration of novel environments: the multivariate concentric square field (MCSF) and the elevated plus maze (EPM). The rats were then exposed to a 5-day test of preference for a palatable HFD versus reference diets. Messenger RNA (mRNA) levels of 21 neuropeptides were investigated by quantitative polymerase chain reaction. We found a strong positive correlation of HFD preference and open-arm activity in the EPM (% open-arm time, r(s) = 0.629, df = 26, P < 0.001). Thus, HFD preference was inversely associated with anxiety-like behavior. The same association was found for HFD preference and behavior in the MCSF (bridge entries, r(s) = 0.399, df = 23, P = 0.048). In addition, the HFD preference was positively correlated (r(s) = 0.433, df = 25, P = 0.021) with hypothalamic mRNA levels of urocortin 2 (Ucn 2). Moreover, behavior in the EPM was significantly correlated with expression levels of the receptor for Ucn 2, the corticotropin-releasing factor receptor 2, in the hypothalamus (r(s) = 0.382, df = 33, P = 0.022, pituitary (r(s) = 0.494, df = 31, P = 0.004) and amygdala (r(s) = 0.381, df = 30, P = 0.032). We conclude that preference for palatable HFD is inversely associated with anxiety and propose that Ucn 2 signaling may play a role in this association.
Chen, Chieh V; Brummet, Jennifer L; Lonstein, Joseph S; Jordan, Cynthia L; Breedlove, S Marc
Men are less likely than women to suffer from anxiety disorders. Because gonadal hormones play a crucial role in many behavioral sex differences, they may underlie sex differences in human anxiety. In rodents, testosterone (T) exerts anxiolytic effects via the androgen receptor (AR): we found that male mice with a naturally-occurring mutation rendering the AR dysfunctional, referred to as spontaneous testicular feminization mutation (sTfm), showed more anxiety-like behaviors than wildtype (WT) males. Here, we used Cre-lox recombination technology to create another dysfunctional allele for AR. These induced Tfm (iTfm) animals also displayed more anxiety-like behaviors than WTs. We further found that AR-modulation of these behaviors interacts with circadian phase. When tested in the resting phase, iTfms appeared more anxious than WTs in the open field, novel object and elevated plus maze tests, but not the light/dark box. However, when tested during the active phase (lights off), iTfms showed more anxiety-related behavior than WTs in all four tests. Finally, we confirmed a role of T acting via AR in regulating HPA axis activity, as WT males with T showed a lower baseline and overall corticosterone response, and a faster return to baseline following mild stress than did WT males without T or iTfms. These findings demonstrate that this recombined AR allele is a valuable model for studying androgenic modulation of anxiety, that the anxiolytic effects of AR in mice are more prominent in the active phase, and that HPA axis modulation by T is AR dependent.
Fedotova, Julia; Soultanov, Vagif; Nikitina, Tamara; Roschin, Victor; Ordyan, Natalia; Hritcu, Lucian
Previous studies indicated that reduced androgen levels may contribute to both physical and cognitive disorders in men, including Alzheimer's disease. New drug candidates for Alzheimer's disease in patients with androgen deficiency should ideally be able to act not only on multiple brain targets but also to correct impaired endocrine functions in hypogonadal men with Alzheimer's disease. Ropren(®) is one such candidate for the treatment of Alzheimer's disease in men with an imbalance of androgens. Accordingly, the aim of the current study was to examine the effects of long-term Ropren(®) administration (8.6mg/kg, orally, once daily, for 28 days) on the anxiety-like behavior and monoamines levels in the rat hippocampus using a β-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. Ropren(®) was administered to the gonadectomized (GDX) rats and GDX rats treated with testosterone propionate (TP, 0.5mg/kg, subcutaneous, once daily, for 28 days). Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark test (LDT), locomotor and grooming activities were assessed in the open field test (OFT). Ropren(®) alone or in combination with TP-induced anxiolytic effects as evidenced in the EPM and in the LDT and increased locomotor activity in the OFT. Additionally, it was observed that dopamine (DA) and serotonin (5-HT) levels increased while 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio in the hippocampus decreased. Our results indicate that Ropren(®) has a marked anxiolytic-like action due to an increase in the monoamines levels in the experimental rat model of Alzheimer's disease with altered levels of androgens.
Bjørge, Monica D; Hildrestrand, Gunn A; Scheffler, Katja; Suganthan, Rajikala; Rolseth, Veslemøy; Kuśnierczyk, Anna; Rowe, Alexander D; Vågbø, Cathrine B; Vetlesen, Susanne; Eide, Lars; Slupphaug, Geir; Nakabeppu, Yusaku; Bredy, Timothy W; Klungland, Arne; Bjørås, Magnar
Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic DNA lesion associated with cognitive decline. We have examined behavior and cognitive function in mice deficient of these glycosylases. Ogg1(-/-)Mutyh(-/-) mice were more active and less anxious, with impaired learning ability. In contrast, Mutyh(-/-) mice showed moderately improved memory. We observed no apparent change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutants belong to pathways known to be involved in anxiety and cognition. Esr1 targets were upregulated, suggesting a role of Ogg1 and Mutyh in repression of Esr1 signaling. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh regulate hippocampal gene expression related to cognition and behavior, suggesting a role for the glycosylases in regulating adaptive behavior.
Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne
Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This preliminary randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive behavioural therapy and recreational activity. Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6-8 patients. A total of 68 psychiatric patients with autism spectrum disorders participated in the study. Outcome measures were Quality of Life Inventory, Sense of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health. Participants in both treatment conditions reported an increased quality of life at post-treatment (d = 0.39, p < 0.001), with no difference between interventions. No amelioration of psychiatric symptoms was observed. The dropout rate was lower with cognitive behavioural therapy than with recreational activity, and participants in cognitive behavioural therapy rated themselves as more generally improved, as well as more improved regarding expression of needs and understanding of difficulties. Both interventions appear to be promising treatment options for adults with autism spectrum disorder. The interventions' similar efficacy may be due to the common elements, structure and group setting. Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout.
Plenty, Stephanie; Bejerot, Susanne
Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This preliminary randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive behavioural therapy and recreational activity. Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6–8 patients. A total of 68 psychiatric patients with autism spectrum disorders participated in the study. Outcome measures were Quality of Life Inventory, Sense of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health. Participants in both treatment conditions reported an increased quality of life at post-treatment (d = 0.39, p < 0.001), with no difference between interventions. No amelioration of psychiatric symptoms was observed. The dropout rate was lower with cognitive behavioural therapy than with recreational activity, and participants in cognitive behavioural therapy rated themselves as more generally improved, as well as more improved regarding expression of needs and understanding of difficulties. Both interventions appear to be promising treatment options for adults with autism spectrum disorder. The interventions’ similar efficacy may be due to the common elements, structure and group setting. Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout. PMID:24089423
Behavioural treatments (predominantly biofeedback, relaxation and cognitive-behavioural) have been utilised in headache management for nearly 4 decades. This paper examines their clinical efficacy, drawing upon 2 primary sources of evidence: meta-analytic and evidenced-based reviews. Behavioural treatments have demonstrated efficacy and have been endorsed by various reviewing groups, such as the US Headache Consortium. Outcomes from behavioural treatments appear to endure over longer-term follow-up intervals as well. Meta-analyses comparing behavioural and pharmacological treatments have revealed similar levels of outcome. The article closes with a brief discussion of methods investigators are exploring to make behavioural treatments more available and affordable to headache patients.
Harris, Petra; Loveman, Emma; Clegg, Andy; Easton, Simon; Berry, Neil
Aim: This systematic review aimed to establish if cognitive behavioural therapy (CBT) can reduce the physical symptoms of chronic headache and migraines in adults. Methods: Evidence from searches of eight databases was systematically sought, appraised and synthesised. Screening of title and abstracts was conducted independently by two reviewers. Full papers were screened, data extracted and quality assessed by one reviewer and checked by a second. Data were synthesised narratively by intervention due to the heterogeneity of the studies. The inclusion criteria specified randomised controlled trials with CBT as an intervention in adults suffering from chronic headaches/migraines not associated with an underlying pathology/medication overuse. CBT was judged on the basis of authors describing the intervention as CBT. The diagnosis of the condition had to be clinician verified. Studies had to include a comparator and employ headache/migraine-specific outcomes such as patient-reported headache days. Results: Out of 1126 screened titles and abstracts and 20 assessed full papers, 10 studies met the inclusion criteria of the review. Some studies combined CBT with another intervention, as well as employing varying numbers of comparators. CBT was statistically significantly more effective in improving some headaches-related outcomes in CBT comparisons with waiting lists (three studies), in combination with relaxation compared with relaxation only (three studies) or antidepressant medication (one study), with no statistically significant differences in three studies. Conclusions: The findings of this review were mixed, with some studies providing evidence in support of the suggestion that people experiencing headaches or migraines can benefit from CBT, and that CBT can reduce the physical symptoms of headache and migraines. However, methodology inadequacies in the evidence base make it difficult to draw any meaningful conclusions or to make any recommendations. PMID:26526604
Newark, Patricia Elizabeth; Stieglitz, Rolf-Dieter
Adult individuals with attention-deficit hyperactivity disorder (ADHD) have been suffering from this neurobiological and highly heritable disorder chronically since childhood. Resulting from their longstanding neuropsychological impairments, such as attentional problems, emotional instability, and disinhibition, they are familiar to a multiplicity of negative life outcomes and underachievement. Furthermore, a large part of this population suffers from psychiatric comorbidity. This accumulation of negative experiences has an impact on therapy-relevant factors such as the individual's self-esteem, self-efficacy, development of core beliefs/schemas, and coping strategies. Based on negative beliefs about the self, individuals confronted with difficult situations develop maladaptive coping strategies, for instance avoidance and procrastination. These strategies lead to maintenance and reinforcement of maladaptive beliefs, and as such they acquit themselves as schema-confirming. Captured in this vicious cycle, the individual sees her negative view of the self confirmed. The purpose of this paper is to illuminate these interactive factors that influence the aforementioned cycle in order to emphasize the cognitive behavioural interventions tailored to those factors on the basis of latest research. Furthermore, the authors want to attract notice to the resources people with ADHD are said to have, namely creativity and resilience. These postulated resources could be therapy-relevant by creating positive beliefs about the self, hence improving coping skills and breaking the vicious circle of negative appraisal. Taking into account personal resources and their fostering may be an important fundament for the treatment plan of adult ADHD. Information on the current state of research and theoretical approaches concerning the below-mentioned key words was gathered through MEDLINE, PsycINFO, PSYNDEXplus, and PubMed databases.
Turner, Karly M.; Eyles, Darryl W.; McGrath, John J.; Burne, Thomas H. J.
Background Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Methods Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. Results AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8–10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. Conclusions AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour. PMID:23951200
Tak, Sanne R; Hendrieckx, Christel; Nefs, Giesje; Nyklíček, Ivan; Speight, Jane; Pouwer, François
Although healthy food choices are important in the management of diabetes, making dietary adaptations is often challenging. Previous research has shown that people with type 2 diabetes are less likely to benefit from dietary advice if they tend to eat in response to emotions or external cues. Since high levels of dispositional mindfulness have been associated with greater awareness of healthy dietary practices in students and in the general population, it is relevant to study the association between dispositional mindfulness and eating behaviour in people with type 1 or 2 diabetes. We analysed data from Diabetes MILES - The Netherlands, a national observational survey in which 634 adults with type 1 or 2 diabetes completed the Dutch Eating Behaviour Questionnaire (to assess restrained, external and emotional eating behaviour) and the Five Facet Mindfulness Questionnaire-Short Form (to assess dispositional mindfulness), in addition to other psychosocial measures. After controlling for potential confounders, including demographics, clinical variables and emotional distress, hierarchical linear regression analyses showed that higher levels of dispositional mindfulness were associated with eating behaviours that were more restrained (β = 0.10) and less external (β = -0.11) and emotional (β = -0.20). The mindfulness subscale 'acting with awareness' was the strongest predictor of both external and emotional eating behaviour, whereas for emotional eating, 'describing' and 'being non-judgemental' were also predictive. These findings suggest that there is an association between dispositional mindfulness and eating behaviour in adults with type 1 or 2 diabetes. Since mindfulness interventions increase levels of dispositional mindfulness, future studies could examine if these interventions are also effective in helping people with diabetes to reduce emotional or external eating behaviour, and to improve the quality of their diet.
Francisco, Elian da Silva; Guedes, Rubem Carlos Araújo
The amino acids taurine and alanine play a role in several physiological processes, including behavior and the electrical activity of the brain. In this study, we investigated the effect of treatment with taurine or alanine on anxiety-like behavior and the excitability-dependent phenomenon known as cortical spreading depression (CSD), using rats suckled in litters with 9 and 15 pups (groups L9 and L15). From postnatal days 7 to 27, the animals received per gavage 300 mg/kg/day of taurine or alanine or both. At 28 days, we tested the animals in the elevated plus maze, and at 33-35 days, we recorded CSD and analyzed its velocity of propagation, amplitude, and duration. Compared with water-treated controls, the L9 groups treated with taurine or alanine displayed anxiolytic behavior (higher number of entries in the open arms; p < 0.05), and reduced CSD velocity (p < 0.001). The effect of both amino acids on CSD was also found in the L15 groups and in five additional L9 groups (naïve, water, taurine, alanine, or both) treated at adulthood (90-110 days). The L15 condition resulted in smaller durations and higher CSD velocities compared with the L9 condition. Besides reinforcing previous evidence of behavioral modulation by taurine and alanine, our data are the first confirmation that treatment with these amino acids decelerates CSD regardless of lactation conditions (normal versus unfavorable lactation) or age at amino acid administration (young versus adult). The results suggest a modulating role for both amino acids on anxiety behavior and neuronal electrical activity.
Villagra, Cristian A.; Pennacchio, Francesco; Niemeyer, Hermann M.
The relevance of the integration of preimaginal and eclosion experiences on the subsequent habitat preferences and mate finding by the adult has been rarely tested in holometabolous insects. In this work, the effect of larval and early adult experiences on the behavioural responses of adult males of the aphid parasitoid, Aphidius ervi, towards volatiles from the host-plant complex (HPC) and from conspecific females were evaluated. Two experience factors were considered: host diet (normal diet=ND; artificial diet=AD), and eclosion, i.e. extraction or non-extraction of the parasitoid larva from the parasitised aphid (extracted=EX; non-extracted=NE). Thus, four treatments were set up: ND/NE, ND/EX, AD/NE and AD/EX. Glass Y-tube olfactometers were used to investigate the responses of adult A. ervi males to the odour sources used. Males from the ND/NE treatment showed a shorter latency to the first choice of olfactometer arms, displayed a marked preference towards the HPC olfactometer arm, and spent more time in the HPC arm than males from the other treatments. Only the interaction of host diet and eclosion experiences proved to be relevant in explaining the differences in latency to first choice, time spent in olfactometers arms, and behaviours displayed in the olfactometer arms. These results show the importance of the integration of larval and eclosion experiences in the development of stereotyped responses of the adults. This process may involve memory retention from the preimaginal and emergence period, but further research is needed to disentangle the contribution of each stage. The response to conspecific females was much less affected by the treatments in relation to first arm choice and times in olfactometer arms, suggesting a pheromone-mediated behaviour, even though a prompter and more intense wing fanning courtship behaviour was registered in the ND/NE males compared to males from the AD/NE treatment. These results show that sexual behaviours are less
Mishra, Rachana; Manchanda, Shaffi; Gupta, Muskan; Kaur, Taranjeet; Saini, Vedangana; Sharma, Anuradha; Kaur, Gurcharan
Sleep deprivation (SD) leads to the spectrum of mood disorders like anxiety, cognitive dysfunctions and motor coordination impairment in many individuals. However, there is no effective pharmacological remedy to negate the effects of SD. The current study examined whether 50% ethanolic extract of Tinospora cordifolia (TCE) can attenuate these negative effects of SD. Three groups of adult Wistar female rats - (1) vehicle treated-sleep undisturbed (VUD), (2) vehicle treated-sleep deprived (VSD) and (3) TCE treated-sleep deprived (TSD) animals were tested behaviorally for cognitive functions, anxiety and motor coordination. TSD animals showed improved behavioral response in EPM and NOR tests for anxiety and cognitive functions, respectively as compared to VSD animals. TCE pretreatment modulated the stress induced-expression of plasticity markers PSA-NCAM, NCAM and GAP-43 along with proteins involved in the maintenance of LTP i.e., CamKII-α and calcineurin (CaN) in hippocampus and PC regions of the brain. Interestingly, contrary to VSD animals, TSD animals showed downregulated expression of inflammatory markers such as CD11b/c, MHC-1 and cytokines along with inhibition of apoptotic markers. This data suggests that TCE alone or in combination with other memory enhancing agents may help in managing sleep deprivation associated stress and improving cognitive functions. PMID:27146164
Maia-Carneiro, Thiago; Rocha, Carlos Frederico Duarte
Adaptations of lizards inhabiting hot arid environments should include mechanisms of behavioural thermoregulation. In contrast, in environments with lower temperatures lizards tend to behave as thermoconformers. Herein we aim to infer thermoregulatory behaviours exhibited by Liolaemus lutzae (a lizard species endemic to restingas in the coast of the state of Rio de Janeiro, Brazil) in two different seasonal thermal environments. In the dry season, the body temperatures (Tb) of the lizards were higher than air temperature (Ta) and similar to substrate temperature (Ts), suggesting thermoconformer thermoregulatory behaviour using Ts. During the rainy season, the higher percentage of negative values of ΔTs (=Tb-Ts) and ΔTa (=Tb-Ta) and the tendency for lower Tb compared to Ts suggest a more active behavioural thermoregulation in that season. The ΔTs was higher for juveniles in the rainy season, suggesting that youngest lizards tended to thermoregulate more actively regarding to Ts than adults. L. lutzae probably survives under high Ts due to the behaviour of the individuals sheltering inside burrows or under detritus and burying themselves into the sand. This behavioural flexibility may potentially reduce variations in Tb of active lizards in changing thermal environments both during the daily cycle and between seasons.
Matson, Johnny L.; Rivet, Tessa T.
Background: Challenging behaviours are frequently a problem for people with autism spectrum disorders (ASD) and intellectual disability (ID). A better understanding of which individuals display which behaviours, at what rates, and the relationship of these behaviours to comorbid psychopathology would have important implications. Method: A group of…
Adams, D.; Oliver, C.; Kalsy, S.; Peters, S.; Broquard, M.; Basra, T.; Konstandinidi, E.; McQuillan, S.
Background: Behavioural changes associated with dementia in Down syndrome are well documented, yet little is known about the effect of such behaviours on carers and referral. By comparing the behavioural and cognitive profiles of individuals referred for a dementia assessment with those of individuals not referred, some insight can be gained into…
Bot, Sandra D.; Mackenbach, Joreintje D.; Nijpels, Giel; Lakerveld, Jeroen
Objectives In this exploratory study we examined the associations between several social network characteristics and lifestyle behaviours in adults at increased risk of diabetes and cardiovascular diseases. In addition, we explored whether similarities in lifestyle between individuals and their network members, or the level of social support perceived by these individuals, could explain these associations. Methods From the control group of the Hoorn Prevention Study, participants with high and low educational attainment were approached for a structured interview between April and August 2010. Inclusion was stopped when fifty adults agreed to participate. Participants and a selection of their network members (e.g. spouses, best friends, neighbours, colleagues) completed a questionnaire on healthy lifestyle that included questions on fruit and vegetable intake, daily physical activity and leisure-time sedentary behaviour. We first examined associations between network characteristics and lifestyle using regression analyses. Second, we assessed associations between network characteristics and social support, social support and lifestyle, and compared the participants’ lifestyles to those of their network members using concordance correlation coefficients. Results Fifty adults (50/83 x 100 = 62% response) and 170 of their network members (170/192 x 100 = 89% response) participated in the study. Individuals with more close-knit relationships, more friends who live nearby, and a larger and denser network showed higher levels of vegetable consumption and physical activity, and lower levels of sedentary behaviour. Perceived social norms or perceived support for behavioural change were not related to healthy lifestyle. Except for spousal concordance for vegetable intake, the lifestyle of individuals and their network members were not alike. Conclusions Study results suggest that adults with a larger and denser social network have a healthier lifestyle. Underlying
Payne, Jennifer Shepard; Galvan, Frank H; Williams, John K; Prusinski, Missy; Zhang, Muyu; Wyatt, Gail E; Myers, Hector F
Adult men of different ethnic backgrounds who experienced childhood sexual abuse (CSA) may vary in their reports of the psychological and behavioural impact of CSA on their lives. Empirical studies rarely examine the impact of race/ethnicity or cultural context on the psychological and behavioural struggles of adult male CSA survivors. This study utilised qualitative content analysis to examine the reported CSA-related psychological and behavioural challenges of 150 US men, with equal numbers of Blacks, Latinos and non-Latino Whites. Interview data revealed some ethnic differences: Black men more frequently denied having present day adverse effects than other groups. However, Black men who did report negative consequences of CSA discussed difficulties with substance use and hyper-sexualised behaviour more often than other ethnicities. Latino men reported anger, anxiety, hyper-vigilance, flashbacks and communication problems more often than the other two groups. Black and Latino men also discussed guilt/shame issues and sexual identity concerns more often than Whites did. In contrast, White men more frequently discussed issues related to low self-esteem, loneliness and isolation. These findings suggest that ethnically diverse men may respond differently to CSA experiences and that considerations need to be taken into account when providing healthcare to men with CSA histories.
Galvan, Frank H.; Williams, John K.; Prusinski, Missy; Zhang, Muyu; Wyatt, Gail E.; Myers, Hector F.
Adult men of different ethnic backgrounds who experienced childhood sexual abuse (CSA) may vary in their reports of the psychological and behavioural impact of CSA on their lives. Empirical studies rarely examine the impact of race/ethnicity or cultural context on the psychological and behavioural struggles of adult male CSA survivors. This study utilised qualitative content analysis to examine the reported CSA-related psychological and behavioural challenges of 150 U.S. men, with equal numbers of Blacks, Latinos, and non-Latino Whites. Interview data revealed some ethnic differences: Black men more frequently denied having present day adverse effects than other groups. However, Black men who did report negative consequences of CSA discussed difficulties with substance use and hyper-sexualised behaviour more often than other ethnicities. Latino men reported anger, anxiety, hyper-vigilance, flashbacks and communication problems more often than the other two groups. Black and Latino men also discussed guilt/shame issues and sexual identity concerns more often than Whites did. In contrast, White men more frequently discussed issues related to low self-esteem, loneliness and isolation. These findings suggest that ethnically diverse men may respond differently to CSA experiences and that considerations need to be taken into account when providing health care to men with CSA histories. PMID:24393013
Nascimento, Marcus; Silva, Danielle; Ribeiro, Sandra; Nunes, Marco; Almeida, Marcos; Mendes-Netto, Raquel
The objective of the present study is to evaluate and compare the effect of a nutritional intervention between adolescent and adult. In a before and after quasi-experimental clinical study, 32 athletes (21 adults, age range 20-32 years; 11 adolescents, age range: 12-19 years) participated in a nutritional counselling consisting of four consultations separated by an interval of 45 to 60 days. The athlete's eating behaviour, body composition and nutrition knowledge were evaluated at the beginning and at the end of the protocol. Both groups increased lean body mass and nutritional knowledge. Adolescents increased their mid-arm muscle circumference and improved meal frequency, and daily water intake. Athletes of both groups improved their ingestion of vegetables and fruits and decreased the ingestion of sweets and oils. Adolescents showed a higher prevalence of individuals that remained within or approached to the recommendations of sweets. This is the first study to evaluate and compare the effect of a nutritional intervention between adolescent and adult athletes body composition, eating behaviour and nutritional knowledge. The nutritional counselling has been effective in promoting beneficial changes on the athlete's eating behaviour, nutritional knowledge and body composition, however, some healthy changes were only experienced by adolescents, especially in the frequency of meals and the intake of sweets.
Yoshikawa, Takeo; Nakamura, Tadaho; Shibakusa, Tetsuro; Sugita, Mayu; Naganuma, Fumito; Iida, Tomomitsu; Miura, Yamato; Mohsen, Attayeb; Harada, Ryuichi; Yanai, Kazuhiko
L-histidine is one of the essential amino acids for humans, and it plays a critical role as a component of proteins. L-histidine is also important as a precursor of histamine. Brain histamine is synthesized from L-histidine in the presence of histidine decarboxylase, which is expressed in histamine neurons. In the present study, we aimed to elucidate the importance of dietary L-histidine as a precursor of brain histamine and the histaminergic nervous system. C57BL/6J male mice at 8 wk of age were assigned to 2 different diets for at least 2 wk: the control (Con) diet (5.08 g L-histidine/kg diet) or the low L-histidine diet (LHD) (1.28 g L-histidine/kg diet). We measured the histamine concentration in the brain areas of Con diet-fed mice (Con group) and LHD-fed mice (LHD group). The histamine concentration was significantly lower in the LHD group [Con group vs. LHD group: histamine in cortex (means ± SEs): 13.9 ± 1.25 vs. 9.36 ± 0.549 ng/g tissue; P = 0.002]. Our in vivo microdialysis assays revealed that histamine release stimulated by high K(+) from the hypothalamus in the LHD group was 60% of that in the Con group (P = 0.012). However, the concentrations of other monoamines and their metabolites were not changed by the LHD. The open-field tests showed that the LHD group spent a shorter amount of time in the central zone (87.6 ± 14.1 vs. 50.0 ± 6.03 s/10 min; P = 0.019), and the light/dark box tests demonstrated that the LHD group spent a shorter amount of time in the light box (198 ± 8.19 vs. 162 ± 14.1 s/10 min; P = 0.048), suggesting that the LHD induced anxiety-like behaviors. However, locomotor activity, memory functions, and social interaction did not differ between the 2 groups. The results of the present study demonstrated that insufficient intake of histidine reduced the brain histamine content, leading to anxiety-like behaviors in the mice.
Kourouniotis, S; Keast, R S J; Riddell, L J; Lacy, K; Thorpe, M G; Cicerale, S
The 'taste of food' plays an important role in food choice. Furthermore, foods high in fat, sugar and salt are highly palatable and associated with increased food consumption. Research exploring taste importance on dietary choice, behaviour and intake is limited, particularly in young adults. Therefore, in this study a total of 1306 Australian university students completed questionnaires assessing dietary behaviors (such as how important taste was on food choice) and frequency of food consumption over the prior month. Diet quality was also assessed using a dietary guideline index. Participants had a mean age of 20 ± 5 years, Body Mass Index (BMI) of 22 ± 3 kg/m(2), 79% were female and 84% Australian. Taste was rated as being a very or extremely important factor for food choice by 82% of participants. Participants who rated taste as highly important, had a poorer diet quality (p = 0.001) and were more likely to consume less fruit (p = 0.03) and vegetables (p = 0.05). Furthermore, they were significantly more likely to consume foods high in fat, sugar and salt, including chocolate and confectionary, cakes and puddings, sweet pastries, biscuits, meat pies, pizza, hot chips, potato chips, takeaway meals, soft drink, cordial and fruit juice (p = 0.001-0.02). They were also more likely to consider avoiding adding salt to cooking (p = 0.02) and adding sugar to tea or coffee (p = 0.01) as less important for health. These findings suggest that the importance individuals place on taste plays an important role in influencing food choice, dietary behaviors and intake.
Rotics, Shay; Kaatz, Michael; Resheff, Yehezkel S; Turjeman, Sondra Feldman; Zurell, Damaris; Sapir, Nir; Eggers, Ute; Flack, Andrea; Fiedler, Wolfgang; Jeltsch, Florian; Wikelski, Martin; Nathan, Ran
Migration conveys an immense challenge, especially for juvenile birds coping with enduring and risky journeys shortly after fledging. Accordingly, juveniles exhibit considerably lower survival rates compared to adults, particularly during migration. Juvenile white storks (Ciconia ciconia), which are known to rely on adults during their first fall migration presumably for navigational purposes, also display much lower annual survival than adults. Using detailed GPS and body acceleration data, we examined the patterns and potential causes of age-related differences in fall migration properties of white storks by comparing first-year juveniles and adults. We compared juvenile and adult parameters of movement, behaviour and energy expenditure (estimated from overall dynamic body acceleration) and placed this in the context of the juveniles' lower survival rate. Juveniles used flapping flight vs. soaring flight 23% more than adults and were estimated to expend 14% more energy during flight. Juveniles did not compensate for their higher flight costs by increased refuelling or resting during migration. When juveniles and adults migrated together in the same flock, the juvenile flew mostly behind the adult and was left behind when they separated. Juveniles showed greater improvement in flight efficiency throughout migration compared to adults which appears crucial because juveniles exhibiting higher flight costs suffered increased mortality. Our findings demonstrate the conflict between the juveniles' inferior flight skills and their urge to keep up with mixed adult-juvenile flocks. We suggest that increased flight costs are an important proximate cause of juvenile mortality in white storks and likely in other soaring migrants and that natural selection is operating on juvenile variation in flight efficiency.
Chronic stress induces anxiety disorders, whereas physical exercise is believed to help people with clinical anxiety. In the present study, we investigated the mechanisms underlying stress-induced anxiety and its counteraction by exercise using an established animal model of anxiety. Mice treated with restraint for 2 h daily for 14 days exhibited anxiety-like behaviors, including social and nonsocial behavioral symptoms, and these behavioral impairments lasted for more than 12 weeks after the stress treatment was removed. Despite these lasting behavioral changes, wheel-running exercise treatment for 1 h daily from post-stress days 1 - 21 counteracted anxiety-like behaviors, and these anxiolytic effects of exercise persisted for more than 2 months, suggesting that anxiolytic effects of exercise stably induced. Repeated restraint treatment up-regulated the expression of the neuropeptide, melanin-concentrating hormone (MCH), in the lateral hypothalamus, hippocampus, and basolateral amygdala, the brain regions important for emotional behaviors. In an in vitro study, treatment of HT22 hippocampal cells with glucocorticoid increased MCH expression, suggesting that MCH upregulation can be initially triggered by the stress hormone, corticosterone. In contrast, post-stress treatment with wheel-running exercise reduced the stress-induced increase in MCH expression to control levels in the lateral hypothalamus, hippocampus and basolateral amygdala. Administration of an MCH receptor antagonist (SNAP94847) to stress-treated mice was therapeutic against stress-induced anxiety-like behaviors. These results suggest that repeated stress produces long-lasting anxiety-like behaviors and upregulates MCH in the brain, while exercise counteracts stress-induced MCH expression and persisting anxiety-like behaviors. PMID:27574483
Lyons, Angela M; Thiele, Todd E
Neuropeptide Y (NPY) is a 36-amino-acid neuromodulator that is distributed throughout the central nervous system and has been implicated in a wide range of neurobiological responses including the integration of emotional behavior. The anxiolytic properties of NPY are modulated by NPY signaling in the hippocampus and in the central (CeA) and basolateral (BLA) nuclei of the amygdala. Recently, the neurotoxin saporin, when conjugated to NPY (NPY-SAP), was shown to selectively kill NPY receptor-expressing neurons and has been used as a tool to study the central NPY neurocircuitry involved with feeding behaviors. Here we determined if NPY-SAP can be used as a tool to study the central NPY neurocircuitry that modulates anxiety-like behaviors. BALB/cJ mice were given injection of either NPY-SAP or a control blank saporin (B-SAP) into the CeA or the basomedial hypothalamus (BMH) as a control injection site. The elevated zero maze test was used to assess anxiety-like behavior and NPY-SAP-induced lesions were verified using NPY Y1 receptor (Y1R) immunoreactivity (IR). Results showed that injection of NPY-SAP into the CeA site-specifically blunted Y1R IR in the CeA which was associated with a significant increase in anxiety-like behavior. Injection of NPY-SAP into the BMH, while locally blunting Y1R IR, promoted a compensatory increase of Y1R IR in the BLA and the CA3 region of the hippocampus which was associated with a significant reduction of anxiety-like behavior. The present set of experiments suggest that the NPY-SAP neurotoxin may be a useful tool for studying the NPY neurocircuitry that modulates anxiety-like behaviors.
Koltunowska, D; Gibula-Bruzda, E; Kotlinska, J H
Chronic amphetamine use results in anxiety-like states after drug cessation. The aim of the study was to determine a role of ionotropic and metabotropic glutamate receptor ligands in amphetamine-evoked withdrawal anxiety in the elevated plus-maze test in rats. In our study memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist did not reduce amphetamine withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate 5 receptor (mGluR5) antagonist) at the dose 200 and 400mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and a number of open arm entries. mGluR5 selective antagonist, MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine hydrochloride) and mGluR2/3 agonist, LY354740 (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid), caused effects similar to acamprosate at doses 1.25-5mg/kg and 2.5-5mg/kg, respectively. None of the glutamate ligands influenced locomotor activity of rats when given to the saline-treated group. Taking into account the positive correlation between amphetamine withdrawal-induced anxiety and relapse to amphetamine taking, our results suggest that modulation of mGluRs may prevent relapse to amphetamine and might pose a new direction in amphetamine abuse therapy.
Strekalova, Tatyana; Evans, Matthew; Costa-Nunes, Joao; Bachurin, Sergey; Yeritsyan, Naira; Couch, Yvonne; Steinbusch, Harry M W; Eleonore Köhler, S; Lesch, Klaus-Peter; Anthony, Daniel C
An association between metabolic abnormalities, hypercholesterolemia and affective disorders is now well recognized. Less well understood are the molecular mechanisms, both in brain and in the periphery, that underpin this phenomenon. In addition to hepatic lipid accumulation and inflammation, C57BL/6J mice fed a high-cholesterol diet (0.2%) to induce non-alcoholic fatty liver disease (NAFLD), exhibited behavioral despair, anxiogenic changes, and hyperlocomotion under bright light. These abnormalities were accompanied by increased expression of transcript and protein for Toll-like receptor 4, a pathogen-associated molecular pattern (PAMP) receptor, in the prefrontal cortex and the liver. The behavioral changes and Tlr4 expression were reversed ten days after discontinuation of the high-cholesterol diet. Remarkably, the dietary fat content and body mass of experimental mice were unchanged, suggesting a specific role for cholesterol in the molecular and behavioral changes. Expression of Sert and Cox1 were unaltered. Together, our study has demonstrated for the first time that high consumption of cholesterol results in depression- and anxiety-like changes in C57BL/6J mice and that these changes are unexpectedly associated with the increased expression of TLR4, which suggests that TLR4 may have a distinct role in the CNS unrelated to pathogen recognition.
Lee, Bombi; Sur, Bongjun; Cho, Seong-Guk; Yeom, Mijung; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun
Single prolonged stress (SPS), a rat model of post-traumatic stress disorder (PTSD), induces alterations in the hypothalamic-pituitary-adrenal axis. Korean red ginseng, whose major active component is ginsenoside Rb1 (GRb1), is one of the widely used traditional anxiolytics. However, the efficacy of GRb1 in alleviating PTSD-associated anxiety-like abnormalities has not been investigated. The present study used several behavioral tests to examine the effects of GRb1 on symptoms of anxiety in rats after SPS exposure and on the central noradrenergic system. Male Sprague-Dawley rats received GRb1 (10 or 30 mg/kg, i.p., once daily) during 14 days of SPS. Daily GRb1 (30 mg/kg) administration significantly increased the number and duration of open-arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, reduced grooming behaviors in the EPM test, and increased the total number of line crossings of an open field after SPS. The higher dose of GRb1 also blocked SPS-induced decreases in hypothalamic neuropeptide Y expression, increases in locus coeruleus tyrosine hydroxylase expression, and decreases in hippocampal mRNA expression of brain-derived neurotrophic factor. These findings suggest that GRb1 has anxiolytic-like effects on both behavioral and biochemical symptoms similar to those observed in patients with PTSD.
Li, Qian; Yue, Na; Liu, Shen-Bin; Wang, Zhi-Fu; Mi, Wen-Li; Jiang, Jian-Wei; Wu, Gen-Cheng; Yu, Jin; Wang, Yan-Qing
Growing evidence indicates that chronic neuropathic pain is frequently accompanied by an array of psychiatric diseases, such as depression and anxiety. Electroacupuncture (EA), as one therapy of traditional Chinese medicine, has displayed potent antidepressant-like effects in numerous clinical studies. The present study was designed to examine the possible effects of EA on the depressive and anxiety disorders induced by neuropathic pain. A classic rat model of neuropathic pain was produced by chronic constriction injury (CCI) of the sciatic nerve. EA was performed on acupoints "Bai-Hui" (GV20) and unilateral "Yang-Ling-Quan" (GB34). The antidepressive and anxiolytic effects of EA treatment were analyzed using the forced swimming test (FST) and the elevated plus maze (EPM) test, respectively. CCI resulted in remarkable depression- and anxiety-like behaviors, whereas the chronic EA treatment significantly improved the behavioral deficits of CCI rats. Moreover, the phosphorylation level of the NMDA receptor type 1 (NR1) subunit was decreased in the hippocampus of CCI rats. Intriguingly, continuous EA treatment effectively blocked this decrease in the levels of pNR1. These results suggested that EA has antidepressive and anxiolytic effects on rats with neuropathic pain and that this might be associated with restoring the phosphorylation of NR1 in the hippocampus.
Li, Qian; Yue, Na; Liu, Shen-Bin; Wang, Zhi-Fu; Mi, Wen-Li; Jiang, Jian-Wei; Wu, Gen-Cheng; Yu, Jin; Wang, Yan-Qing
Growing evidence indicates that chronic neuropathic pain is frequently accompanied by an array of psychiatric diseases, such as depression and anxiety. Electroacupuncture (EA), as one therapy of traditional Chinese medicine, has displayed potent antidepressant-like effects in numerous clinical studies. The present study was designed to examine the possible effects of EA on the depressive and anxiety disorders induced by neuropathic pain. A classic rat model of neuropathic pain was produced by chronic constriction injury (CCI) of the sciatic nerve. EA was performed on acupoints “Bai-Hui” (GV20) and unilateral “Yang-Ling-Quan” (GB34). The antidepressive and anxiolytic effects of EA treatment were analyzed using the forced swimming test (FST) and the elevated plus maze (EPM) test, respectively. CCI resulted in remarkable depression- and anxiety-like behaviors, whereas the chronic EA treatment significantly improved the behavioral deficits of CCI rats. Moreover, the phosphorylation level of the NMDA receptor type 1 (NR1) subunit was decreased in the hippocampus of CCI rats. Intriguingly, continuous EA treatment effectively blocked this decrease in the levels of pNR1. These results suggested that EA has antidepressive and anxiolytic effects on rats with neuropathic pain and that this might be associated with restoring the phosphorylation of NR1 in the hippocampus. PMID:24795763
Xu, Hui; Vadakkan, Kunjumon I.; Ren, Ming; Knifed, Eva; Shum, Fanny; Quan, Jessica; Zhang, Xue-Han; Zhuo, Min
GABAergic transmission in the amygdala modulates the expression of anxiety. Understanding the interplay between GABAergic transmission and excitatory circuits in the amygdala is, therefore, critical for understanding the neurobiological basis of anxiety. Here, we used a multi-disciplinary approach to demonstrate that GluR5-containing kainate receptors regulate local inhibitory circuits, modulate the excitatory transmission from the basolateral amygdala to the central amygdala, and control behavioral anxiety. Genetic deletion of GluR5 or local injection of a GluR5 antagonist into the basolateral amygdala increases anxiety-like behavior. Activation of GluR5 selectively depolarized inhibitory neurons, thereby increasing GABA release and contributing to tonic GABA current in the basolateral amygdala. The enhanced GABAergic transmission leads to reduced excitatory inputs in the central amygdala. Our results suggest that GluR5 is a key regulator of inhibitory circuits in the amygdala and highlight the potential use of GluR5-specific drugs in the treatment of pathological anxiety. PMID:17245443
Amore, M.; Bertelli, M.; Villani, D.; Tamborini, S.; Rossi, M.
Background: Aggressive behaviour represents a frequent symptom in people with intellectual disability (PWID). Despite uncertain evidence of effectiveness, the use of antipsychotics (APs) drugs to treat aggressive behaviour is very common. Antipsychotic medication of aggressivity in PWID has recently become one of the most debated issues in mental…
Weinman, B; Haydon, S; Sapan, J
A 31-year-old woman with mental retardation who demonstrated total food refusal as the symptom of a conversion disorder was successfully treated with behavioural management techniques. The treatment utilized a shaping paradigm combined with relaxation procedures. The results supported the hypothesis that conversion disorder symptoms are maintained through their consequences, and the efficacy of behavioural treatments for those disorders.
Adams, Dawn; Oliver, C.
Background: The latter stages of dementia in individuals with Down syndrome are well documented; however, earlier cognitive and behavioural changes have only recently been described. Holland et al. suggested such early signs of dementia in this population are behavioural and are similar to those seen in frontotemporal dementia, but there is, as…
Haessler, Frank; Glaser, Thomas; Beneke, Manfred; Pap, Akos F; Bodenschatz, Ralf; Reis, Olaf
We investigated the effects of zuclopenthixol on aggressive behaviour in patients with intellectual disabilities by randomly withdrawing it after a 6-week period of open treatment. Of the 49 patients responding to the treatment, 39 took part in a randomised withdrawal trial. The placebo subgroup (n=20) showed more aggressive behaviour as indicated by outcomes observed by external raters on the Modified Overt Aggression Scale than did the continuing subgroup (n=19). The results indicate that discontinuation of zuclopenthixolin this population leads to an increase in aggressive behaviour.
A Comparison of Adults with Intellectual Disabilities with and without ASD on Parallel Measures of Challenging Behaviour: The Behavior Problems Inventory-01 (BPI-01) and Autism Spectrum Disorders-Behavior Problems for Intellectually Disabled Adults (ASD-BPA)
Rojahn, Johannes; Wilkins, Jonathan; Matson, Johnny L.; Boisjoli, Jessica
Challenging behaviour may not be part of the diagnostic criteria for Autistic Disorder but they are frequently exhibited by children and adults with this condition. Levels of challenging behaviours are highest in individuals with an autism spectrum disorder (ASD) and co-occurring intellectual disability (ID). The sample for this study consisted of…
Kumar, Jaya; Hapidin, Hermizi; Get Bee, Yvonne-Tee; Ismail, Zalina
Withdrawal from long-term ethanol consumption results in overexcitation of glutamatergic neurotransmission in the amygdala, which induces an anxiety-like syndrome. Most alcoholics that suffer from such symptoms frequently depend on habitual drinking as self-medication to alleviate their symptoms. Metabotropic glutamate receptor subtype 5 (mGlu5) and protein kinase C (PKC) epsilon have been reported to mediate acute and chronic effects of ethanol. This study explores the changes in mGlu5 and PKC epsilon in the amygdala following acute administration of ethanol during ethanol withdrawal (EW) induced anxiety. Male Wistar rats were fed a modified liquid diet containing low-fat cow milk, sucrose, and maltodextrin, with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into EW, the rats were intraperitoneally injected with normal saline and ethanol (2.5 g/kg, 20% v/v), and exposed to open-field and elevated plus maze tests. Then, amygdala tissue was dissected from the rat brain for Western blot and gene expression studies. EW-induced anxiety was accompanied by a significant increase in mGlu5, total PKC epsilon, and phosphorylated PKC epsilon protein levels, and also of mRNA of mGlu5 (GRM5) in the amygdala. Acute administration of ethanol significantly attenuated EW-induced anxiety as well as an EW-induced increase in GRM5. The acute challenge of ethanol to EW rats had little effect on the phosphorylated and total protein levels of PKC epsilon in the amygdala. Our results demonstrate that amygdala PKC epsilon may not be directly involved in the development of anxiety following EW.
Umpierre, Anthony D; Remigio, Gregory J; Dahle, E Jill; Bradford, Kate; Alex, Anitha B; Smith, Misty D; West, Peter J; White, H Steve; Wilcox, Karen S
Viral infection of the CNS can result in encephalitis and acute seizures, increasing the risk for later-life epilepsy. We have previously characterized a novel animal model of temporal lobe epilepsy that recapitulates key sequela in the development of epilepsy following viral infection. C57BL/6J mice inoculated with the Daniel's strain of Theiler's Murine Encephalomyelitis Virus (TMEV; 3×10(5) PFU, i.c.) display acute limbic seizures that secondarily generalize. A majority of acutely seized animals develop spontaneous seizures weeks to months later. As part of our investigation, we sought to assess behavioral comorbidity following TMEV inoculation. Anxiety, depression, cognitive impairment, and certain psychoses are diagnosed in persons with epilepsy at rates far more frequent than in the general population. We used a battery of behavioral tests to assess anxiety, depression, cognitive impairment, and general health in acutely seized animals inoculated with TMEV and compared behavioral outcomes against age-matched controls receiving a sham injection. We determined that TMEV-seized animals are less likely to move through the exposed center of an open field and are less likely to enter into the lighted half of a light/dark box; both behaviors may be indicative of anxiety-like behavior. TMEV-seized animals also display early and persistent reductions in novel object exploration during novel object place tasks and do not improve in their ability to find a hidden escape platform in Morris water maze testing, indicative of impairment in episodic and spatial memory, respectively. Cresyl violet staining at 35 and 250 days after injection reveals bilateral reductions in hippocampal area, with extensive sclerosis of CA1 evident bilaterally along the rostral-caudal axis. Early and persistent behavioral changes in the TMEV model provide surrogate markers for assessing disease progression as well as endpoints in screening for the efficacy of novel compounds to manage both
Xu, Peng; Qiu, Yi; Zhang, Yizhi; Βai, Yanping; Xu, Pengfei; Liu, Yuan; Kim, Jee Hyun
Background: 4-Methylethcathinone is a drug that belongs to the second generation of synthetic cathinones, and recently it has been ranked among the most popular “legal highs”. Although it has similar in vitro neurochemical actions to other drugs such as cocaine, the behavioral effects of 4-methylethcathinone remain to be determined. Methods: The addictive potential and locomotor potentiation by 4-methylethcathinone were investigated in rats using the conditioned place preference and sensitization paradigm. Methamphetamine was used as a positive control. Because synthetic cathinones can have psychological effects, we also examined anxiety-like behavior using the elevated plus maze. Results: A conditioning dose of 10mg/kg 4-methylethcathinone was able to induce conditioned place preference and reinstatement (following 2 weeks of withdrawal). Acute or repeated injections of 4-methylethcathinone at 3 or 10mg/kg failed to alter locomotor activity. At 30mg/kg, however, acute 4-methylethcathinone increased locomotor activity compared with saline, while chronic 4-methylethcathinone induced a delayed and attenuated sensitization compared with methamphetamine. Additionally, repeated daily injections of 4-methylethcathinone (30mg/kg) reduced, whereas methamphetamine increased time spent by rats in the open arm of an elevated plus maze compared with saline injections. Interestingly, a 2-week withdrawal period following chronic injections of 4-methylethcathinone or methamphetamine increased time spent in the open arm in all rats. Conclusions: The rewarding properties of 4-methylethcathinone were found to be dissociated from its effects on locomotor activity. Additionally, chronic 4-methylethcathinone use may trigger abnormal anxious behaviors. These behavioral effects caused by 4-methylethcathinone appear to last even after a withdrawal period. PMID:26612552
Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni
Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.
Ricci, Lesley A; Morrison, Thomas R; Melloni, Richard H
From the U.S. to Europe and Australia anabolic steroid abuse remains high in the adolescent population. This is concerning given that anabolic steroid use is associated with a higher incidence of pathological anxiety that often appears during withdrawal from use. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that adolescent anabolic/androgenic steroid (AAS) exposure predisposes hamsters to heightened levels of anxiety during AAS withdrawal that is modulated by serotonin (5HT) neural signaling. In the first two sets of experiments, adolescent AAS-treated hamsters were tested for anxiety 21 days after the cessation of AAS administration (i.e., during AAS withdrawal) using the elevated plus maze (EPM), dark/light (DL), and seed finding (SF) tests and then examined for differences in 5HT afferent innervation to select areas of the brain important for anxiety. In the EPM and DL tests, adolescent AAS exposure leads to significant increases in anxiety-like response during AAS withdrawal. AAS-treated hamsters showed long-term reductions in 5HT innervation within several areas of the hamster brain implicated in anxiety, most notably the anterior hypothalamus and the central and medial amygdala. However, no differences in 5HT were found in other anxiety areas, e.g., frontal cortex and lateral septum. In the last experiment, adolescent AAS-treated hamsters were scored for anxiety on the 21st day of AAS withdrawal following the systemic administration of saline or one of three doses of fluoxetine, a selective serotonin reuptake inhibitor. Saline-treated hamsters showed high levels of AAS withdrawal-induced anxiety, while treatment with fluoxetine reduced AAS withdrawal-induced anxiety. These findings indicate that early AAS exposure has potent anxiogenic effects during AAS withdrawal that are modulated, in part, by 5HT signaling.
Fossat, Pascal; Bacqué-Cazenave, Julien; De Deurwaerdère, Philippe; Cattaert, Daniel; Delbecque, Jean-Paul
In the animal kingdom, biogenic amines are widespread modulators of the nervous system that frequently interact to control mood. Our previous investigations in crayfish (Procambarus clarkii) have established that stress induces changes in brain serotonin (5-HT) concentrations that are responsible for the appearance of anxiety-like behavior (ALB). Here, we further analyze the roles of 5-HT and another biogenic amine, dopamine (DA), on the crayfish response to stress. We show that the intensity of crayfish ALB depends on the intensity of stressful stimulation and is associated with increased concentrations of 5-HT in the brain. These 5-HT levels were significantly correlated, before, as well as after stress, with those of DA, which were approximately 3- to 5-times less abundant. However, whereas the degree of ALB was clearly correlated with brain 5-HT concentrations, it was not significantly correlated with DA. Moreover, in contrast to injections of 5-HT, DA injections were not able to elicit a stress response or ALB. In addition, 5-HT and DA levels were not modified by treatment with the anxiolytic chlordiazepoxide, confirming that suppression of ALB by this GABA-A receptor ligand acts downstream and is independent of changes in crayfish bioamine levels. Our study also provides evidence that the anxiogenic effect of 5-HT injections can be prevented by a preliminary injection of 5-HT antagonists. Altogether, our results emphasize that the rises in brain concentrations of 5-HT, but not DA, play a role in controlling the induction and the intensity of crayfish ALB.
Kallupi, Marsida; Vendruscolo, Leandro F; Carmichael, Casey Y; George, Olivier; Koob, George F; Gilpin, Nicholas W
Electrophysiological data suggest a dual role of Y2 receptors (Y2 Rs) as autoreceptors regulating neuropeptide Y release and heteroceptors regulating gamma-aminobutyric acid release in the central amygdala (CeA). Here, we report that neither systemic (JNJ-31020028) nor intra-CeA (BIIE0246) Y2 R antagonism altered operant alcohol responding by alcohol-dependent or non-dependent rats. Conversely, BIIE0246 in the CeA reduced anxiety-like behavior in alcohol-dependent and alcohol-naïve rats. The finding that Y2 R antagonism reduces anxiety-like behavior but not alcohol drinking suggests that these two effects may occur via different functions of the Y2 R (e.g. autoreceptor versus heteroceptor function).
Patki, Gaurav; Solanki, Naimesh; Atrooz, Fatin; Ansari, Amber; Allam, Farida; Jannise, Brittany; Maturi, Jaganmohan; Salim, Samina
Social defeat (SD) induced stress causes physiological and behavioral deficits in rodents, including depression and anxiety-like behaviors, as well as memory impairment. Anxiolytic and mood elevating effects of physical exercise are also known. However, rescue effect of physical exercise in social defeat-induced anxiety, depression or memory impairment has not been addressed. The role of epigenetic mechanisms that potentially contribute to these rescue or protective effects is also not known. The present study investigated the effect of moderate treadmill exercise on anxiety-like behavior and memory function in rats subjected to SD using a modified version of the resident-intruder model for social stress (defeat). Changes in histone acetylation and histone-modifying enzymes were examined in hippocampus, amygdala and frontal cortex which are considered critical for anxiety, depression and cognition. Sprague Dawley rats were randomly assigned in four groups; control, exercised, social defeat, social defeat and exercise. At the end of the SD or control exposure lasting 30 min daily for 7 days, one group of SD rats was subjected to treadmill exercise for 2 weeks, whereas the other SD group was handled without exercise. Anxiety-like behavior tests and radial arm water maze test suggested that moderate treadmill exercise rescued social defeat induced anxiety-like behavior and memory impairment. Moreover, exercise normalized SD-induced increase in oxidative stress, most likely by adjusting antioxidant response. Our data suggests involvement of epigenetic mechanisms including histone acetylation of H3 and modulation of methyl-CpG-binding in the hippocampus that might contribute to the rescue effects of exercise in SD-induced behavioral deficits in rats.
Aujla, Harinder; Nedjadrasul, Daniel
Alcohol withdrawal is associated with neuroadaptation of stress-regulatory systems, including transmission of neuropeptides that have been implicated in anxiety-like performance. Nociceptin/Orphanin FQ (N/OFQ), an endogenous neuropeptide ligand at the NOP receptor, has been implicated in stress and has previously been shown to attenuate or exacerbate anxiety-like performance in rats following a biphasic dose response function. In addition, divergent actions on anxiety-like performance have been observed in alcohol-withdrawn vs. control animals, suggesting alcohol-induced alteration of N/OFQ transmission. In order to differentiate between whether this divergence resulted from a "switch" in the actions of N/OFQ vs. increased sensitivity in N/OFQ transmission, we assessed the actions of low doses of N/OFQ (0, 0.125, 0.25, or 0.5 μg) on two tests of anxiety, the shock-probe defensive burying and elevated plus maze tests, three weeks after the termination of a six-day regimen of alcohol or vehicle administration via intragastric intubation. Consistent with increased sensitivity in N/OFQ resulting from a history of alcohol intake, administration of a low dose of N/OFQ (0.25 μg) selectively attenuated anxiety-like behaviors in animals with a history of alcohol intake while controls did not exhibit any changes in performance. The present results suggest that withdrawal from alcohol produces an enduring increase in sensitivity in N/OFQ transmission - a finding that is consistent with previous studies demonstrating altered transmission in related neuropeptide systems.
Groves, Natalie J.; Bradford, DanaKai; Sullivan, Robert K. P.; Conn, Kyna-Anne; Aljelaify, Rasha Fahad; McGrath, John J.; Burne, Thomas H. J.
Epidemiological studies have shown that up to one third of adults have insufficient levels of vitamin D and there is an association between low vitamin D concentrations and adverse brain outcomes, such as depression. Vitamin D has been shown to be involved in processes associated with neurogenesis during development. Therefore, the aim of this study was to test the hypothesis that adult vitamin D (AVD) deficiency in BALB/c mice was associated with (a) adult hippocampal neurogenesis at baseline, b) following 6 weeks of voluntary wheel running and (c) a depressive-like phenotype on the forced swim test (FST), which may be linked to alterations in hippocampal neurogenesis. We assessed proliferation and survival of adult born hippocampal neurons by counting the number of cells positive for Ki67 and doublecortin (DCX), and incorporation of 5-Bromo-2’-Deoxyuridine (BrdU) within newly born mature neurons using immunohistochemistry. There were no significant effects of diet on number of Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly increased number of Ki67+ cells and BrdU incorporation, and decreased immobility time in the FST, after voluntary wheel running. A significant correlation was found in control mice between immobility time in the FST and level of hippocampal neurogenesis, however, no such correlation was found for AVD-deficient mice. We conclude that AVD deficiency was not associated with impaired proliferation or survival of adult born neurons in BALB/c mice and that the impact on rodent behaviour may not be due to altered neurogenesis per se, but to altered function of new hippocampal neurons or processes independent of adult neurogenesis. PMID:27043014
Groves, Natalie J; Bradford, DanaKai; Sullivan, Robert K P; Conn, Kyna-Anne; Aljelaify, Rasha Fahad; McGrath, John J; Burne, Thomas H J
Epidemiological studies have shown that up to one third of adults have insufficient levels of vitamin D and there is an association between low vitamin D concentrations and adverse brain outcomes, such as depression. Vitamin D has been shown to be involved in processes associated with neurogenesis during development. Therefore, the aim of this study was to test the hypothesis that adult vitamin D (AVD) deficiency in BALB/c mice was associated with (a) adult hippocampal neurogenesis at baseline, b) following 6 weeks of voluntary wheel running and (c) a depressive-like phenotype on the forced swim test (FST), which may be linked to alterations in hippocampal neurogenesis. We assessed proliferation and survival of adult born hippocampal neurons by counting the number of cells positive for Ki67 and doublecortin (DCX), and incorporation of 5-Bromo-2'-Deoxyuridine (BrdU) within newly born mature neurons using immunohistochemistry. There were no significant effects of diet on number of Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly increased number of Ki67+ cells and BrdU incorporation, and decreased immobility time in the FST, after voluntary wheel running. A significant correlation was found in control mice between immobility time in the FST and level of hippocampal neurogenesis, however, no such correlation was found for AVD-deficient mice. We conclude that AVD deficiency was not associated with impaired proliferation or survival of adult born neurons in BALB/c mice and that the impact on rodent behaviour may not be due to altered neurogenesis per se, but to altered function of new hippocampal neurons or processes independent of adult neurogenesis.
Kinsey, Steven G; Bailey, Michael T; Sheridan, John F; Padgett, David A; Avitsur, Ronit
The experimental model, social disruption (SDR), is a model of social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because social defeat has been reported to cause anxiety- and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxiety- and depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least 1 week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that social disruption stress causes an increase in anxiety-like behaviors, but not depressive-like behaviors.
Fan, Junming; Fan, Xiaofang; Li, Yang; Guo, Jinbin; Xia, Dongmei; Ding, Lu; Zheng, Qingqing; Wang, Wei; Xue, Feng; Chen, Ran; Liu, Shouting; Hu, Lianggang; Gong, Yongsheng
This study aims to investigate whether inflammation mediated by NF-κB activation is involved in the induction of anxiety-like behavior in chronic normobaric hypoxia (CNH) exposed rats and to investigate the underlying mechanism. To this end, rats were exposed in a normobaric hypoxic chamber with a fraction of inspired oxygen (FIO2) of ∼ 10%, 23 h/d, continues for 2 weeks. Anxiety-like behavior was tested by elevated plus maze and open field, inflammatory response, nucleus translocation of NF-κB, and signaling pathway in hippocampus were examined. CNH induced a significant increase of anxiety- like behavior and inflammation responses, which were ameliorated by NF-κB inhibitor, PDTC pretreatment, suggesting that the anxiogenic effect induced by inflammation is through NF-κB activation. CNH treatment significantly increased nucleus translocation of p65 and p105 in hippocampus, which was suppressed by PDTC pretreatment. In addition, CNH treatment significantly increased Iba-1, iNOS, COX-2, and p-PKA in hippocampus, which were blocked by PDTC pretreatment, suggesting CNH may activate microglia cells in hippocampus through NF-κB pathway. In conclusion, our results illustrate a mechanism that, activation of NF-κB in hippocampus may trigger the proinflammatory response of microglia cells, and iNOS-PKA pathway may involve in anxiogenic effect in CNH exposed rats.
Kinsey, Steven G.; Bailey, Michael T.; Sheridan, John F.; Padgett, David A.; Avitsur, Ronit
The experimental model, social disruption (SDR), is a model of social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because social defeat has been reported to cause anxiety- and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxiety- and depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least one week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that social disruption stress causes an increase in anxiety-like behaviors, but not depressive-like behaviors. PMID:17178210
Investigated the behaviors for processing language input demonstrated by five adults beginning to learn Hindi as a second language through the Total Physical Response method. The study suggests that, when adult learners are provided with comprehensive input, they engage in a variety of behaviors to extract meaning from it. (73 references) (GLR)
Walf, Alicia A; Paris, Jason J; Frye, Cheryl A
Decline in the ovarian steroid, estradiol (E(2)), with the menopause transition may influence cognitive and affective processing of older women and there is evidence that hormone replacement therapies (HRTs) with E(2)-mimetics may provide benefit in some, but not all, women. The parameters that play a role in determining whether the response to HRTs is positive are of interest. It may be that the likelihood for positive responses is related to the timing of E(2)-replacement following E(2) decline. As such, in the present study an animal model was utilized to investigate this. We investigated the effects of long- versus short-term E(2)-replacement by examining cognitive (object placement task), anxiety (open field, mirror maze, light-dark transition task), and depression (forced swim task) behavior of female rats that were ovariectomized (OVX) at middle-age (14 months) or older (19 months) and implanted with E(2)-filled implants at the time of surgery or after a delay of 5 months, or OVX at 14 months of age and never replaced with E(2). Rats were tested at 20 months of age. The hypothesis that was tested was that rats would have reduced anxiety and depression behavior and improved cognitive performance with E(2)-replacement at ovarian cessation, compared to a delay in E(2)-replacement. Performance in the object placement task was improved in rats that were OVX and then received continuous E(2)-replacement, compared to those that were OVX and continuously administered placebo vehicle. In the open field and forced swim task, there was an increase in anti-anxiety and anti-depression behavior, respectively, among rats that were OVX and then received continuous E(2)-replacement, compared to OVX rats administered vehicle or those that experienced a delay in E(2)-replacement. In the mirror maze and light-dark transition task, E(2)-replacement at OVX, or after a delay, reduced anxiety-like behavior. Thus, E(2)-replacement reduced anxiety and depression behavior and improved
Gormez, A; Rana, F; Varghese, S
We aimed to determine clinical effectiveness of pharmacological interventions for self-injurious behaviour in adults with intellectual disability. We searched the following databases: CENTRAL; MEDLINE; EMBASE; PsycINFO; CINAHL; SCI; SSCI; Conference Proceedings Citation Index - Science; Conference Proceedings Citation Index - Social Science and Humanities; ZETOC; World Cat .We also searched ClinicalTrials.gov,ICTRP and the reference lists of included trials. We included randomised controlled trials that examined drug interventions versus placebo for self-injurious behaviour. We found five double-blind, placebo-controlled trials, which included a total of 50 people. Four trials compared the effects of naltrexone versus placebo and one trial clomipramine versus placebo. We did not identify any relevant placebo-controlled trials for other drugs. We presented a narrative summary, as meta-analysis was not appropriate due to differences in study designs, differences between interventions and heterogeneous outcome measures. There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating self-injurious behaviour. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo.
Van den Berg, C L; Van Ree, J M; Spruijt, B M; Kitchen, I
The consequences of juvenile isolation and morphine treatment during the isolation period on (social) behaviour and mu-, delta- and kappa-opioid receptors in adulthood were investigated by using a social interaction test and in vitro autoradiography in rats. Juvenile isolation reduced social exploration in adults. Morphine treatment counteracted this reduction in isolated rats, but decreased social exploration in nonisolated rats. Self-grooming and nonsocial exploration were enhanced after juvenile isolation. Morphine treatment had no effect on self-grooming, but suppressed nonsocial exploration in isolated rats. With respect to the opioid receptors, juvenile isolation resulted in regiospecific increases in mu-binding sites with a 58% increase in the basolateral amygdala and a 33% increase in the bed nucleus of stria terminalis. Morphine treatment in isolated rats reversed this upregulation in both areas. The number of delta-binding sites did not differ between the experimental groups. A general upregulation of kappa-binding sites was observed after juvenile isolation, predominantly in the cortical regions, the hippocampus and the substantia nigra. Morphine treatment did not affect the upregulation of kappa-receptors. The results show that juvenile isolation during the play period causes long-term effects on social and nonsocial behaviours and on the number of mu- and kappa- but not delta-opioid receptors in distinct brain areas. The number of mu-receptors in the basolateral amygdala appears to be negatively correlated with the amount of social exploration in adult rats.
Moodie, Crawford; Hastings, Gerard; Joossens, Luk
Plain (unbranded) packaging for cigarettes is at the top of the tobacco control agenda in both Australia and Europe. The evidence suggests that it will benefit public health by decreasing the appeal of tobacco products and increasing the power of the health warning. The tobacco industry instead argues that plain packaging would make it easier to counterfeit cigarettes, which would both confuse consumers and reduce price; thereby increasing consumption. Using focus group research we examined young adult smokers (N = 54) perceptions of, and ability to recognize, illicit tobacco and the possible impact of plain packaging on illicit tobacco purchasing behaviour. We found that the pack has no impact on the decision to buy illicit tobacco. Smokers were easily able to identify counterfeit cigarettes, not least by the pack, and buy it knowingly and in the full expectation that it will be inferior in quality. Illicit tobacco purchase, including that for counterfeit tobacco, was instead driven by availability and price. Given the extremely low manufacturing cost, per pack, of certain types of illicit cigarettes, it is difficult to envisage how plain packaging would alter the price of illicit tobacco in any meaningful way. The findings therefore suggest that a move to plain packaging would have no impact on young adult smokers' purchase behaviour.
Hassiotis, Angela; Parkes, Charles; Jones, Lee; Fitzgerald, Brian; Romeo, Renee
Background: English policy argues that people with intellectual disabilities should be supported in their local communities. There is considerable evidence that this aspiration is not being achieved. This paper seeks to look at the subsection of people with intellectual disabilities who have expensive care needs because of challenging behaviour,…
Castilla, J; Barrio, G; Belza, M J; de la Fuente, L
To study the association of the consumption of alcohol and other psychoactive drugs with sexual risk behaviour for HIV infection, data from a representative sample of the Spanish population aged 18-39 years were analysed. A national household survey was carried out in 1996 using a combination of face-to-face interviews and self-administered questionnaires. The survey included 5253 subjects aged 18-39 years who provided information on alcohol and drug consumption, number of sexual partners and condom use with the steady partner and with casual partners in the 12 months before the survey. Of those surveyed, 27.4% had been drunk at least once and 20.5% had consumed drugs. Both behaviours were associated with male sex, younger age, higher educational level, being single and having had more than one sexual partner. In the logistic regression analysis adjusting for the sociodemographic variables, the greater frequency of drunkenness and cannabis use were associated with having more than one sexual partner. Regular condom use was significantly less frequent among cocaine users and more frequent among opiate users, but was not associated with the use of other drugs. Sexual risk behaviour (i.e. more than one partner and failure to use a condom regularly) was more frequent among persons who had been drunk or used cannabis or cocaine. Excessive consumption of alcohol, and cannabis and cocaine use are independently associated with sexual behaviour involving greater risk of HIV infection or transmission.
Ruedrich, S. L.; Swales, T. P.; Rossvanes, C.; Diana, L.; Arkadiev, V.; Lim, K.
Objective: Atypical antipsychotic medications have largely supplanted their typical counterparts, both for psychosis and for the treatment of aggression and/or self-injurious behaviour (SIB), in persons with intellectual disabilities (ID). However, with the exception of risperidone, little systematic research supports their use in such persons.…
Crocker, A. G.; Mercier, C.; Allaire, J.-F.; Roy, M.-E.
Background: Despite the heterogeneity in aggressive behaviours observed among individuals with intellectual disabilities (ID), little attention has been paid to the identification of typologies of aggression among individuals with mild or moderate ID and their associated factors. Objective: The goal of the present study was to identify profiles of…
Gagliardi, C.; Martelli, S.; Tavano, A.; Borgatti, R.
Background: The increased interest in social interaction in Williams-Beuren syndrome (WBS) is evident from infancy onwards, together not only with increased empathy, positive interpersonal bias, but also with social disinhibition. Previous studies have described behavioural and emotional problems as being widely represented in WBS. There is…
Cooper, S.-A.; Smiley, E.; Allan, L. M.; Jackson, A.; Finlayson, J.; Mantry, D.; Morrison, J.
Background: Self-injurious behaviour (SIB) is a serious condition, with implications for the person, their family and financial costs to the state providing care. The previously reported prevalence of SIB has ranged from 1.7% to 41%, or 1.7%-23.7% in community studies. There has been little study of remission rate, and incidence has not previously…
Murphy, G. H.; O'Callaghan, A. C.; Clare, I. C. H.
Background: People with intellectual disabilities (ID) are particularly vulnerable to abuse, and most incidents come to light through victim disclosure. Those people with severe or profound ID are not able to describe what has happened to them. This project aimed to describe the consequences of abuse and changes in behaviour following alleged…
Kishita, Naoko; Laidlaw, Ken
The current meta-analysis compared the efficacy of CBT for GAD between adults of working age and older people. In addition, we conducted a qualitative content analysis of treatment protocols used in studies with older clients to explore potential factors that may enhance treatment outcomes with this particular client group. Applying the inclusion criteria resulted in the identification of 15 studies with 22 comparisons between CBT and control groups (770 patients). When examining overall effect sizes for CBT for GAD between older people and adults of working age there were no statistically significant differences in outcome. However, overall effect size of CBT for GAD was moderate for older people (g=0.55, 95% CI 0.22-0.88) and large for adults of working age (g=0.94, 95% CI 0.52-1.36), suggesting that there is still room for improvement in CBT with older people. The main difference in outcome between CBT for GAD between the two age groups was related to methodological quality in that no older people studies used an intention-to-treat design. The content analysis demonstrated that studies with older clients were conducted according to robust CBT protocols but did not take account of gerontological evidence to make them more age-appropriate.
Mukama, Trasias; Ndejjo, Rawlance; Musinguzi, Geofrey; Musoke, David
Introduction Medical male circumcision is currently recognized as an additional important HIV preventive intervention to reduce the risk of heterosexually acquired HIV infection in men. However, sexual behaviours after medical circumcision can potentially reduce the expected benefits of the practice. This study explored the perceptions about medical male circumcision and sexual behaviours of adults in Kayunga district, Uganda. Methods A cross-sectional study was carried out among 393 respondents using a semi structured questionnaire. In addition, four focus group discussions were conducted. Quantitative data was analysed using STATA 12. Univariate, bivariate and multivariate analyses were carried out. Qualitative data was analysed thematically. Results The study established various perceptions about medical male circumcision and sexual behaviours. Majority 247 (64.5%) did not perceive circumcision as a practice that can lead men to have multiple sexual partners. Males were 3 times more likely to think that circumcision would lead to having multiple sexual partners than females (AOR=2.99, CI: 1.93-4.61). Only 89 (23.2%) believed that circumcision would lead to complacency and compromise the use of condoms to prevent against infection with HIV. Respondents who had education above primary were less likely to think that circumcision would compromise the use of condoms (AOR=0.49, CI: 0.31- 0.79). The perception that circumcised youths were less likely to abstain from sexual intercourse was less held among those with education above primary (AOR=0.58, CI: 0.37-0.91) and those older than 30 years (AOR=0.59, CI: 0.38-0.92). Conclusion There were gaps in knowledge and negative perceptions about MMC in the study community. Measures are needed to avert the negative perceptions by equipping communities with sufficient, accurate and consistent information about medical male circumcision and sexual behaviour. PMID:26985272
Christopher, Rose; Horsley, Sarah
The Dudley Behavioural Support Team (BST) was set up based on Positive Behavioural Support (PBS) principles to support individuals with behaviours that challenge. The Winterbourne Review emphasises the importance of developing high-quality specialist community services and the Ensuring Quality Services (Local Government Association & NHS…
O'Connor, Kieron P; Lavoie, Marc E; Stip, Emmanuel; Borgeat, François; Laverdure, Anick
The first aim of the present study was to compare performance of people with tic disorders (TD) and controls on executive function and a range of skilled motor tests requiring complex performance, guided movements, hand co-ordination, and fine control of steadiness. The second aim was to investigate the effect of cognitive behaviour therapy (CBT) on motor performance. A total of 55 patients with TD were recruited at baseline from participants in a behavioural management programme. A comparison group of 55 patients suffering from a variety of habit disorders (HD) involving complex manual movements, were matched on age and level of education to 34 non-psychiatric controls. Participants were evaluated pre- and post-treatment and post-waitlist with a neuropsychological evaluation focusing on executive function (Wisconsin Card Sorting Test, WCST) and skilled motor performance (Purdue Pegboard, Hole Steadiness Test, and the Groove Test). Results revealed WCST scores in the normal range, while motor performance differed significantly on the Purdue Pegboard Tests in both TD and HD as compared to the control group. Cognitive-behavioural treatment selectively improved motor performance in both clinical groups compared to waitlist control, and this improvement related to clinical outcome measures.
Cuomo, V; Cagiano, R; Coen, E; Mocchetti, I; Cattabeni, F; Racagni, G
Rats were administered 0.5 mg/kg SC of haloperidol (H) or saline (S) daily from day 1 after birth until 20 days of age. At 60 days of age (40 days after the postnatal treatment with H or S was interrupted) the stereotyped behaviour and the effects on locomotor activity elicited by apomorphine in S- and H-pretreated rats were investigated. The intensity of apomorphine (0.5--1 mg/kg, SC)-induced stereotyped behaviour was significantly greater in the H-pretreated group than in S-pretreated animals and this was accompanied by a much more marked reduction of locomotor activity in H-pretreated than in S-pretreated rats. Finally, at 80 days of age (60 days after the postnatal treatment with H or S was interrupted) rats were subjected to a Differential Reinforcement of Low Rates schedule (DRL 15-s). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid on S-pretreated rats than in H-pretreated ones. In parallel biochemical experiments, acute H produced smaller increases in dopamine turnover in chronic H-treated rats compared with S-treated controls. These data indicate that H treatment in neonatal rats induces behavioural and biochemical changes which can be observed up to 60 days after H withdrawal.
Greve, Christian; Zijlstra, Wiebren; Hortobágyi, Tibor; Bongers, Raoul M
Sit-to-stand is a fundamental activity of daily living, which becomes increasingly difficult with advancing age. Due to severe loss of leg strength old adults are required to change the way they rise from a chair and maintain stability. Here we examine whether old compared to young adults differently prioritize task-important performance variables and whether there are age-related differences in the use of available motor flexibility. We applied the uncontrolled manifold analysis to decompose trial-to-trial variability in joint kinematics into variability that stabilizes and destabilizes task-important performance variables. Comparing the amount of variability stabilizing and destabilizing task-important variables enabled us to identify the variable of primary importance for the task. We measured maximal isometric voluntary force of three muscle groups in the right leg. Independent of age and muscle strength, old and young adults similarly prioritized stability of the ground reaction force vector during sit-to-stand. Old compared to young adults employed greater motor flexibility, stabilizing ground reaction forces during sit-to-sand. We concluded that freeing those degrees of freedom that stabilize task-important variables is a strategy used by the aging neuromuscular system to compensate for strength deficits.
Golovatch, Yelena; Vanderplank, Robert
This article reports on an investigation into the attributions of success and perceived areas of strength and weakness of adult learners of English as a foreign language in the Department of Continuing Education at Minsk State Linguistic University, Belarus. The students attributed their limited progress in learning the foreign language mainly to…
Fisette, Alexandre; Fernandes, Maria F.; Hryhorczuk, Cécile; Poitout, Vincent; Alquier, Thierry; Fulton, Stephanie
Background: GPR120 (FFAR4) is a G-protein coupled receptor implicated in the development of obesity and the antiinflammatory and insulin-sensitizing effects of omega-3 (ω-3) polyunsaturated fatty acids. Increasing central ω-3 polyunsaturated fatty acid levels has been shown to have both anorectic and anxiolytic actions. Despite the strong clinical interest in GPR120, its role in the brain is largely unknown, and thus we sought to determine the impact of central GPR120 pharmacological activation on energy balance, food reward, and anxiety-like behavior. Methods: Male C57Bl/6 mice with intracerebroventricular cannulae received a single injection (0.1 or 1 µM) or continuous 2-week infusion (1 µM/d; mini-pump) of a GPR120 agonist or vehicle. Free-feeding intake, operant lever-pressing for palatable food, energy expenditure (indirect calorimetry), and body weight were measured. GPR120 mRNA expression was measured in pertinent brain areas. Anxiety-like behavior was assessed in the elevated-plus maze and open field test. Results: GPR120 agonist injections substantially reduced chow intake during 4 hours postinjection, suppressed the rewarding effects of high-fat/-sugar food, and blunted approach-avoidance behavior in the open field. Conversely, prolonged central GPR120 agonist infusions reduced anxiety-like behavior in the elevated-plus maze and open field, yet failed to affect free-feeding intake, energy expenditure, and body weight on a high-fat diet. Conclusion: Acute reductions in food intake and food reward suggest that GPR120 could mediate the effects of central ω-3 polyunsaturated fatty acids to inhibit appetite. The anxiolytic effect elicited by GPR120 agonist infusions favors the testing of compounds that can enter the brain to activate GPR120 for the mitigation of anxiety. PMID:26888796
Gupta, Deepali; Radhakrishnan, Mahesh; Kurhe, Yeshwant
Increased prevalence and high comorbidity of depression-like mood disorders and diabetes have prompted investigation of new targets and potential contributing agents. There is considerable evidence supporting the inconsistent clinical efficacy and persistent undesirable effects of existing antidepressant therapy for depression associated with diabetes. Therefore, the present study was aimed at investigating the effect of ondansetron, a selective 5HT3 receptor antagonist in attenuating depression and anxiety-like behavior comorbid with diabetes. Experimentally, Swiss albino mice were rendered diabetic by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200 mg/kg). After 8 weeks, diabetic mice received a single dose of vehicle/ondansetron (0.5 and 1 mg/kg, p.o.)/fluoxetine (the positive control, 10 mg/kg p.o.) for 28 days. Thereafter, behavioral studies were conducted to test depression-like behavior using forced swim test (FST) and anxiety-like deficits using hole-board and light-dark tests, followed by biochemical estimation of serotonin content in discrete brain regions. The results demonstrated that, STZ-induced diabetic mice exhibited increased duration of immobility and decreased swimming behavior in FST, reduced exploratory behavior during hole-board test and increased aversion to brightly illuminated light area in light-dark test as compared to non-diabetic mice, while ondansetron (similar to fluoxetine) treatment significantly reversed the same. Biochemical assay revealed that ondansetron administration attenuated diabetes-induced neurochemical impairment of serotonin function, indicated by elevated serotonin levels in discrete brain regions of diabetic mice. Collectively, the data indicate that ondansetron may reverse depression and anxiety-like behavioral deficits associated with diabetes in mice and modulation of serotonergic activity may be a key mechanism of the compound.
de Noronha, Sylvana Rendeiro; Campos, Glenda Viggiano; Abreu, Aline Rezende; de Souza, Aline Arlindo; Chianca, Deoclécio A; de Menezes, Rodrigo C
Overweight and obesity are conditions associated with an overall range of clinical health consequences, and they could be involved with the development of neuropsychiatric diseases, such as generalized anxiety disorder (GAD) and panic disorder (PD). A crucial brain nuclei involved on the physiological functions and behavioral responses, especially fear, anxiety and panic, is the dorsomedial hypothalamus (DMH). However, the mechanisms underlying the process whereby the DMH is involved in behavioral changes in obese rats still remains unclear. The current study further investigates the relation between obesity and generalized anxiety, by investigating the GABAA sensitivity to pharmacological manipulation within the DMH in obese rats during anxiety conditions. Male Wistar rats were divided in two experimental groups: the first was fed a control diet (CD; 11% w/w) and second was fed a high fat diet (HFD; 45% w/w). Animals were randomly treated with muscimol, a GABAA agonist and bicuculline methiodide (BMI), a GABAA antagonist. Inhibitory avoidance and escape behaviors were investigated using the Elevated T-Maze (ETM) apparatus. Our results revealed that the obesity facilitated inhibitory avoidance acquisition, suggesting a positive relation between obesity and the development of an anxiety-like state. The injection of muscimol (an anxiolytic drug), within the DMH, increased the inhibitory avoidance latency in obese animals (featuring an anxiogenic state). Besides, muscimol prolonged the escape latency and controlling the possible panic-like behavior in these animals. Injection of BMI into the DMH was ineffective to produce an anxiety-like effect in obese animals opposing the results observed in lean animals. These findings support the hypotheses that obese animals are susceptible to develop anxiety-like behaviors, probably through changes in the GABAergic neurotransmission within the DMH.
Tarr, Andrew J; Galley, Jeffrey D; Fisher, Sydney E; Chichlowski, Maciej; Berg, Brian M; Bailey, Michael T
There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS), and studies demonstrate that stressor exposure significantly alters gut microbiota community structure. We tested whether oligosaccharides naturally found in high levels in human milk, which have been reported to impact brain development and enhance the growth of beneficial commensal microbes, would prevent stressor-induced alterations in gut microbial community composition and attenuate stressor-induced anxiety-like behavior. Mice were fed standard laboratory diet, or laboratory diet containing the human milk oligosaccharides 3'Sialyllactose (3'SL) or 6'Sialyllactose (6'SL) for 2 weeks prior to being exposed to either a social disruption stressor or a non-stressed control condition. Stressor exposure significantly changed the structure of the colonic mucosa-associated microbiota in control mice, as indicated by changes in beta diversity. The stressor resulted in anxiety-like behavior in both the light/dark preference and open field tests in control mice. This effect was associated with a reduction in immature neurons in the dentate gyrus as indicated by doublecortin (DCX) immunostaining. These effects were not evident in mice fed milk oligosaccharides; stressor exposure did not significantly change microbial community structure in mice fed 3'SL or 6'SL. In addition, 3'SL and 6'SL helped maintain normal behavior on tests of anxiety-like behavior and normal numbers of DCX+ immature neurons. These studies indicate that milk oligosaccharides support normal microbial communities and behavioral responses during stressor exposure, potentially through effects on the gut microbiota-brain axis.
Hackler, Elizabeth A; Turner, Greg H; Gresch, Paul J; Sengupta, Saikat; Deutch, Ariel Y; Avison, Malcolm J; Gore, John C; Sanders-Bush, Elaine
Activation of 5-hydroxytryptamine2C (5-HT(2C)) receptors by the 5-HT(2) receptor agonist m-chlorophenylpiperazine (m-CPP) elicits anxiety in humans and anxiety-like behavior in animals. We compared the effects of m-CPP with the anxiogenic GABA(A) receptor inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) on both anxiety-like behavior and regional brain activation using functional magnetic resonance imaging (fMRI) in the rat. We also determined whether the selective 5-HT(2C) receptor antagonist SB 242084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] would blunt m-CPP or FG-7142-induced neuronal activation. Both m-CPP (3 mg/kg i.p.) and FG-7142 (10 mg/kg i.p.) elicited anxiety-like behavior when measured in the social interaction test, and pretreatment with SB 242084 (1 mg/kg i.p.) completely blocked the behavioral effects of both anxiogenic drugs. Regional brain activation in vivo in response to anxiogenic drug challenge was determined by blood oxygen level-dependent (BOLD) fMRI using a powerful 9.4T magnet. Region of interest analyses revealed that m-CPP and FG-7142 significantly increased BOLD signals in brain regions that have been linked to anxiety, including the amygdala, dorsal hippocampus, and medial hypothalamus. These BOLD signal increases were blocked by pretreatment with SB 242084. In contrast, injection of m-CPP and FG-7142 resulted in BOLD signal decreases in the medial prefrontal cortex that were not blocked by SB 242084. In conclusion, the brain activation signals produced by anxiogenic doses of both m-CPP and FG-7142 are mediated at least partially by the 5-HT(2C) receptor, indicating that this receptor is a key component in anxiogenic neural circuitry.
Rostami, Amin; Shahani, Minoo; Zarrindast, Mohammad Reza; Semnanian, Saeed; Rahmati Roudsari, Mohammad; Rezaei Tavirani, Mostafa; Hasanzadeh, Hadi
Introduction: The effects of electromagnetic fields on biological organisms have been a controversial and also interesting debate over the past few decades, despite the wide range of investigations, many aspects of extremely low frequency electromagnetic fields (ELF/EMFs) effects including mechanism of their interaction with live organisms and also their possible biological applications still remain ambiguous. In the present study, we investigated whether the exposures of ELF/EMF with frequencies of 3 Hz and 60 Hz can affect the memory, anxiety like behaviors, electrophysiological properties and brain’s proteome in rats. Methods: Male rats were exposed to 3 Hz and 60 Hz ELF/EMFs in a protocol consisting of 2 cycles of 2 h/day exposure for 4 days separated with a 2-day interval. Short term memory and anxiety like behaviors were assessed immediately, 1 and 2 weeks after the exposures. Effects of short term exposure were also assessed using electrophysiological approach immediately after 2 hours exposure. Results: Behavioral test revealed that immediately after the end of exposures, locomotor activity of both 3 Hz and 60 Hz exposed groups significantly decreased compared to sham group. This exposure protocol had no effect on anxiety like behavior during the 2 weeks after the treatment and also on short term memory. A significant reduction in firing rate of locus coeruleus (LC) was found after 2 hours of both 3 Hz and 60 Hz exposures. Proteome analysis also revealed global changes in whole brain proteome after treatment. Conclusion: Here, some evidence regarding the fact that such exposures can alter locomotor activity and neurons firing rate in male rats were presented. PMID:27330708
Farajdokht, Fereshteh; Babri, Shirin; Karimi, Pouran; Alipour, Mohammad Reza; Bughchechi, Ramin; Mohaddes, Gisou
Chronic migraine is a debilitating disorder that has a significant impact on patients and society. Nearly all migraineurs frequently reported light sensitivity during a headache attack. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the activation of trigeminal system and migraine pain. To identify the effect of chronic ghrelin treatment on endogenous PACAP and associated symptoms of migraine, an experimental chronic migraine model was induced by intermittent intraperitoneal (i.p) injection of nitroglycerin (NTG). Photophobia and anxiety-like behaviors were determined in the modified elevated plus maze on days 2, 4, 6, 8, and 10 and in the light/dark box on days 3, 5, 7, 9, and 11. Blood levels of PACAP and cortisol were assessed by enzyme-linked immunosorbent (ELISA) kits. Chronic injection of NTG evoked photophobia and anxiety-like behaviors and treatment with ghrelin (150 μg/kg) for 11 days effectively attenuated photophobia and anxiety-like behaviors in the both paradigms. We further found that NTG increased the blood levels of PACAP and cortisol, which was significantly reduced by ghrelin treatment. Additionally, staining with Hematoxylin and Eosin (H&E) revealed that ghrelin reduced NTG-induced increase in the number of satellite glial cells in the trigeminal ganglion. Furthermore, for the first time we showed that repeated administrations of NTG increased white blood cell (WBC) counts and mean platelet volume (MPV), and decreased platelet counts. These results indicated that ghrelin decreased migraine associated symptoms possibly through attenuating endogenous PACAP and cortisol levels. Therefore, ghrelin may hold therapeutic potentialities in managing the chronic migraine.
Zhao, Hong-Bo; Jiang, You-Ming; Li, Xiao-Juan; Liu, Yue-Yun; Bai, Xiao-Hui; Li, Na; Chen, Jia-Xu; Liu, Qun; Yan, Zhi-Yi; Zhao, Fang-Zhou
The current study evaluated the effects of Xiao Yao San (XYS) on anxiety-like behaviors and sought to determine whether the c-Jun N-terminal kinase (JNK) signaling pathway is involved. A total of 40 rats were divided into 5 groups (n=8): the control group (deionized water, per os (p.o.)), the model group (deionized water, p.o.), the SP600125 group (surgery), the per se group (surgery), and the XYS group (3.9 g/kg/d, p.o.). A 1% dimethyl sulfoxide (DMSO) citrate buffer solution (2 µL/ventricle/d) and SP600125 (10 µg/ventricle, 2 µL/ventricle/d) were separately and bilaterally injected into the rats of the two surgery groups via the ventricular system of the brain. All but the control group underwent 14 d of chronic immobilization stress (CIS; 3 h/d). On day 15, the body weights of all of the rats were measured; additionally, the rats were subjected to the elevated plus maze (EPM) and novelty suppressed feeding (NSF) tests. Finally, JNK signaling pathway indices, including phosphorylated JNK (P-JNK), JNK, phosphorylated c-Jun (P-c-Jun) and cytochrome C (Cyt-C), were examined. After modeling, the body weight and behavioral analyses of the model rats indicated that this modeling method induced anxiety-like behaviors. P-JNK, JNK, and P-c-Jun were altered in the hippocampus of the model rats. After 14 d of treatment with XYS and SP600125, rat body weight and behaviors as well as P-JNK, JNK, and P-c-Jun had changed. However, no significant difference in Cyt-C was found. XYS improves the anxiety-like behaviors induced by CIS, which might be related to the JNK signaling pathway in the hippocampus.
Guthrie, K. M.; Lanoye, A.; Tate, D. F.; Robichaud, E.; Caccavale, L. J.; Wing, R. R.
Summary Objective Emerging adults ages 18–25 are at high risk for obesity, but are markedly underrepresented in behavioural weight loss (BWL) programs and experience lower engagement and retention relative to older adults. Purpose To utilize a mixed methods approach to inform future efforts to effectively recruit and engage this high‐risk population in BWL programs. Methods We used a convergent parallel design in which quantitative and qualitative data were given equal priority. Study 1 (N = 137, age = 21.8 + 2.2, BMI = 30.1 + 4.7) was a quantitative survey, conducted online to reduce known barriers and minimize bias. Study 2 (N = 7 groups, age = 22.3 + 2.2, BMI = 31.5 + 4.6) was a qualitative study, consisting of in person focus groups to gain greater depth and identify contextual factors unable to be captured in Study 1. Results Weight loss was of interest, but weight itself was not a central motivation; an emphasis on overall lifestyle, self‐improvement and fitness emerged as driving factors. Key barriers were time, motivation and money. Recruitment processes should be primarily online with messages tailored specifically to motivations and preferences of this age group. Preferences for a program were reduced intensity and brief, hybrid format with some in‐person contact, individual level coaching, experiential learning and peer support. Key methods of promoting engagement and retention were autonomy and choice, money and creating an optimal default. Conclusions An individually tailored lifestyle intervention that addresses a spectrum of health behaviours, promotes autonomy and emphasizes activity and fitness may facilitate recruitment and engagement in this population better than traditional BWL protocols. PMID:28090339
Plescia, Fulvio; Sardo, Pierangelo; Rizzo, Valerio; Cacace, Silvana; Marino, Rosa Anna Maria; Brancato, Anna; Ferraro, Giuseppe; Carletti, Fabio; Cannizzaro, Carla
Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10mg/kg, s.c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of both spatial orientation-acquisition and object discrimination in a simple and in a complex version of the visual task. Electrophysiological recordings were also performed in vivo, after acute PREGS systemic administration in order to investigate on the neuronal activation in the hippocampus and the perirhinal cortex. Our results indicate that, PREGS induces an improvement in spatial orientation-acquisition and in object discrimination in the simple and in the complex visual task; the behavioural responses were also confirmed by electrophysiological recordings showing a potentiation in the neuronal activity of the hippocampus and the perirhinal cortex. In conclusion, this study demonstrates that PREGS systemic administration in rats exerts cognitive enhancing properties which involve both the acquisition and utilization of spatial information, and object discrimination memory, and also correlates the behavioural potentiation observed to an increase in the neuronal firing of discrete cerebral areas critical for spatial learning and object recognition. This provides further evidence in support of the role of PREGS in exerting a protective and enhancing role on human memory.
Background Early life experiences including physical exercise, sensory stimulation, and social interaction can modulate development of the inhibitory neuronal network and modify various behaviors. In particular, alteration of parvalbumin-expressing neurons, a gamma-aminobutyric acid (GABA)ergic neuronal subpopulation, has been suggested to be associated with psychiatric disorders. Here we investigated whether rearing in enriched environment could modify the expression of parvalbumin-positive neurons in the basolateral amygdala and anxiety-like behavior. Results Three-week-old male rats were divided into two groups: those reared in an enriched environment (EE rats) and those reared in standard cages (SE rats). After 5 weeks of rearing, the EE rats showed decreased anxiety-like behavior in an open field than the SE rats. Under another anxiogenic situation, in a beam walking test, the EE rats more quickly traversed an elevated narrow beam. Anxiety-like behavior in the open field was significantly and negatively correlated with walking time in the beam-walking test. Immunohistochemical tests revealed that the number of parvalbumin-positive neurons significantly increased in the basolateral amygdala of the EE rats than that of the SE rats, while the number of calbindin-D28k-positive neurons did not change. These parvalbumin-positive neurons had small, rounded soma and co-expressed the glutamate decarboxylase (GAD67). Furthermore, the number of parvalbumin-positive small cells in the basolateral amygdala tended to positively correlate with emergence in the center arena of the open field and negatively correlated with walking time in the beam walking test. Conclusion Rearing in the enriched environment augmented the number of parvalbumin-containing specific inhibitory neuron in the basolateral amygdala, but not that of calbindin-containing neuronal phenotype. Furthermore, the number of parvalbumin-positive small neurons in the basolateral amygdala was negatively
Loprinzi, Paul D; Loenneke, Jeremy P
The purpose of this study was to examine the association between leukocyte telomere length (LTL) and mortality (outcome variable), with consideration by physical activity behaviour. Data from the 1999-2002 National Health and Nutrition Examination Survey were employed (N = 6,611; 20-85 yrs), with follow-up mortality assessment through 31 December 2006. DNA was extracted from whole blood to assess LTL via quantitative polymerase chain reaction. Compared to those in the first LTL tertile, the adjusted hazard ratio for all-cause mortality for those in the 2(nd) and 3(rd) LTL tertiles, respectively, was 0.82 (95% CI: 0.60-1.12; P = .22) and 0.76 (95% CI: 0.50-1.14; P = .18). However, after adjustments, LTL tertile 3 (vs. 1) was associated with all-cause mortality (HR = 0.37; 95% CI: 0.14-0.93; P = .03) for those who engaged in moderate-intensity exercise. Similarly, LTL was associated with CVD-specific mortality for those who engaged in moderate-intensity exercise (HR = 0.17; 95% CI: 0.04-0.73; P = .02). Longer telomeres are associated with increased survival, particularly among men and those who are active, underscoring the importance of promotion of physical activity behaviour.
Vainik, Uku; Dagher, Alain; Dubé, Laurette; Fellows, Lesley K
The worldwide increase in obesity has spurred numerous efforts to understand the regulation of eating behaviours and underlying brain mechanisms. These mechanisms can affordably be studied via neurobehavioural measures. Here, we systematically review these efforts, evaluating neurocognitive tests and personality questionnaires based on: a) consistent relationship with obesity and eating behaviour, and b) reliability. We also considered the measures’ potential to shed light on the brain mechanisms underlying these individual differences. Sixty-six neurocognitive tasks were examined. Less than 11%, mainly measures of executive functions and food motivation, yielded both replicated and reliable effects. Several different personality questionnaires were consistently related to BMI. However, further analysis found that many of these questionnaires relate closely to Conscientiousness, Extraversion and Neuroticism within the Five-Factor Model of personality. Both neurocognitive tests and personality questionnaires suggest that the critical neural systems related to individual differences in obesity are lateral prefrontal structures underpinning self-control and striatal regions implicated in food motivation. This review can guide selection of the highest yield neurobehavioural measures for future studies. PMID:23261403
Zakopoulou, Victoria; Pashou, Theodora; Tzavelas, Panagiotis; Christodoulides, Pavlos; Anna, Milona; Iliana, Kolotoura
The development of learning difficulties is associated with problems in external (executive) and extensive behaviour in a co-occurrence with psycho-emotional problems beginning from pre-school, school age, and adolescence up to adulthood. Through the current survey, we aim to emphasise the early role of learning difficulties during the school age and adolescence of prisoners and their effects on the onset of offending behaviours in adulthood, such as criminal behaviour. Altogether, we studied 117 Greek adult prisoners from 18 to 70 years old who were accused of different types or degrees of offences. Through statistical analyses, the following factors were observed with high statistical significance as early indicators of criminal behaviour in the adult lives of the prisoners: (i) learning difficulties, (ii) family problems, (iii) behaviour disorders, (iv) developmental disorders, and (v) psycho-emotional disorders. As a result, the learning difficulties were assumed to be the most decisive factor in the developmental progression of prisoners because they manifested early in the prisoners' lives, weakened the prisoners to be competitive and robust, provoked a bad self-image and low self-esteem, and, in the frame of a weak or negative family and educational environment, they accompanied antisocial behaviour and psycho-emotional disorders even from adolescence, which continued into adulthood.
Baillargeon, Lucie; Landreville, Philippe; Verreault, René; Beauchemin, Jean-Pierre; Grégoire, Jean-Pierre; Morin, Charles M.
Background Long-term use of hypnotics is not recommended because of risks of dependency and adverse effects on health. The usual clinical management of benzodiazepine dependency is gradual tapering, but when used alone this method is not highly effective in achieving long-term discontinuation. We compared the efficacy of tapering plus cognitive-behavioural therapy for insomnia with tapering alone in reducing the use of hypnotics by older adults with insomnia. Methods People with chronic insomnia who had been taking a benzodiazepine every night for more than 3 months were recruited through media advertisements or were referred by their family doctors. They were randomly assigned to undergo either cognitive-behavioural therapy plus gradual tapering of the drug (combined treatment) or gradual tapering only. The cognitive-behavioural therapy was provided by a psychologist in 8 weekly small-group sessions. The tapering was supervised by a physician, who met weekly with each participant over an 8-week period. The main outcome measure was benzodiazepine discontinuation, confirmed by blood screening performed at each of 3 measurement points (immediately after completion of treatment and at 3- and 12-month follow-ups). Results Of the 344 potential participants, 65 (mean age 67.4 years) met the inclusion criteria and entered the study. The 2 study groups (35 subjects in the combined treatment group and 30 in the tapering group) were similar in terms of demographic characteristics, duration of insomnia and hypnotic dosage. Immediately after completion of treatment, a greater proportion of patients in the combined treatment group had withdrawn from benzodiazepine use completely (77% [26/34] v. 38% [11/29]; odds ratio [OR] 5.3, 95% confidence interval [CI] 1.8–16.2; OR after adjustment for initial benzodiazepine daily dose 7.9, 95% CI 2.4–30.9). At the 12-month follow-up, the favourable outcome persisted (70% [23/33] v. 24% [7/29]; OR 7.2, 95% CI 2.4–23.7; adjusted OR 7
Deb, S.; Chaplin, R.; Sohanpal, S.; Unwin, G.; Soni, R.; Lenotre, L.
Background: Psychotropic medications are used to manage behaviour problems in adults with intellectual disability (ID). One group of psychotropic medication are mood stabilizers such as lithium and some antiepileptic drugs. Method: A comprehensive systematic review was performed to determine the evidence base for the effectiveness of mood…
Unwin, Gemma L.; Deb, Shoumitro
The aim was to investigate prescribing practices surrounding the use of medication for the management of behavioural problems in adults with intellectual disabilities with reference to a national guideline development project. A case note review methodology was employed to explore adherence to the audit criteria that were derived from the…
Mills, S D H; Tanner, L M; Adams, J
A large body of research confirms that food advertising affects the food preferences and behaviour of children. The impact of food advertising on adults is less clear. We conducted a systematic review exploring the effects of advertising of food and non-alcoholic drinks (referred to as 'food' throughout) on food-related behaviour, attitudes and beliefs in adult populations. We searched seven electronic databases, grey literature sources, and references and citations of included material for experimental studies written in English investigating the effects of commercial food advertising on the food-related behaviours, attitudes and beliefs of adults aged 16 years and over. Nine studies, rated moderate to poor quality, were included in the review; all were from developed countries and explored the impact of televised food advertising. Overall, the results did not show conclusively whether or not food advertising affects food-related behaviour, attitudes or beliefs in adults, but suggest that the impact varies inconsistently within subgroups, including gender, weight and existing food psychology. The identification of a small number of relevant studies, none of which were high quality, and with substantial heterogeneity, highlights the need for further research. Future studies investigating longer term outcomes, diverse advertising formats, and in countries with different levels of economic development will be of particular value.
Liveris, Christine; Cavanagh, Rob
National Vocational Education and Training (VET) reforms have resulted in an increasing proportion of young adults in VET programs in Western Australia. A challenge for practitioners is to help them develop skills and attributes to facilitate lifelong learning. A need for further research into the self-regulation behaviour of this cohort has been…
Keller, Kristin; Rodríguez López, Santiago; Carmenate Moreno, Margarita M
The study aims to evaluate the association between abdominal obesity with meal intake behaviour such as having a forenoon meal, having an afternoon meal and snacking. This cross-sectional study includes n = 1314 participants aged 20-79 who were interviewed during the Cardiac health "Semanas del Corazon" events in four Spanish cities (Madrid, Las Palmas, Seville and Valencia) in 2008. Waist circumference, weight and height were assessed to determine abdominal obesity (waist circumference: ≥88 cm in women and ≥102 cm in men) and BMI, respectively. The intake of forenoon and afternoon meal and snacking between the participants' regular meals were assessed with a questionnaire that also included individual risk factors. The information obtained about diet was required to calculate an Unhealthy Habit Score and a score reflecting the Achievement of Dietary Guidelines. Adjusted logistic regressions were used to examine the association between abdominal obesity and the mentioned meal intake behaviour controlling for sex, age, individual risk factors, BMI and diet. Having an afternoon meal (OR 0.60; 95% CI (0.41-0.88)) was negatively associated with abdominal obesity after adjusting for all confounders, whereas the positive association of snacking (OR 1.39; 95% CI (1.05-1.85)) was not independent of BMI (OR 1.25; 95% CI (0.84-1.87)). Taking a forenoon meal did not show any associations (OR 0.92; 95% CI (0.63-1.34)) with abdominal obesity. The results obtained could be helpful in the promotion of healthy habits in nutritional education programmes and also in health programmes preventing abdominal obesity.
Babovic, Daniela; Jiang, Luning; Gantois, Ilse; Lawrence, Andrew J; Ferreri, Vincenzo; Schütz, Günter; Waddington, John L; Drago, John
In this study we characterize the behavioural and cellular phenotype of mutant (MUT) mice with progressive loss of D1 dopamine receptor (Drd1a)-expressing cells. Adult [14-19 weeks] MUT mice showed intact working memory in the spontaneous alternation test but evidenced anxiety-like behaviour in the elevated plus maze and the light-dark test. The ethogram of mature adult MUT [average age 22 weeks] was compared with that of young adult MUT mice [average age 12 weeks]. While MUT mice evidenced hyperactivity over initial exploration at both time points, the topography of hyperactivity shifted. Moreover, initial hyperactivity was sustained over habituation at 12 weeks, but not at 22 weeks. Thus, by 22 weeks MUT mice evidenced shifts in, and mitigation of, these early phenotypic effects. However, orofacial behaviours of chewing and sifting were reduced similarly at 12 and 22 weeks. These data support the hypothesis that aspects of the mutant phenotype change with time. Quantitative autoradiography at 20 weeks revealed loss of D1-like dopamine receptor binding in the entire basal ganglia, with upregulated D2-like binding. There appear to be topographically specific interactions between normal maturational processes and compensatory mechanisms evoked subsequent to targeted ablation of D1 dopamine receptor-expressing cells. Understanding the mechanistic bases of mitigation vs persistence of individual phenotypes in relation to neural adaptation consequent to cell loss may lead to novel therapeutic strategies for basal ganglia disorders.
Chang, Chia-Yu; Guo, How-Ran; Tsai, Wan-Chen; Yang, Kai-Lin; Lin, Li-Chuan; Cheng, Tain-Junn; Chuu, Jiunn-Jye
Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.
Palotai, Miklós; Telegdy, Gyula; Jászberényi, Miklós
Orexins are hypothalamic neuropeptides, which are involved in several physiological functions of the central nervous system, including anxiety and stress. Several studies provide biochemical and behavioral evidence about the anxiogenic action of orexin A. However, we have little evidence about the underlying neuromodulation. Therefore, the aim of the present study was to investigate the involvement of neurotransmitters in the orexin A-induced anxiety-like behavior in elevated plus maze (EPM) test in mice. Accordingly, mice were pretreated with a non-selective muscarinic cholinergic antagonist, atropine; a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, bicuculline; a D2, D3, D4 dopamine receptor antagonist, haloperidol; a non-specific nitric oxide synthase (NOS) inhibitor, nitro-l-arginine; a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a β-adrenergic receptor antagonist, propranolol 30min prior to the intracerebroventricular administration of orexin A. The EPM test started 30min after the i.c.v. injection of the neuropeptide. Our results show that orexin A decreases significantly the time spent in the arms (open/open+closed) and this action is reversed by bicuculline, phenoxybenzamine and propranolol, but not by atropine, haloperidol or nitro-l-arginine. Our results provide evidence for the first time that the orexin A-induced anxiety-like behavior is mediated through GABA-A-ergic, α- and β-adrenergic neurotransmissions, whereas muscarinic cholinergic, dopaminergic and nitrergic neurotransmissions may not be implicated.
Noschang, Cristie Grazziotin; Pettenuzzo, Leticia Ferreira; von Pozzer Toigo, Eduardo; Andreazza, Ana Cristina; Krolow, Rachel; Fachin, Andrelisa; Avila, Mônica Colpini; Arcego, Danusa; Crema, Leonardo Machado; Diehl, Luísa Amália; Gonçalvez, Carlos Alberto; Vendite, Deusa; Dalmaz, Carla
Caffeine is widely consumed in beverages and food, and its consumption in high doses is associated with anxiety increase. Stress situations are often associated to coffee consumption, and have a strong influence on oxidative DNA damage. As there are sex-specific differences in many metabolic, neurochemical and behavioral aspects, the aim of this study is to verify the interaction between chronic consumption of caffeine and chronic stress on anxiety and DNA breaks in the hippocampus on male and female rats. Wistar rats were submitted to restraint stress for at least 50 days. The diet consisted of standard rat chow and caffeine 0.3 or 1 g/L in drinking water "ad libitum" as the only drinking source. Controls received tap water. Anxiety-like behavior and DNA breaks in the hippocampus were evaluated. Caffeine consumption and chronic stress increased anxiety-like behavior as well as DNA breaks in the hippocampus of male rats. No effect on these parameters was observed in females. These results may be related to the presence of estradiol, which may have anxiolytic and neuroprotective properties.
Akillioglu, Kubra; Babar Melik, Emine; Melik, Enver; Kocahan, Sayad
N-methyl-D-aspartate (NMDA) receptors play an important role in brain maturation and developmental processes. It is known that growing up in an enriched environment has effects on emotional and cognitive performance. In our study, we evaluated the effects of physically enriched environment on the emotional and cognitive functions of the adult brain in the setting of previous NMDA receptor hypoactivity during the critical developmental period of the nervous system. In this study, NMDA receptor blockade was induced 5-10 days postnatally (PD5-10) using MK-801 in mice Balb/c (twice a day 0.25 mg/kg, for 5 days, intraperitoneal). MK-801 was given to developing mice living in a standard (SE) and an enrichment environment (EE) and once the animals reached adulthood, emotional behaviors were evaluated using an open field test (OF) and an elevated plus maze (EPM) test whereas cognitive processes were evaluated using the Morris water-maze (MWM). The EE group showed decreased locomotor activity (p<0.05) in the OF and increased exploratory behaviour (p<0.01) and decreased fear of heights/anxiety-like behaviour (p<0.05) in the EPM test. The EE had positive effects on spatial learning in the MWM (p<0.05). Blockade of the NMDA receptor increased the fear of height (p<0.05), decreased exploratory behaviour and locomotor activity (p<0.001). Also, it led to decreased spatial learning (p<0.05). The decreases in spatial learning and exploratory behaviours and the increase in fear of heights/anxiety-like behaviour with NMDA receptor blockade was not reversed by EE. NMDA receptor blockade during the critical period of development led to deterioration in the emotional and cognitive processes during adulthood. An enriched environmental did not reverse the deleterious effects of the NMDA receptor blockade on emotional and cognitive functions.
Background Research suggests that the growing prevalence of obesity may be related to the influence of the health behaviours of peers. We look at clustering of exercise and eating behaviours amongst a previously unstudied group, young adults in Sweden. Previous research has mainly been conducted in the United States and Britain, countries that have relatively high rates of obesity. Methods Using ego-alter dyads from the egocentric network data as the unit of analysis, we conduct logistic regressions to investigate the association between ego and alter exercise and eating behaviours. Results Respondents have a significantly greater probability of engaging in regular exercise and eating healthily if a nominated peer also does so. Furthermore, the degree to which this behavior is shared is modulated by the strength of the relationship between the two individuals, with a greater probability of engaging in these behaviours observed when the relationship with the nominated peer is strong relative to when the relationship is weak. However, we find that ego-alter homogeneity in terms of gender and migration status was not associated with a significantly greater probability of behaving in a similar manner to a nominated peer. Furthermore, the status of the nominated peer as a relative or not did not impact the probability that the ego would engage in similar health behaviours to that alter. Conclusions We observe strong associations between ego and alter health behaviours for young adults, consistent with previous research. Although we cannot draw causal inferences, these results suggest that the health behaviours of an individual’s peers may play a role in shaping their own health behaviours. PMID:23981951
Henzi, S P; Lawes, M
Troops comprising a high density population of samango monkeys (Cercopithecus mitis) in Natal province, South Africa, experienced an influx of adult males during the breeding season. Observation of one troop revealed that these males competed with one another and with two resident males for access to receptive females. Although both sexes initiated copulation, attempts to do so were more often successful if female-initiated. Males did not interact with non-receptive females and there were no recorded attempts at infanticide. Male-male interactions were agonistic in the presence of receptive females and neutral at other times. No ritualized displays of dominance and subordinance were seen. The significance of these observations for male reproductive strategies is discussed.
Takashima, Shigeo; Mkrtchyan, Marianna; Younossi-Hartenstein, Amelia; Merriam, John R; Hartenstein, Volker
The intestinal tract maintains proper function by replacing aged cells with freshly produced cells that arise from a population of self-renewing intestinal stem cells (ISCs). In the mammalian intestine, ISC self renewal, amplification and differentiation take place along the crypt-villus axis, and are controlled by the Wnt and hedgehog (Hh) signalling pathways. However, little is known about the mechanisms that specify ISCs within the developing intestinal epithelium, or about the signalling centres that help maintain them in their self-renewing stem cell state. Here we show that in adult Drosophila melanogaster, ISCs of the posterior intestine (hindgut) are confined to an anterior narrow segment, which we name the hindgut proliferation zone (HPZ). Within the HPZ, self renewal of ISCs, as well as subsequent proliferation and differentiation of ISC descendants, are controlled by locally emanating Wingless (Wg, a Drosophila Wnt homologue) and Hh signals. The anteriorly restricted expression of Wg in the HPZ acts as a niche signal that maintains cells in a slow-cycling, self-renewing mode. As cells divide and move posteriorly away from the Wg source, they enter a phase of rapid proliferation. During this phase, Hh signal is required for exiting the cell cycle and the onset of differentiation. The HPZ, with its characteristic proliferation dynamics and signalling properties, is set up during the embryonic phase and becomes active in the larva, where it generates all adult hindgut cells including ISCs. The mechanism and genetic control of cell renewal in the Drosophila HPZ exhibits a large degree of similarity with what is seen in the mammalian intestine. Our analysis of the Drosophila HPZ provides an insight into the specification and control of stem cells, highlighting the way in which the spatial pattern of signals that promote self renewal, growth and differentiation is set up within a genetically tractable model system.
Background People with intellectual disability have significantly higher age-adjusted rates of mortality and morbidity (including obesity) than their non-disabled peers. They are also significantly less likely to be physically active. Methods Secondary analysis of de-identified cross-sectional data from the first two waves of Understanding Society, a new longitudinal study focusing on the life experiences of UK citizens. Interviews were undertaken with 50,994 individuals aged 16 and over in Wave 1 and 54,585 in Wave 2. Of these, 520 participants age 16–49 (1.8% of the unweighted age-restricted sample) were identified at either Wave 1 or Wave 2 as having self-reported intellectual impairments. Results British adults with self-reported intellectual impairments have higher rates of obesity, inactivity, tobacco and alcohol use and poorer nutrition than their non-disabled peers. Adjusting risk estimates for between group differences in age, gender and exposure to material hardship indicated that a significant proportion of their increased risk of obesity, tobacco use and poorer nutrition may be attributable to their poorer living conditions (rather than their self-reported intellectual impairments per se). Conclusions People with intellectual disabilities should begin to be regarded as a ‘vulnerable’ group in the context of public health policy and practice. PMID:24588837
GABA-BZD Receptor Modulating Mechanism of Panax quinquefolius against 72-h Sleep Deprivation Induced Anxiety like Behavior: Possible Roles of Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation
Chanana, Priyanka; Kumar, Anil
Rationale: Panax quinquefolius (American Ginseng) is known for its therapeutic potential against various neurological disorders, but its plausible mechanism of action still remains undeciphered. GABA (Gamma Amino Butyric Acid) plays an important role in sleep wake cycle homeostasis. Thus, there exists rationale in exploring the GABA-ergic potential of Panax quinquefolius as neuroprotective strategy in sleep deprivation induced secondary neurological problems. Objective: The present study was designed to explore the possible GABA-ergic mechanism in the neuro-protective effect of Panax quinquefolius against 72-h sleep deprivation induced anxiety like behavior, oxidative stress, mitochondrial dysfunction, HPA-axis activation and neuroinflammation. Materials and Methods: Male laca mice were sleep deprived for 72-h by using Grid suspended over water method. Panax quinquefolius (American Ginseng 50, 100, and 200 mg/kg) was administered alone and in combination with GABA modulators (GABA Cl− channel inhibitor, GABA-benzodiazepine receptor inhibitor and GABAA agonist) for 8 days, starting 5 days prior to 72-h sleep deprivation period. Various behavioral (locomotor activity, mirror chamber test), biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels), mitochondrial complexes, neuroinflammation marker (Tumor Necrosis Factor, TNF-alpha), serum corticosterone, and histopathological sections of brains were assessed. Results: Seventy two hours sleep deprivation significantly impaired locomotor activity, caused anxiety-like behavior, conditions of oxidative stress, alterations in mitochondrial enzyme complex activities, raised serum corticosterone levels, brain TNFα levels and led to neuroinflammation like signs in discrete brain areas as compared to naive group. Panax quinquefolius (100 and 200 mg/kg) treatment restored the behavioral, biochemical, mitochondrial, molecular and histopathological alterations. Pre-treatment of GABA Cl− channel
Shibata, Shoyo; Iinuma, Munekazu; Soumiya, Hitomi; Fukumitsu, Hidefumi; Furukawa, Yoshiko; Furukawa, Shoei
We characterized mice administered corticosterone (CORT) at a dose of 20 mg/kg for 3 weeks to determine their suitability as a model of mood disorders and found that the time immobilized in the tail suspension test was longer and the time spent in the open arms of the elevated plus-maze test was shorter than those of the vehicle-treated group, findings demonstrating that chronic CORT induced both depression-like and anxiety-like behaviors. Furthermore, the levels of phosphorylated extracellular signal-regulated kinase (pERK) 1/2 in the hippocampus and cerebral cortex were reduced in the CORT-treated group. Using this model, we investigated the protective effect of the ester, thioester, and amide compounds of 2-decenoic acid derivatives (termed compounds A, B, and C, respectively). The potency of the protective activity against the CORT-induced depression-like or anxiety-like behaviors and the reduction in pERK1/2 level were found to be in the following order: compound B > compound C > compound A. Therefore, we further investigated the therapeutic activity of only compound B, and its effect on depression-like behavior was observed after oral administration for 1 or 2 weeks, and its effect on anxiety-like behavior was observed after oral administration for 3 weeks. The ratios of phosphorylated ERK1/2, Akt, and cAMP-response element-binding protein to their respective nonphosphorylated forms were smaller in the CORT-treated group than in the vehicle-treated group; however, subsequent treatment with compound B at either 0.3 or 1.5 mg/kg significantly ameliorated this reduction. Compound B appeared to elicit intracellular signaling, similar to that elicited by brain-derived neurotrophic factor, and its mode of action was shown to be novel and different from that of fluvoxamine, a currently prescribed drug for mood disorders. PMID:26038707
Ago, Yukio; Tanaka, Tatsunori; Ota, Yuki; Kitamoto, Mari; Imoto, Emina; Takuma, Kazuhiro; Matsuda, Toshio
Rearing in crowded conditions is a psychosocial stressor that affects biological functions. The effects of continuous crowding for many days have been studied, but those of crowding over a limited time have not. In this study, we examined the effects of night-time or daytime crowding over 2 weeks on behavior in adolescent and adult mice. Crowding (20 mice/cage) in either the night-time or daytime did not affect locomotor activity in the open field test or cognitive function in the fear conditioning test. In contrast, night-time crowding, but not daytime crowding, had an anxiolytic effect in the elevated plus-maze test and increased social interaction in adolescent mice, but not in adult mice. The first night-time, but not daytime, crowding increased plasma corticosterone levels in adolescent mice, although night-time crowding over 2 weeks did not affect the corticosterone levels. Furthermore, no significant effects of the first crowding were observed in adult mice. In a second crowding condition (six mice/small cage), the anxiolytic-like effects of night-time crowding and the change in plasma corticosterone levels were not observed, suggesting that the density of mice is not important for the behavioral consequences of crowding. Night-time crowding did not affect neurotrophic/growth factor levels and hippocampal neurogenesis in adolescent mice. These findings suggest that night-time crowding leads to anxiolytic-like behaviors in adolescent mice, and imply that night-time crowding stress in adolescence may be beneficial to brain functions.
Background Tobacco consumption peak in developed countries has passed, however, it is on the increase in many developing countries. Apart from cigarettes, consumption of local hand-rolled cigarettes such as bidi and rokok daun are prevalent in specific communities. Although factors associated with smoking initiation and cessation has been investigated elsewhere, the only available data for Malaysia is on prevalence. This study aims to investigate factors associated with smoking initiation and cessation which is imperative in designing intervention programs. Methods Data were collected from 11,697 adults by trained recording clerks on sociodemographic characteristics, practice of other risk habit and details of smoking such as type, duration and frequency. Smoking commencement and cessation were analyzed using the Kaplan-Meier estimates and log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to calculate the hazard rate ratios. Results Males had a much higher prevalence of the habit (61.7%) as compared to females (5.8%). Cessation was found to be most common among the Chinese and those regularly consuming alcoholic beverages. Kaplan-Meier plot shows that although males are more likely to start smoking, females are found to be less likely to stop. History of betel quid chewing and alcohol consumption significantly increase the likelihood of commencement (p < 0.0001), while cessation was least likely among Indians, current quid chewers and kretek users (p < 0.01). Conclusions Gender, ethnicity, history of quid chewing and alcohol consumption have been found to be important factors in smoking commencement; while ethnicity, betel quid chewing and type of tobacco smoked influences cessation. PMID:22429627
Sánchez-García, C; Alonso, M E; Tizado, E J; Pérez, J A; Armenteros, J A; Gaudioso, V R
The aim of this work was to improve natural anti-predator behaviour of farm-reared gamebirds. We evaluated the anti-predator behaviour of reared red-legged partridge Alectoris rufa chicks kept in brooder houses in large groups (>350 chicks), trained and not trained by parent red-legged partridges acting as experienced tutors. The experiment consisted of two conditioned tests (a raptor model and a human) and two control tests, which were conducted during three consecutive phases of life (1-4, 15-17 and 30-32 d after hatching). The motor anti-predator behaviour, its duration, the intensity of response in chicks and alarm calls elicited by adults were recorded. Tutors elicited aerial alarm calls (76% of tests) and showed prolonged crouching (59% of tests) in response to the raptor model whereas uttering the ground alarm call (73% of tests) and showing vigilance behaviour (78% of tests) was the main pattern during the human test. Trained and not trained chicks showed similar motor behaviour in response to the raptor model (crouching) and the human test (escaping), but frequency of strong responses (all chicks responding) from chicks trained with tutors was double that of chicks trained without them, and chicks trained with tutors showed a higher frequency of long responses (41-60 s). This study indicates that anti-predator training programmes before release may improve behaviour of farm-reared partridges which may confer benefits to survival of birds.
Steinmann, Andrea; Priotto, José; Sommaro, Lucia; Polop, Jaime
This research was carried out to examine the hypothesis that the absence of fathers promotes a different spacing behaviour in juveniles Calomys musculinus at the beginning of the breeding period. The study was carried out in four 0.25-ha enclosures (two control and two experimental), in a natural pasture, between November 2003 and February 2004. In this study the fathers were removed from the experimental enclosures after juveniles were born. Home-range size depended on sex of juveniles and treatment (father removal). In control and experimental enclosures, female home-range sizes were always smaller than male home-ranges. Male home-ranges were always larger in experimental enclosures than in control enclosures. Treatment and overlap type (intra- and inter-sexual) were not independent. The overlap proportions of male home-ranges were greatest in experimental enclosures than in control enclosures, in both the overlap types (male/male, males/females). The intra- (females/females) and inter-sexual (females/males) overlap proportions of female home-ranges were independent of treatment. In C. musculinus, at the beginning of the breeding period and in absence of adult males, juvenile males increase their home-range size and therefore the degree of inter- and intra-sexual home-range overlap as a mechanism for enlarging the number of receptive females that they encounter.
Quarta, Eros; Bravi, Riccardo; Scambi, Ilaria; Mariotti, Raffaella; Minciacchi, Diego
Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease primarily characterized by motor neuron death, causes damages beyond motor-related areas. In particular, cognitive impairments and hippocampal damage have been reported in ALS patients. We investigated spatial navigation learning and hippocampal interneurons in a mutant SOD1(G93A) mouse (mSOD1) model of ALS. Behavioral tests were performed by using presymptomatic mSOD1 mice. General motor activity was comparable to that of wild-type mice in the open-field test, in which, however mSOD1 exhibited increased anxiety-like behavior. In the Barnes maze test, mSOD1 mice displayed a delay in learning, outperformed wild-type mice during the first probe trial, and exhibited impaired long-term memory. Stereological counts of parvalbumin-positive interneurons, which are crucial for hippocampal physiology and known to be altered in other central nervous system regions of mSOD1 mice, were also performed. At postnatal day (P) 56, the population of parvalbumin-positive interneurons in mSOD1 mice was already reduced in CA1 and in CA3, and at P90 the reduction extended to the dentate gyrus. Loss of parvalbumin-positive hippocampal interneurons occurred mostly during the presymptomatic stage. Western blot analysis showed that hippocampal parvalbumin expression levels were already reduced in mSOD1 mice at P56. The hippocampal alterations in mSOD1 mice could at least partly account for the increased anxiety-like behavior and deficits in spatial navigation learning. Our study provides evidence for cognitive alterations and damage to the γ-aminobutyric acid (GABA)ergic system in the hippocampus of murine ALS, thereby revealing selective deficits antecedent to the onset of motor symptoms.
Bassi, Gabriel Shimizu; de Carvalho, Milene Cristina; Brandão, Marcus Lira
The amygdala, together with the dorsal periaqueductal gray (dPAG), medial hypothalamus, and deep layers of the superior and inferior colliculi, constitutes the encephalic aversion system, which has been considered the main neural substrate for the organization of fear and anxiety. The basolateral nucleus of the amygdala (BLA) acts as a filter for aversive stimuli to higher structures while the central (CeA) and the medial (MeA) nuclei constitute the output for the autonomic and somatic components of the emotional reaction through major projections to the limbic and brainstem regions. Although some findings point to the distinct participation of the substance P (SP) and the NK1 receptors system in the different nuclei of the amygdala on the expression of emotional behaviors, it is not clear if this system modulates anxiety-like responses in the distinct nuclei of the amygdala as well as the dPAG. Thus, it was investigated if the injection of SP into the BLA, CeA, or MeA affects the expression of anxiety-like responses of rats submitted to the elevated plus-maze (EPM) test and, if the effects are mediated by NK1 receptors. The results showed that SP and Sar-Met-SP (NK1 receptor selective agonist) injected into the CeA and MeA, but not into the BLA, caused anxiogenic-like effects in the EPM. Altogether, the data indicates that the SP may mimic the effects of anxiogenic stimuli via NK1 receptor activation only in the CeA and MeA (amygdala's nuclei output) and may activate the neural mechanisms involved in the defensive reaction genesis. The SP/NK1 receptors system activation may be phasically involved in very specific aspects of anxiety behaviors.
Kuniishi, Hiroshi; Ichisaka, Satoshi; Matsuda, Sae; Futora, Eri; Harada, Riho; Hata, Yoshio
The orbitofrontal cortex (OFC) is involved in emotional processing, and orbitofrontal abnormalities have often been observed in various affective disorders. Thus, chronic dysfunction of the OFC may cause symptoms of affective disorders, such as anxiety, depression and impulsivity. Previous studies have investigated the effect of orbitofrontal dysfunction on anxiety-like behavior and impulsive aggression in rodents, but the results are inconsistent possibly reflecting different methods of OFC inactivation. These studies used either a lesion of the OFC, which may affect other brain regions, or a transient inactivation of the OFC, whose effect may be restored in time and not reflect effects of chronic OFC dysfunction. In addition, there has been no study on the effect of orbitofrontal inactivation on depression-like behavior in rodents. Therefore, the present study examined whether chronic inactivation of the OFC by continuous infusion of a GABAA receptor agonist, muscimol, causes behavioral abnormalities in rats. Muscimol infusion inactivated the ventral and lateral part of the OFC. Following a week of OFC inactivation, the animals showed an increase in anxiety-like behavior in the open field test and light-dark test. Impulsive aggression was also augmented in the chronically OFC-inactivated animals because they showed increased frequency of fighting behavior induced by electric foot shock. On the other hand, chronic OFC inactivation reduced depression-like behavior as evaluated by the forced swim test. Additionally, it did not cause a significant change in corticosterone secretion in response to restraint stress. These data suggest that orbitofrontal neural activity is involved in the regulation of anxiety- and depression-like behaviors and impulsive aggression in rodents. PMID:28167902
Teixeira, A M; Pase, C S; Boufleur, N; Roversi, K; Barcelos, R C S; Benvegnú, D M; Segat, H J; Dias, V T; Reckziegel, P; Trevizol, F; Dolci, G S; Carvalho, N R; Soares, F A A; Rocha, J B T; Emanuelli, T; Bürger, M E
Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise.
Patki, Gaurav; Solanki, Naimesh; Atrooz, Fatin; Allam, Farida; Salim, Samina
In the present study, we have examined the behavioral and biochemical effect of induction of psychological stress using a modified version of the resident-intruder model for social stress (social defeat). At the end of the social defeat protocol, body weights, food and water intake were recorded, depression and anxiety-like behaviors as well as memory function was examined. Biochemical analysis including oxidative stress measurement, inflammatory markers and other molecular parameters, critical to behavioral effects were examined. We observed a significant decrease in the body weight in the socially defeated rats as compared to the controls. Furthermore, social defeat increased anxiety-like behavior and caused memory impairment in rats (P<0.05). Socially defeated rats made significantly more errors in long term memory tests (P<0.05) as compared to control rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK1/2), and an inflammatory marker, interleukin (IL)-6 were activated (P<0.05), while the protein levels of glyoxalase (GLO)-1, glutathione reductase (GSR)-1, calcium/calmodulin-dependent protein kinase type (CAMK)-IV, cAMP-response-element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were significantly less (P<0.05) in the hippocampus, but not in the prefrontal cortex and amygdala of socially defeated rats, when compared to control rats. We suggest that social defeat stress alters ERK1/2, IL-6, GLO1, GSR1, CAMKIV, CREB, and BDNF levels in specific brain areas, leading to oxidative stress-induced anxiety-depression-like behaviors and as well as memory impairment in rats.
Li, Xia; Risbrough, Victoria B; Cates-Gatto, Chelsea; Kaczanowska, Katarzyna; Finn, M G; Roberts, Amanda J; Markou, Athina
γ-Aminobutyric acid B (GABAB) receptor activation is a potential therapeutic approach for the treatment of drug addiction, pain, anxiety, and depression. However, full agonists of this receptor induce side-effects, such as sedation, muscle relaxation, tolerance, and cognitive disruption. Positive allosteric modulators (PAMs) of the GABAB receptor may have similar therapeutic effects as agonists with superior side-effect profiles. The present study behaviorally characterized N-([1R,2R,4S]-bicyclo[2.2.1]hept-2-yl)-2-methyl-5-(4-[trifluoromethyl]phenyl)-4-pyrimidinamine (BHF177), a GABAB receptor PAM, in mouse models of anxiety-like behavior, learning and memory. In addition, the effects of BHF177 were compared with the agonist baclofen. Unlike the anxiolytic chlordiazepoxide, baclofen (0.5, 1.5, and 2.5 mg/kg, intraperitoneally) and BHF177 (10, 20, and 40 mg/kg, orally) had no effect on anxiety-like behavior in the elevated plus maze, light/dark box, or Vogel conflict test. Baclofen increased punished drinking in the Vogel conflict test, but this effect may be attributable to the analgesic actions of baclofen. At the highest dose tested (2.5 mg/kg), baclofen-treated mice exhibited sedation-like effects (i.e., reduced locomotor activity) across many of the tests, whereas BHF177-treated mice exhibited no sedation-like effects. BHF177 exhibited pro-convulsion properties only in mice, but not in rats, indicating that this effect may be species-specific. At doses that were not sedative or pro-convulsant, baclofen and BHF177 had no selective effects on fear memory retrieval in contextual and cued fear conditioning or spatial learning and memory in the Barnes maze. These data suggest that BHF177 has little sedative activity, no anxiolytic-like profile, and minimal impairment of learning and memory in mice.
Kulesskaya, Natalia; Voikar, Vootele
Light-dark box and open field are conventional tests for assessment of anxiety-like behavior in the laboratory mice, based on approach-avoidance conflict. However, except the basic principles, variations in the equipment and procedures are very common. Therefore, contribution of certain methodological issues in different settings was investigated. Three inbred strains (C57BL/6, 129/Sv, DBA/2) and one outbred stock (ICR) of mice were used in the experiments. An effect of initial placement of mice either in the light or dark compartment was studied in the light-dark test. Moreover, two tracking systems were applied - position of the animals was detected either by infrared sensors in square box (1/2 dark) or by videotracking in rectangular box (1/3 dark). Both approaches revealed robust and consistent strain differences in the exploratory behavior. In general, C57BL/6 and ICR mice showed reduced anxiety-like behavior as compared to 129/Sv and DBA/2 strains. However, the latter two strains differed markedly in their behavior. DBA/2 mice displayed high avoidance of the light compartment accompanied by thigmotaxis, whereas the hypoactive 129 mice spent a significant proportion of time in risk-assessment behavior at the opening between two compartments. Starting from the light side increased the time spent in the light compartment and reduced the latency to the first transition. In the open field arena, black floor promoted exploratory behavior - increased time and distance in the center and increased rearing compared to white floor. In conclusion, modifications of the apparatus and procedure had significant effects on approach-avoidance behavior in general whereas the strain rankings remained unaffected.
Hendershott, Taylor R; Cronin, Marie E; Langella, Stephanie; McGuinness, Patrick S; Basu, Alo C
The influence of housing on cognition and emotional regulation in mice presents a problem for the study of genetic and environmental risk factors for neuropsychiatric disorders: standard laboratory housing may result in low levels of cognitive function or altered levels of anxiety that leave little room for assessment of deleterious effects of experimental manipulations. The use of enriched environment (EE) may allow for the measurement of a wider range of performance in cognitive domains. Cognitive and behavioral effects of EE in male mice have not been widely reproduced, perhaps due to variability in the application of enrichment protocols, and the effects of EE in female mice have not been widely studied. We have developed an EE protocol using common laboratory equipment that, without a running wheel for exercise, results in significant cognitive and behavioral effects relative to standard laboratory housing conditions. We compared male and female wild-type C57BL/6J mice reared from weaning age in an EE to those reared in a standard environment (SE), using common measures of anxiety-like behavior, sensory gating, sociability, and spatial learning and memory. Sex was a significant factor in relevant elevated plus maze (EPM) measures, and bordered on significance in a social interaction (SI) assay. Effects of EE on anxiety-like behavior and sociability were indicative of a general increase in exploratory activity. In male and female mice, EE resulted in reduced prepulse inhibition (PPI) of the acoustic startle response, and enhanced spatial learning and use of spatially precise strategies in a Morris water maze task.
de Lima, Denise Sandrelly Cavalcanti; Francisco, Elian da Silva; Lima, Cássia Borges; Guedes, Rubem Carlos Araújo
In mammals, L-glutamine (Gln) can alter the glutamate-Gln cycle and consequently brain excitability. Here, we investigated in developing rats the effect of treatment with different doses of Gln on anxiety-like behavior, cortical spreading depression (CSD), and microglial activation expressed as Iba1-immunoreactivity. Wistar rats were suckled in litters with 9 and 15 pups (groups L 9 and L 15; respectively, normal size- and large size litters). From postnatal days (P) 7-27, the animals received Gln per gavage (250, 500 or 750 mg/kg/day), or vehicle (water), or no treatment (naive). At P28 and P30, we tested the animals, respectively, in the elevated plus maze and open field. At P30-35, we measured CSD parameters (velocity of propagation, amplitude, and duration). Fixative-perfused brains were processed for microglial immunolabeling with anti-IBA-1 antibodies to analyze cortical microglia. Rats treated with Gln presented an anxiolytic behavior and accelerated CSD propagation when compared to the water- and naive control groups. Furthermore, CSD velocity was higher (p < 0.001) in the L 15 compared to the L 9 condition. Gln treatment increased Iba1 immunolabeling both in the parietal cortex and CA1 hippocampus, indicating microglial activation. The Gln effect was dose-dependent for anxiety-like behavior and CSD in both litter sizes, and for microglial activation in the L 15 groups. Besides confirming previous electrophysiological findings (CSD acceleration after Gln), our data demonstrate for the first time a behavioral and microglial activation that is associated with early Gln treatment in developing animals, and that is possibly operated via changes in brain excitability.
Kim, S.; Zhang, S.; Choi, KH; Reister, R.; Do, Chi; Baykiz, A.F.; Gershenfeld, H.K.
Background Identification of the genes underlying psychiatric illness remains a thorny problem. Previously, Quantitative Trait Loci (QTL) for anxiety-like behaviors and beta-carboline-induced seizure vulnerability have been mapped to the distal portion of mouse chromosome 10, using crosses of A/J and C57BL6 mice. Methods An interval specific congenic strain for this chromosomal 10 region facilitated the genetic dissection of novelty-induced exploratory behaviors. Results By microarray studies, an unsuspected E3 Ubiquitin Ligase, Ring Finger 41 (Rnf41) was differentially expressed in the region of interest, being upregulated in the hippocampi of B6 compared to A/J as well as congenic A.B6chr10 vs. A/J. By qRT-PCR, Rnf41 expression levels were significantly increased 1.5 and 1.3-fold in the hippocampi of C57BL6/J and A.B6chr10 mice compared to A/J mice, respectively. Protein levels of Rnf41 were increased in hippocampi of B6 mice compared to A/J mice across postnatal development with a 5.5-fold difference at P56. Yeast two hybrid studies searching for Rnf41 binding partners in fetal hippocampus identified several potential targets. An interaction between Rnf41 and NogoA was validated by GST-Rnf41 pulldown experiments. Re-analyzing a microarray database of human post-mortem prefrontal cortex (Brodmann’s Area 46/10), RNF41 mRNA expression levels were reduced significantly in patients with major depression and bipolar disorder compared to unaffected controls and confirmed by qRT-PCR. Conclusion Overall, Rnf41 is nominated as a candidate gene for anxiety-like behaviors, depression, and vulnerability to seizures. RNF41 and its binding partners suggest molecular pathways underlying behavior, highlighting a potential role for the ubiquitin proteasome system in psychiatric illness. PMID:18986647
Gainey, Stephen J.; Kwakwa, Kristin A.; Bray, Julie K.; Pillote, Melissa M.; Tir, Vincent L.; Towers, Albert E.; Freund, Gregory G.
Obesity-associated comorbidities such as cognitive impairment and anxiety are increasing public health burdens that have gained prevalence in children. To better understand the impact of childhood obesity on brain function, mice were fed with a high-fat diet (HFD) from weaning for 1, 3 or 6 weeks. When compared to low-fat diet (LFD)-fed mice (LFD-mice), HFD-fed mice (HFD-mice) had impaired novel object recognition (NOR) after 1 week. After 3 weeks, HFD-mice had impaired NOR and object location recognition (OLR). Additionally, these mice displayed anxiety-like behavior by measure of both the open-field and elevated zero maze (EZM) testing. At 6 weeks, HFD-mice were comparable to LFD-mice in NOR, open-field and EZM performance but they remained impaired during OLR testing. Glyburide, a second-generation sulfonylurea for the treatment of type 2 diabetes, was chosen as a countermeasure based on previous data exhibiting its potential as an anxiolytic. Interestingly, a single dose of glyburide corrected deficiencies in NOR and mitigated anxiety-like behaviors in mice fed with HFD-diet for 3-weeks. Taken together these results indicate that a HFD negatively impacts a subset of hippocampal-independent behaviors relatively rapidly, but such behaviors normalize with age. In contrast, impairment of hippocampal-sensitive memory takes longer to develop but persists. Since single-dose glyburide restores brain function in 3-week-old HFD-mice, drugs that block ATP-sensitive K+ (KATP) channels may be of clinical relevance in the treatment of obesity-associated childhood cognitive issues and psychopathologies. PMID:27563288
Wang, Junhui; Zhu, Shenghua; Wang, Hongxing; He, Jue; Zhang, Yanbo; Adilijiang, Abulimiti; Zhang, Handi; Hartle, Kelly; Guo, Huining; Kong, Jiming; Huang, Qingjun; Li, Xin-Min
Previous studies have demonstrated that quetiapine (QTP) may have neuroprotective properties; however, the underlying mechanisms have not been fully elucidated. In this study, we identified a novel mechanism by which QTP increased the synthesis of ATP in astrocytes and protected GABAergic neurons from aging-induced death. In 12-month-old mice, QTP significantly improved cell number of GABAegic neurons in the cortex and ameliorated anxiety-like behaviors compared to control group. Complimentary in vitro studies showed that QTP had no direct effect on the survival of aging GABAergic neurons in culture. Astrocyte-conditioned medium (ACM) pretreated with QTP (ACMQTP) for 24 h effectively protected GABAergic neurons against aging-induced spontaneous cell death. It was also found that QTP boosted the synthesis of ATP from cultured astrocytes after 24 h of treatment, which might be responsible for the protective effects on neurons. Consistent with the above findings, a Rhodamine 123 test showed that ACMQTP, not QTP itself, was able to prevent the decrease in mitochondrial membrane potential in the aging neurons. For the first time, our study has provided evidence that astrocytes may be the conduit through which QTP is able to exert its neuroprotective effects on GABAergic neurons. The neuroprotective properties of quetiapine (QTP) have not been fully understood. Here, we identify a novel mechanism by which QTP increases the synthesis of ATP in astrocytes and protects GABAergic neurons from aging-induced death in a primary cell culture model. In 12-month-old mice, QTP significantly improves cell number of GABAegic neurons and ameliorates anxiety-like behaviors. Our study indicates that astrocytes may be the conduit through which QTP exerts its neuroprotective effects on GABAergic neurons.
Evren, Cuneyt; Umut, Gokhan; Evren, Bilge
The aim of the present study was to evaluate relationship of self-mutilative behaviour (SMB) with the severity of childhood trauma and adult attention-deficit/hyperactivity disorder (ADHD) symptoms in a sample of inpatients with alcohol use disorder (AUD). Participants included 188 inpatients with AUD. Participants were evaluated with the Self-mutilative Behaviour Questionnaire, the Childhood Trauma Questionnaire (CTQ-28) and the Adult ADD/ADHD DSM-IV Based Diagnostic Screening and Rating Scale (Adult ADHD Scale). Among inpatients with AUD those who have a history of SMB constituted the SMB group (n = 57, 30.3%), and those without a history of SMB constituted the group without SMB (n = 131, 69.7%). Risk of high ADHD risk was 2.5 times higher among those with SMB. Adult ADHD Scale and CTQ-28 scores were also higher in the group with SMB. In the first backward logistic regression model, the severity of ADHD symptoms predicted the presence of SMB, together with the severity of childhood trauma, whereas in the second model, physical neglect and inattentive (IN) dimension of ADHD predicted the presence of SMB. These findings suggest that the higher severity of physical neglect and adult IN dimension of ADHD may be related to SMB among inpatients with AUD.
Hartmann-Boyce, J; Johns, D J; Jebb, S A; Summerbell, C; Aveyard, P
This systematic review and meta-analysis of effectiveness trials comparing multicomponent behavioural weight management programmes with controls in overweight and obese adults set out to determine the effectiveness of these interventions implemented in routine practice. To be included, interventions must have been multicomponent, delivered by the therapists who would deliver the intervention in routine practice and in that same context, and must be widely available or feasible to implement with little additional infrastructure or staffing. Searches of electronic databases were conducted, and augmented by screening reference lists and contacting experts (November 2012). Data were extracted by two reviewers, with mean difference between intervention and control for 12-month change in weight, blood pressure, lipids and glucose calculated using baseline observation carried forward. Data were also extracted on adverse events, quality of life and mood measures. Although there were many published efficacy trials, only eight effectiveness trials met the inclusion criteria. Pooled results from five study arms providing access to commercial weight management programmes detected significant weight loss at 12 months (mean difference -2.22 kg, 95% confidence interval [CI] -2.90 to -1.54). Results from two arms of a study testing a commercial programme providing meal replacements also detected significant weight loss (mean difference -6.83 kg, 95% CI -8.39 to -5.26). In contrast, pooled results from five interventions delivered by primary care teams showed no evidence of an effect on weight (mean difference -0.45 kg, 95% CI -1.34 to 0.43). One study testing an interactive web-based intervention detected a significant effect in favour of the intervention at 12 months, but the study was judged to be at high risk of bias and the effect did not persist at 18 months. Few studies reported other outcomes, limiting comparisons between interventions. Few trials have examined the
Lerch, S; Dormann, C; Brandwein, C; Gass, P; Chourbaji, S
Early adverse experiences are known to influence the risk of developing psychiatric disorders later. To shed further light on the development of laboratory mice, we systematically examined the influence of a prenatal or postnatal olfactory stressor, namely unfamiliar male mouse faeces, presented to pregnant or nursing mouse dams. Maternal and offspring behaviours were then examined. Maternal behaviours relative to controls revealed changes in nest building by the pregnant dams exposed to the unfamiliar faeces. There were no differences among groups on pup retrieval or exploration by the dams. Behavioural phenotyping of male and female offspring as adults included measures of exploration, anxiety, social and depressive-like behaviours. Additionally, serum corticosterone was assessed as a marker of physiological stress response. Group differences were dependent on the sex of the adult offspring. Males raised by dams that were stressed during pregnancy presented elevated emotionality as indicated by increased numbers of faecal boluses in the open field paradigm. Consistent with the effects of prenatal stress on the males only the prenatally stressed females had higher body weights than their respective controls. Indeed, males in both experimental groups had higher circulating corticosterone levels. By contrast, female offspring of dams exposed to the olfactory stressor after parturition were more anxious in the O-maze as indicated by increased latencies in entering the exposed areas of the maze. These findings emphasize the necessity for researchers to consider the pre- and postnatal environments, even of mice with almost identical genetic backgrounds, in designing experiments and interpreting their data.
Investigating Low Adaptive Behaviour and Presence of the Triad of Impairments Characteristic of Autistic Spectrum Disorder as Indicators of Risk for Challenging Behaviour among Adults with Intellectual Disabilities
Felce, D.; Kerr, M.
Background: Identification of possible personal indicators of risk for challenging behaviour has generally been through association in cross-sectional prevalence studies, but few analyses have controlled for intercorrelation between potential risk factors. The aim was to investigate the extent to which gender, age, presence of the triad of…
Erickson, Zachary T.; Falkenberg, Erin A.; Metz, Gerlinde A. S.
The consumption of artificial food dye (AFD) during childhood and adolescence has been linked to behavioural changes, such as hyperactivity. It is possible that the vulnerability to AFDs is modified by prenatal stress. Common consequences of prenatal stress include hyperactivity, thus potentially leading to synergistic actions with AFDs. Here, we investigated the compounding effect of multigenerational prenatal stress (MPS) and AFD consumption on the development of hyperactivity and anxiety-related behaviours across the lifespan in male rats. MPS treatment involved a family history of four consecutive generations of prenatal stress (F4 generation). AFD treatment included a 4%-concentration of FD&C Red 40, FD&C Yellow 5, FD&C Yellow 6, and FD&C Blue 1 in the drinking water from postnatal days 22 to 50 to resemble juvenile and adolescent dietary exposure. Using several exploration tasks, animals were tested in motor activity and anxiety-like behaviours from adolescence to 13 months of age. MPS resulted in hyperactivity both early (50 days) and later in life (13 months), with normalized activity patterns at reproductive age. AFD consumption resulted in hyperactivity during consumption, which subsided following termination of treatment. Notably, both MPS and AFD promoted risk-taking behaviour in young adults (3 months). There were few synergistic effects between MPS and AFD in this study. The findings suggest that AFDs exert the most noticeable effects at the time of exposure. MPS, however, results in a characteristic lifespan profile of behavioural changes, indicating that development and aging represent particularly vulnerable periods in life during which a family history of prenatal stress may precipitate. PMID:24937660
Erickson, Zachary T; Falkenberg, Erin A; Metz, Gerlinde A S
The consumption of artificial food dye (AFD) during childhood and adolescence has been linked to behavioural changes, such as hyperactivity. It is possible that the vulnerability to AFDs is modified by prenatal stress. Common consequences of prenatal stress include hyperactivity, thus potentially leading to synergistic actions with AFDs. Here, we investigated the compounding effect of multigenerational prenatal stress (MPS) and AFD consumption on the development of hyperactivity and anxiety-related behaviours across the lifespan in male rats. MPS treatment involved a family history of four consecutive generations of prenatal stress (F4 generation). AFD treatment included a 4%-concentration of FD&C Red 40, FD&C Yellow 5, FD&C Yellow 6, and FD&C Blue 1 in the drinking water from postnatal days 22 to 50 to resemble juvenile and adolescent dietary exposure. Using several exploration tasks, animals were tested in motor activity and anxiety-like behaviours from adolescence to 13 months of age. MPS resulted in hyperactivity both early (50 days) and later in life (13 months), with normalized activity patterns at reproductive age. AFD consumption resulted in hyperactivity during consumption, which subsided following termination of treatment. Notably, both MPS and AFD promoted risk-taking behaviour in young adults (3 months). There were few synergistic effects between MPS and AFD in this study. The findings suggest that AFDs exert the most noticeable effects at the time of exposure. MPS, however, results in a characteristic lifespan profile of behavioural changes, indicating that development and aging represent particularly vulnerable periods in life during which a family history of prenatal stress may precipitate.
Nascimento, Marcus; Silva, Danielle; Ribeiro, Sandra; Nunes, Marco; Almeida, Marcos; Mendes-Netto, Raquel
The objective of the present study is to evaluate and compare the effect of a nutritional intervention between adolescent and adult. In a before and after quasi-experimental clinical study, 32 athletes (21 adults, age range 20–32 years; 11 adolescents, age range: 12–19 years) participated in a nutritional counselling consisting of four consultations separated by an interval of 45 to 60 days. The athlete’s eating behaviour, body composition and nutrition knowledge were evaluated at the beginning and at the end of the protocol. Both groups increased lean body mass and nutritional knowledge. Adolescents increased their mid-arm muscle circumference and improved meal frequency, and daily water intake. Athletes of both groups improved their ingestion of vegetables and fruits and decreased the ingestion of sweets and oils. Adolescents showed a higher prevalence of individuals that remained within or approached to the recommendations of sweets. This is the first study to evaluate and compare the effect of a nutritional intervention between adolescent and adult athletes body composition, eating behaviour and nutritional knowledge. The nutritional counselling has been effective in promoting beneficial changes on the athlete’s eating behaviour, nutritional knowledge and body composition, however, some healthy changes were only experienced by adolescents, especially in the frequency of meals and the intake of sweets. PMID:27618088
Elsinga, Jelte; Lizarazo, Erley F.; Vincenti, Maria F.; Schmidt, Masja; Velasco-Salas, Zoraida I.; Arias, Luzlexis; Bailey, Ajay; Tami, Adriana
Background Dengue in Venezuela is a major public health problem with an increasing incidence of severe cases. Early diagnosis and timely treatment influences the outcome of dengue illness, as delay in care-seeking is significantly associated with complications leading to severe dengue. We aimed to understand patterns of health seeking behaviour (HSB) in individuals exposed to high dengue incidence in order to improve early attendance to health centres. Methods Between September 2013 and February 2014 a cross-sectional household survey was performed in Maracay, Venezuela. Intended HSB of adults and children’s parents/guardians was assessed with respect to fever or suspected dengue. Data was collected through structured questionnaires from 105 individuals. Results Most individuals felt at risk of dengue and believed it could be a deadly disease. In the case of suspected dengue, the majority (60%) would choose to first seek medical help versus first treating at home, in contrast to 11% in the case of fever. Amongst those who decided to visit a doctor, a suspected dengue infection would prompt them to search medical help earlier than if having only fever (p<0.001). Multivariate analysis modelling showed that the independent factors associated with the intention to firstly visit a doctor versus treating at home in the case of dengue were feeling at risk (OR = 3.29; p = 0.042) and being an adult (as opposed to caring for a child as a parent/guardian; OR = 3.33, p = 0.021), while having had a previous dengue infection (OR = 0.29; p = 0.031) and living in the neighbourhood Caña de Azúcar (OR = 0.28, p = 0.038) were negatively associated with seeking medical care as their first action. Conclusion Knowledge of HSB related to dengue is scarce in the Americas, our study attempts to contribute to a better understanding of HSB in this region. Improving early dengue disease recognition and awareness may enhance prompt attendance to medical care in affected populations and
Badland, Hannah M.; Oliver, Melody; Kearns, Robin A.; Mavoa, Suzanne; Witten, Karen; Duncan, Mitch J.; Batty, G. David
Although the neighbourhoods and health field is well established, the relationships between neighbourhood selection, neighbourhood preference, work-related travel behaviours, and transport infrastructure have not been fully explored. It is likely that understanding these complex relationships more fully will inform urban policy development, and planning for neighbourhoods that support health behaviours. Accordingly, the objective of this study was to identify associations between these variables in a sample of employed adults. Self-reported demographic, work-related transport behaviours, and neighbourhood preference data were collected from 1616 employed adults recruited from 48 neighbourhoods located across four New Zealand cities. Data were collected between April 2008 and September 2010. Neighbourhood built environment measures were generated using geographical information systems. Findings demonstrated that more people preferred to live in urban (more walkable), rather than suburban (less walkable) settings. Those living in more suburban neighbourhoods had significantly longer work commute distances and lower density of public transport stops available within the neighbourhood when compared with those who lived in more urban neighbourhoods. Those preferring a suburban style neighbourhood commuted approximately 1.5 km further to work when compared with participants preferring urban settings. Respondents who preferred a suburban style neighbourhood were less likely to take public or active transport to/from work when compared with those who preferred an urban style setting, regardless of the neighbourhood type in which they resided. Although it is unlikely that constructing more walkable environments will result in work-related travel behaviour change for all, providing additional highly walkable environments will help satisfy the demand for these settings, reinforce positive health behaviours, and support those amenable to change to engage in higher levels of
Badland, Hannah M; Oliver, Melody; Kearns, Robin A; Mavoa, Suzanne; Witten, Karen; Duncan, Mitch J; Batty, G David
Although the neighbourhoods and health field is well established, the relationships between neighbourhood selection, neighbourhood preference, work-related travel behaviours, and transport infrastructure have not been fully explored. It is likely that understanding these complex relationships more fully will inform urban policy development, and planning for neighbourhoods that support health behaviours. Accordingly, the objective of this study was to identify associations between these variables in a sample of employed adults. Self-reported demographic, work-related transport behaviours, and neighbourhood preference data were collected from 1616 employed adults recruited from 48 neighbourhoods located across four New Zealand cities. Data were collected between April 2008 and September 2010. Neighbourhood built environment measures were generated using geographical information systems. Findings demonstrated that more people preferred to live in urban (more walkable), rather than suburban (less walkable) settings. Those living in more suburban neighbourhoods had significantly longer work commute distances and lower density of public transport stops available within the neighbourhood when compared with those who lived in more urban neighbourhoods. Those preferring a suburban style neighbourhood commuted approximately 1.5 km further to work when compared with participants preferring urban settings. Respondents who preferred a suburban style neighbourhood were less likely to take public or active transport to/from work when compared with those who preferred an urban style setting, regardless of the neighbourhood type in which they resided. Although it is unlikely that constructing more walkable environments will result in work-related travel behaviour change for all, providing additional highly walkable environments will help satisfy the demand for these settings, reinforce positive health behaviours, and support those amenable to change to engage in higher levels of
Background: There is a considerable body of evidence to suggest that behavioural activation for depression is an equally effective but less complex treatment than cognitive behavioural therapy. It may therefore be more suitable for those who are cognitively impaired (i.e. early-stage dementia or mild cognitive impairment) or have a learning…
Kalsy, Sunny; Heath, Rebecca; Adams, Dawn; Oliver, Chris
Background: Whereas there is a knowledge base on staff attributions of challenging behaviour, there has been little research on the effects of training, type of behaviour and biological context on staff attributions of controllability in the context of people with intellectual disabilities and dementia. Methods: A mixed design was used to…
Isbel, Luke; Prokopuk, Lexie; Wu, Haoyu; Daxinger, Lucia; Oey, Harald; Spurling, Alex; Lawther, Adam J; Hale, Matthew W; Whitelaw, Emma
We previously identified Wiz in a mouse screen for epigenetic modifiers. Due to its known association with G9a/GLP, Wiz is generally considered a transcriptional repressor. Here, we provide evidence that it may also function as a transcriptional activator. Wiz levels are high in the brain, but its function and direct targets are unknown. ChIP-seq was performed in adult cerebellum and Wiz peaks were found at promoters and transcription factor CTCF binding sites. RNA-seq in Wiz mutant mice identified genes differentially regulated in adult cerebellum and embryonic brain. In embryonic brain most decreased in expression and included clustered protocadherin genes. These also decreased in adult cerebellum and showed strong Wiz ChIP-seq enrichment. Because a precise pattern of protocadherin gene expression is required for neuronal development, behavioural tests were carried out on mutant mice, revealing an anxiety-like phenotype. This is the first evidence of a role for Wiz in neural function. DOI: http://dx.doi.org/10.7554/eLife.15082.001 PMID:27410475
Viberg, Henrik; Fredriksson, Anders; Eriksson, Per
Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice. Flame retardants are used to suppress or inhibit combustion processes in an effort to reduce the risk of fire. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), are present and increasing in the environment and in human milk. The present study shows that neonatal exposure to 2,2',4,4',5,5'-hexaBDE (PBDE 153), a PBDE persistent both in environment and in human milk, can induce developmental neurotoxic effects, such as changes in spontaneous behaviour (hyperactivity), impairments in learning and memory, and reduced amounts of nicotinic receptors, effects that get worse with age. Neonatal NMRI male mice were orally exposed on day 10 to 0.45, 0.9, or 9.0 mg of PBDE 153/kg of body weight. Spontaneous behaviour (locomotion, rearing, and total activity) was observed in 2-, 4-, and 6-month-old mice, Morris water maze at an age of 6 months. The behaviour tests showed that the effects were dose-response and time-response related. Animals showing defects in learning and memory also showed significantly reduced amounts of nicotinic receptors in hippocampus, using alpha-bungarotoxin binding assay. The observed developmental neurotoxic effects seen for PBDE 153 are similar to those seen for PBDE 99 and for certain PCBs. Furthermore, PBDEs appear to as potent as the PCBs.
Garg, Ruchika; Kumar, Anil
Sleep is an essential physiological process for maintaining physical, mental, and emotional health. Sleep deprivation and associated disorders like depression and anxiety are one of the major problems now-days. The present study was designed to explore the neuroprotecitve effect of citalopram and desipramine on 72 hr sleep deprivation-induced behavioral alterations and oxidative damage in mice. Various behavioral tests (plus maze, zero maze, mirror chamber, actophotometer), body weight followed by oxidative parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were assessed. Treatment with citalopram (5 and 10 mg/kg, ip) and desipramine (10 and 20 mg/kg, ip) for 5 days significantly improved locomotor activity, anti-anxiety like behavior in all paradigms tasks (mirror chamber, plus maze, zero maze) as compared to control (72 hr sleep-deprived). Biochemically, citalopram and desipramine treatment significantly restored depleted reduced glutathione, catalase activity, attenuated raised lipid peroxidation and nitrite level as compared to control (72 hr sleep-deprived) animals. Results of present study suggest that citalopram (5 and 10mg/kg, ip) and desipramine (10 and 20 mg/kg, ip) have neuroprotective effect against sleep deprivation-induced behavior alteration and oxidative damage in mice.
Vanderhaven, M W; Cornish, J L; Staples, L G
Increasing evidence suggests that the orexin system is involved in modulating anxiety, and we have recently shown that cat odor-induced anxiety in rats is attenuated by the orexin receptor antagonist SB-334867. In the current experiment, c-Fos expression was used to map changes in neuronal activation following SB-334867 administration in the cat odor anxiety model. Male Wistar rats were exposed to cat odor with or without SB-334867 pre-treatment (10 mg/kg, i.p.). A naïve control group not exposed to cat odor was also used. Following cat odor exposure, brains were processed for c-Fos expression. Vehicle-treated rats showed an increase in anxiety-like behaviors (increased hiding and decreased approach toward the cat odor), and increased c-Fos expression in the posteroventral medial amygdala (MePV), paraventricular hypothalamus (PVN) and dorsal premammillary nucleus (PMd). In rats pretreated with SB-334867, approach scores increased and c-Fos expression decreased in the PVN and PMd. These results provide both behavioral and neuroanatomical evidence for the attenuation of cat odor-induced anxiety in rats via the orexin system.
Paez-Martinez, Nayeli; Flores-Serrano, Zoraida; Ortiz-Lopez, Leonardo; Ramirez-Rodriguez, Gerardo
Toluene misuse is a health problem worldwide with broad effects at the level of the central nervous system; however, therapeutic alternatives for inhalant abusers are limited. Chronic use of volatile substances is associated with different neurological and cognitive alterations, being anxiety a psychiatric condition with high prevalence. At cellular level toluene reduces neurogenesis and induces neuronal death. On the other hand, environmental enrichment has demonstrated to produce positive effects at behavioral and neuronal levels. Thus, the aim of the present work was to model alterations occasioned after repeated exposure to toluene (anxiety, reduction in neurogenesis - measured as doublecortin-labeled cells - and neuronal death). Subsequently, the influence of environmental enrichment on these effects was evaluated. Adolescent mice were exposed to toluene vapors from 1 to 4 weeks. Effects on anxiety were evaluated with the burying behavior test, whereas neurogenesis and hippocampal cell death were analyzed with immunohistochemistry, using anti-doublecortin or anti-active-Caspase-3 antibodies, respectively. Results showed that chronic toluene exposure increased anxiety in the burying behavior test; additionally, toluene decreased neurogenesis and enhanced neuronal death. Environmental enrichment (EE) enhanced the anxiety like response in air-exposed mice but did not modify the toluene anxiety response. Additionally, EE enhanced neurogenesis in toluene-pretreated animals at the same level to that found in animals unexposed to toluene and decreased neuronal death. Overall, the present study showed that environmental enrichment positively impacts some effects produced by repeated exposure to toluene.
Liu, Fang-Fang; Yang, Lin-Dong; Sun, Xiao-Ru; Zhang, Hui; Pan, Wei; Wang, Xing-Ming; Yang, Jian-Jun; Ji, Mu-Huo; Yuan, Hong-Mei
Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, yet the precise mechanisms underlying PTSD remains largely to be determined. Using an animal model of PTSD induced by a single prolonged stress (SPS), we assessed the role of hippocampal nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and parvalbumin (PV) interneurons in the development of PTSD symptoms. In the present study, behavioral tests were performed by the open field (day 13 after SPS) and fear conditioning tests (days 13 and 14 after SPS). For the interventional study, rats were chronically treated with a NADPH oxidase inhibitor apocynin either by early or delayed administration. The levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, IL-10, malondialdehyde, superoxide dismutase, NOX2, 4-hydroxynonenal, and PV in the hippocampus were measured at the indicated time points. In the present study, we showed that SPS rats displayed anxiety-like and enhanced fear learning behavior, which was accompanied by the increased expressions of malondialdehyde, IL-6, NOX2, 4-hydroxynonenal, and decreased PV expression. Notably, early but not delayed treatment with apocynin reversed all these abnormalities after SPS. In conclusion, our results provided evidence that NOX2 activation in the hippocampus, at least in part, contributes to oxidative stress and neuroinflammation, which further results in PV interneuron loss and consequent PTSD symptoms in a rat model of PTSD induced by SPS.
Park, Subin; Cheong, Jae Hoon; Cho, Soo-Churl; Kim, Jae-Won; Shin, Min-Sup; Yoo, Hee Jeong; Han, Doug Hyun; Kim, Bung-Nyun
The authors aimed to study the effects of postnatal exposure to phthalate on anxiety-like behavior in mice and anxiety proneness in children. Male Imprinting Control Region (ICR) mice aged 4 weeks were administered 20 to 540 mg/kg of di-(2-ethylhexyl) phthalate (DEHP) or vehicle and assessed in the Open Field Test. A group of 277 children aged 8-11 years (150 males) was recruited from South Korea. A cross-sectional examination of urinary DEHP and dibutylphthalate metabolite concentrations was conducted, and the children were scored on the Trait Anxiety Inventory for Children (TAIC). DEHP metabolite concentrations in the urine were significantly and negatively correlated with TAIC scores in the female population but not in the male population. There were no significant group differences in the percentage of distance moved or time spent in the central area in male mice treated with DEHP or vehicle. Our results suggest a sex-dependent effect of DEHP on anxiety proneness in childhood.
Xiao, Zhaoyang; Jaiswal, Manoj; Deng, Pan-Yue; Matsui, Toshimitsu; Shin, Hee-Sup; Porter, James E.; Lei, Saobo
Whereas cholecystokinin (CCK) has long been known to exert anxiogenic effects in both animal anxiety models and humans, the underlying cellular and molecular mechanisms are ill-defined. CCK interacts with CCK-1 and CCK-2 receptors resulting in up-regulation of phospholipase C (PLC) and protein kinase C (PKC). However, the roles of PLC and PKC in CCK-mediated anxiogenic effects have not been determined. We have shown previously that CCK facilitates glutamate release in the hippocampus especially at the synapses formed by the perforant path and dentate gyrus granule cells via activations of PLC and PKC. Here we further demonstrated that CCK enhanced NMDA receptor function in dentate gyrus granule cells via activation of PLC and PKC pathway. At the single-channel level, CCK increased NMDA single-channel open probability and mean open time, reduced the mean close time and had no effects on the conductance of NMDA channels. Because elevation of glutamatergic functions results in anxiety, we explored the roles of PLC and PKC in CCK-induced anxiogenic actions using the Vogel Conflict Test (VCT). Our results from both pharmacological approach and knockout mice demonstrated that microinjection of CCK into the dentate gyrus concentration-dependently increased anxiety-like behavior via activation of PLC and PKC. Our results provide a novel unidentified signaling mechanism whereby CCK increases anxiety. PMID:22072552
Ruffault, Alexis; Czernichow, Sébastien; Hagger, Martin S; Ferrand, Margot; Erichot, Nelly; Carette, Claire; Boujut, Emilie; Flahault, Cécile
The aim of this study was to conduct a comprehensive quantitative synthesis of the effects of mindfulness training interventions on weight-loss and health behaviours in adults with overweight and obesity using meta-analytic techniques. Studies included in the analysis (k=12) were randomised controlled trials investigating the effects of any form of mindfulness training on weight loss, impulsive eating, binge eating, or physical activity participation in adults with overweight and obesity. Random effects meta-analysis revealed that mindfulness training had no significant effect on weight loss, but an overall negative effect on impulsive eating (d=-1.13) and binge eating (d=-.90), and a positive effect on physical activity levels (d=.42). Meta-regression analysis showed that methodological features of included studies accounted for 100% of statistical heterogeneity of the effects of mindfulness training on weight loss (R(2)=1,00). Among methodological features, the only significant predictor of weight loss was follow-up distance from post-intervention (β=1.18; p<.05), suggesting that the longer follow-up distances were associated with greater weight loss. Results suggest that mindfulness training has short-term benefits on health-related behaviours. Future studies should explore the effectiveness of mindfulness training on long-term post-intervention weight loss in adults with overweight and obesity.
Campillo, Cristina; Herrera, Gerardo; Remírez de Ganuza, Conchi; Cuesta, José L; Abellán, Raquel; Campos, Arturo; Navarro, Ignacio; Sevilla, Javier; Pardo, Carlos; Amati, Fabián
Deficits in the perception of time and processing of changes across time are commonly observed in individuals with autism. This pilot study evaluated the efficacy of the use of the software tool Tic-Tac, designed to make time visual, in three adults with autism and learning difficulties. This research focused on applying the tool in waiting situations where the participants exhibited anxiety-related behaviour. The intervention followed a baseline and intervention (AB) design, and a partial interval recording procedure was used to code the presence of stereotypes, nervous utterances, wandering or other examples of nervousness during the selected waiting situations. The results showed that the use of Tic-Tac resulted in lower levels of anxiety-related behaviour in all three participants, compared to the baseline, suggesting that this software may be an effective technology for helping people with autism with organisation and predictability during waiting periods. The results are discussed in terms of limitations and implications for further study.
Davies, Bronwen; Frude, Neil; Jenkins, Rosemary
This review questions whether a relationship exists between emotional recognition ability and challenging behaviour in people with an intellectual disability. A search was completed of a number of databases to identify relevant articles, and these were then evaluated against defined criteria. Eight articles were reviewed and their aims, study methodology, samples, measurement tools and findings are discussed and evaluated. Overall, studies found no significant deficit in the emotional recognition abilities of those with challenging behaviour when they were asked to identify the emotions of others. Two areas for further investigation were identified. Firstly, to ascertain whether a bias for identifying anger or sadness is found in those with challenging behaviour, and secondly, to understand the role of context in recognition of emotions and the degree to which this is different in those who present with challenging behaviour. A critique relating to the research is provided and suggested clinical and research implications are put forward.
The Development and Utility of a Program Theory: Lessons from an Evaluation of a Reputed Exemplary Residential Support Service for Adults with Intellectual Disability and Severe Challenging Behaviour in Victoria, Australia
Clement, Tim; Bigby, Christine
Background: Adults with severe challenging behaviour can achieve good "quality of life" outcomes in small supported accommodation services. Yet, the research indicates that they typically experience poorer outcomes than other adults with intellectual disability. This raises questions about the degree to which research has informed…
Walf, AA; Koonce, CJ; Frye, CA
Studies in people and animal models suggest that depression is influenced by natural, fluctuations in the levels of 17β-oestradiol (E2), as well as administration of E2-based therapies, such as selective oestrogen receptor modulators (SERMs). Elucidating the effects and mechanisms of E2 is important to improve future E2-based therapeutics. An important question is whether effects of E2 or SERMs for mood regulation act at the α or β isoform of the oestrogen receptor (ER) because some of the unwanted trophic effects of E2-based therapies may involve actions at ERα, rather than ERβ. In the present study, whether there are sex differences in depression-like behaviour of adult mice (experiment 1), and the effects of natural fluctuations in E2 (experiment 2), or administration of E2 or a SERM that has higher affinity for ERβ than for ERα (diarylpropionitrile; DPN) to ovariectomised (experiment 3) wildtype and ERβ knockout (βERKO) mice were investigated. Results of this study supported our hypotheses that: there would be sex differences favouring males for depression-like behaviour and endogenous increases in, or exogenous administration of, E2 or administration of an ERβ SERM would decrease depression-like behaviour in wildtype, but not βERKO, mice. In experiment 1, adult male mice spent less time immobile in the forced swim test (i.e., showed less depression-like behaviour) compared with female mice. In experiment 2, pro-oestrous (higher circulating E2 levels), compared with dioestrous (lower circulating E2 levels), mice had reduced immobility in the forced swim test; this effect was not observed in βERKO mice. In experiment 3, administration of E2 or DPN to ovariectomised wildtype, but not βERKO, mice decreased immobility compared with vehicle administration, these data suggest that ERβ may be required for some of the anti–depressant-like effects of E2. PMID:18562442
Imam, A; Ajao, M S; Akinola, O B; Ajibola, M I; Ibrahim, A; Amin, A; Abdulmajeed, W I; Lawal, Z A; Ali-Oluwafuyi, A
The most abused illicit drug in both the developing and the developed world is Cannabis disposing users to varying forms of personality disorders. However, the effects of cannabis on cortico-hippocampal architecture and cognitive behaviours still remain elusive. The present study investigated the neuro-cognitive implications of oral cannabis use in rats. Eighteen adult Wistar rats were randomly grouped to three. Saline was administered to the control rats, cannabis (20 mg/kg) to the experimental group I, while Scopolamine (1 mg/kg. ip) was administered to the last group as a standard measure for the cannabis induced cognitive impairment. All treatments lasted for seven consecutive days. Open Field Test (OFT) was used to assess locomotor activities, Elevated Plus Maze (EPM) for anxiety-like behaviour, and Y maze paradigm for spatial memory and data subjected to ANOVA and T test respectively. Thereafter, rats were sacrificed and brains removed for histopathological studies. Cannabis significantly reduced rearing frequencies in the OFT and EPM, and increased freezing period in the OFT. It also reduced percentage alternation similar to scopolamine in the Y maze, and these effects were coupled with alterations in the cortico-hippocampal neuronal architectures. These results point to the detrimental impacts of cannabis on cortico-hippocampal neuronal architecture and morphology, and consequently cognitive deficits.
Onakomaiya, Marie M; Porter, Donna M; Oberlander, Joseph G; Henderson, Leslie P
Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala.
Blasio, Angelo; Rice, Kenner C; Sabino, Valentina; Cottone, Pietro
The prevalence of eating disorders and obesity in Western societies is epidemic and increasing in severity. Preclinical research focused on the development of animal models which can mimic the maladaptive patterns of food intake observed in certain forms of eating disorders and obesity. This study was aimed at characterizing a recently established model of palatable diet alternation in female rats. For this purpose, females rats were fed either continuously with a regular chow diet (Chow/Chow) or intermittently with a regular chow diet for 2 days and a palatable, high-sucrose diet for 1 day (Chow/Palatable). Following diet cycling, rats were administered rimonabant (0, 0.3, 1, 3 mg/kg i.p.) during access to either palatable diet or chow diet and were assessed for food intake and body weight. Finally, rats were pretreated with rimonabant (0 – 3 mg/kg, i.p.) and tested in the elevated plus maze during withdrawal from the palatable diet. Female rats with alternating access to palatable food cycled their intake, overeating during access to the palatable diet, and under-eating upon returning to the regular chow diet. Rimonabant treatment resulted in increased chow hypophagia and anxiety-like behavior in Chow/Palatable rats. No effect of drug treatment was observed on the compulsive eating of palatable food in the diet cycled rats. The results of this study suggest that withdrawal from alternating access to the palatable diet makes individuals vulnerable to the anxiogenic effects of rimonabant and provide etiological factors potentially responsible for the emergence of severe psychiatric side-effects following rimonabant treatment in obese patients. PMID:25011007
Blasio, Angelo; Rice, Kenner C; Sabino, Valentina; Cottone, Pietro
The prevalence of eating disorders and obesity in western societies is epidemic and increasing in severity. Preclinical research has focused on the development of animal models that can mimic the maladaptive patterns of food intake observed in certain forms of eating disorders and obesity. This study was aimed at characterizing a recently established model of palatable diet alternation in female rats. For this purpose, females rats were fed either continuously with a regular chow diet (Chow/Chow) or intermittently with a regular chow diet for 2 days and a palatable, high-sucrose diet for 1 day (Chow/Palatable). Following diet cycling, rats were administered rimonabant (0, 0.3, 1, 3 mg/kg intraperitoneally) during access to either palatable diet or chow diet and were assessed for food intake and body weight. Finally, rats were pretreated with rimonabant (0, 3 mg/kg, intraperitoneally) and tested in the elevated plus maze during withdrawal from the palatable diet. Female rats with alternating access to palatable food cycled their intake, overeating during access to the palatable diet and undereating upon returning to the regular chow diet. Rimonabant treatment resulted in increased chow hypophagia and anxiety-like behavior in Chow/Palatable rats. No effect of drug treatment was observed on the compulsive eating of palatable food in the diet-cycled rats. The results of this study suggest that withdrawal from alternating access to the palatable diet makes individuals vulnerable to the anxiogenic effects of rimonabant and provides etiological factors potentially responsible for the emergence of severe psychiatric side-effects following rimonabant treatment in obese patients.
Reis, F M C V; Pestana-Oliveira, N; Leite, C M; Lima, F B; Brandão, M L; Graeff, F G; Del-Ben, C M; Anselmo-Franci, J A
Perimenopause, a transition period that precedes menopause, is characterized by neuroendocrine, metabolic and behavioral changes, and is associated with increased vulnerability to affective disorders. The decrease in ovarian follicles during perimenopause contributes to a dynamic and complex hormonal milieu that is not yet well characterized. In rodents, 4-vinylcyclohexene diepoxide (VCD) induces a gradual depletion of ovarian follicles, modeling the transition to menopause in women. This study was aimed to investigate, in VCD-treated rats, the hormonal status and the behavior in the elevated plus-maze (EPM), a widely used test to assess anxiety-like behavior. From the postnatal day 28, rats were treated with VCD or vehicle for 15 days. At 80±5 days after the beginning of treatment the experiments were performed at proestrus and diestrus. In the first experiment rats were decapitated, ovary was collected and blood samples were taken for estradiol, progesterone, follicle stimulant hormone (FSH), testosterone, dihydrotestosterone (DHT) and corticosterone measurements. In the second experiment, rats were subjected to the EPM for 5 min, and behavioral categories recorded. Administration of VCD induced follicular depletion as well as an increase of the number of atretic follicles demonstrating the treatment efficacy. The transitional follicular depletion was accompanied by lower progesterone, testosterone and DHT with no changes in the FSH, estradiol and corticosterone plasma levels. On the EPM, rats showed decreased open arm exploration and increased risk assessment behavior, indicating increased anxiety. These findings show that administration of VCD to induce ovarian failure results in endocrine and anxiety-related changes that are similar to the symptoms exhibited by women during menopause transition. Thus, this model seems to be promising in the study of perimenopause-related changes.
Ladrón de Guevara-Miranda, David; Pavón, Francisco J; Serrano, Antonia; Rivera, Patricia; Estivill-Torrús, Guillermo; Suárez, Juan; Rodríguez de Fonseca, Fernando; Santín, Luis J; Castilla-Ortega, Estela
The identification of behavioral traits that could predict an individual's susceptibility to engage in cocaine addiction is relevant for understanding and preventing this disorder, but investigations of cocaine addicts rarely allow us to determinate whether their behavioral attributes are a cause or a consequence of drug use. To study the behaviors that predict cocaine vulnerability, male C57BL/6J mice were examined in a battery of tests (the elevated plus maze, hole-board, novelty preference in the Y-Maze, episodic-like object recognition and forced swimming) prior to training in a cocaine-conditioned place preference (CPP) paradigm to assess the reinforcing value of the drug. In a second study, the anatomical basis of high and low CPP in the mouse brain was investigated by studying the number of neurons (neuronal nuclei-positive) in two addiction-related limbic regions (the medial prefrontal cortex and the basolateral amygdala) and the number of dopaminergic neurons (tyrosine hydroxylase-positive) in the ventral tegmental area by immunohistochemistry and stereology. Correlational analyses revealed that CPP behavior was successfully predicted by anxiety-like measures in the elevated plus maze (i.e., the more anxious mice showed more preference for the cocaine-paired compartment) but not by the other behaviors analyzed. In addition, increased numbers of neurons were found in the basolateral amygdala of the high CPP mice, a key brain center for anxiety and fear responses. The results support the theory that anxiety is a relevant factor for cocaine vulnerability, and the basolateral amygdala is a potential neurobiological substrate where both anxiety and cocaine vulnerability could overlap.
Onakomaiya, Marie M.; Porter, Donna M.; Oberlander, Joseph G.; Henderson, Leslie P.
Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala. PMID:24768711
Zhang, Wenping; Tian, Fengjie; Zheng, Jinping; Li, Senlin; Qiang, Mei
Background Recently, an increasing number of human and animal studies have reported that exposure to benzo(a)pyrene (BaP) induces neurological abnormalities and is also associated with adverse effects, such as tumor formation, immunosuppression, teratogenicity, and hormonal disorders. However, the exact mechanisms underlying BaP-induced impairment of neurological function remain unclear. The aim of this study was to examine the regulating mechanisms underlying the impact of chronic BaP exposure on neurobehavioral performance. Methods C57BL mice received either BaP in different doses (1.0, 2.5, 6.25 mg/kg) or olive oil twice a week for 90 days. Memory and emotional behaviors were evaluated using Y-maze and open-field tests, respectively. Furthermore, levels of mRNA expression were measured by using qPCR, and DNA methylation of NMDA receptor 2B subunit (NR2B) was examined using bisulfate pyrosequencing in the prefrontal cortex and hippocampus. Results Compared to controls, mice that received BaP (2.5, 6.25 mg/kg) showed deficits in short-term memory and an anxiety-like behavior. These behavioral alterations were associated with a down-regulation of the NR2B gene and a concomitant increase in the level of DNA methylation in the NR2B promoter in the two brain regions. Conclusions Chronic BaP exposure induces an increase in DNA methylation in the NR2B gene promoter and down-regulates NR2B expression, which may contribute to its neurotoxic effects on behavioral performance. The results suggest that NR2B vulnerability represents a target for environmental toxicants in the brain. PMID:26901155
Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne
Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This "preliminary" randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive…
Sumner-Rooney, Lauren H.; Sigwart, Julia D.
The discovery of a sensory organ, the Schwabe organ, was recently reported as a unifying feature of chitons in the order Lepidopleurida. It is a patch of pigmented tissue located on the roof of the pallial cavity, beneath the velum on either side of the mouth. The epithelium is densely innervated and contains two types of potential sensory cells. As the function of the Schwabe organ remains unknown, we have taken a cross-disciplinary approach, using anatomical, histological and behavioural techniques to understand it. In general, the pigmentation that characterises this sensory structure gradually fades after death; however, one particular concentrated pigment dot persists. This dot is positionally homologous to the larval eye in chiton trochophores, found in the same neuroanatomical location, and furthermore the metamorphic migration of the larval eye is ventral in species known to possess Schwabe organs. Here we report the presence of a discrete subsurface epithelial structure in the region of the Schwabe organ in Leptochiton asellus that histologically resembles the chiton larval eye. Behavioural experiments demonstrate that Leptochiton asellus with intact Schwabe organs actively avoid an upwelling light source, while Leptochiton asellus with surgically ablated Schwabe organs and a control species lacking the organ (members of the other extant order, Chitonida) do not (Kruskal-Wallis, H = 24.82, df = 3, p < 0.0001). We propose that the Schwabe organ represents the adult expression of the chiton larval eye, being retained and elaborated in adult lepidopleurans. PMID:26366861
Sumner-Rooney, Lauren H; Sigwart, Julia D
The discovery of a sensory organ, the Schwabe organ, was recently reported as a unifying feature of chitons in the order Lepidopleurida. It is a patch of pigmented tissue located on the roof of the pallial cavity, beneath the velum on either side of the mouth. The epithelium is densely innervated and contains two types of potential sensory cells. As the function of the Schwabe organ remains unknown, we have taken a cross-disciplinary approach, using anatomical, histological and behavioural techniques to understand it. In general, the pigmentation that characterises this sensory structure gradually fades after death; however, one particular concentrated pigment dot persists. This dot is positionally homologous to the larval eye in chiton trochophores, found in the same neuroanatomical location, and furthermore the metamorphic migration of the larval eye is ventral in species known to possess Schwabe organs. Here we report the presence of a discrete subsurface epithelial structure in the region of the Schwabe organ in Leptochiton asellus that histologically resembles the chiton larval eye. Behavioural experiments demonstrate that Leptochiton asellus with intact Schwabe organs actively avoid an upwelling light source, while Leptochiton asellus with surgically ablated Schwabe organs and a control species lacking the organ (members of the other extant order, Chitonida) do not (Kruskal-Wallis, H = 24.82, df = 3, p < 0.0001). We propose that the Schwabe organ represents the adult expression of the chiton larval eye, being retained and elaborated in adult lepidopleurans.
Dutheil, Sophie; Lacour, Michel; Tighilet, Brahim
Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of
Young, Susan; Emilsson, Brynjar; Sigurdsson, Jon Fridrik; Khondoker, Mizanur; Philipp-Wiegmann, Florence; Baldursson, Gisli; Olafsdottir, Halldora; Gudjonsson, Gisli
Studies assessing psychological treatment of attention deficit hyperactivity disorder (ADHD) in adults are increasingly reported. However, functional outcomes are often neglected in favour of symptom outcomes. We investigated functional outcomes in 95 adults with ADHD who were already treated with medication and randomized to receive treatment as usual (TAU/MED) or psychological treatment (CBT/MED) using a cognitive-behavioural programme, R&R2ADHD, which employs both group and individual modalities. RATE-S functional outcomes associated with ADHD symptoms, social functioning, emotional control and antisocial behaviour were given at baseline, end of treatment and three-month follow-up. The Total composite score of these scales is associated with life satisfaction. In addition, independent evaluator ratings of clinicians who were blind to treatment arm were obtained on the Clinical Global Impression scale at each time point. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater functional improvement on all scales. Post-group treatment effects were maintained at follow-up with the exception of emotional control and the Total composite scales, which continued to improve. The largest treatment effect was for the RATE-S Total composite scale, associated with life satisfaction. CGI significantly correlated with all outcomes except for social functioning scale at follow-up. The study provides further evidence for the effectiveness of R&R2ADHD and demonstrates the importance of measuring functional outcomes. The key mechanism associated with improved functional outcomes is likely to be behavioural control.
Protocol for a systematic review of telephone delivered psychosocial interventions on relapse prevention, adherence to psychiatric medication and health risk behaviours in adults with a psychotic disorder
Beck, Alison K; Baker, Amanda; Turner, Alyna; Haddock, Gillian; Kelly, Peter J; Berry, Katherine; Bucci, Sandra
Introduction The mental and physical health of individuals with a psychotic illness are typically poor. When adhered to, medication can reduce relapse. However, despite adherence, relapse remains common and functional outcomes often remain compromised. Compliance is also typically low. Cardiovascular-related morbidity and mortality is also elevated, along with several important modifiable health risk behaviours. Access to psychosocial interventions is therefore important, but currently limited. Telephone delivered interventions represent a promising solution, although further clarity is needed. Accordingly, we aim to provide an overview and critical analysis of the current state of evidence for telephone delivered psychosocial interventions targeting key health priorities in adults with a psychotic disorder, including (1) relapse, (2) adherence to psychiatric medication and/or (3) modifiable cardiovascular health risk behaviours. Methods and analysis Our methods are informed by published guidelines. The review is registered and any protocol amendments will be tracked. Ten electronic peer-reviewed and four grey literature databases have been identified. Preliminary searches have been conducted for literature on psychosocial telephone interventions targeting relapse, medication adherence and/or health risk behaviours in adults with a psychotic disorder. Articles classified as ‘evaluation’ will be assessed against standardised criteria and checked by an independent assessor. The searches will be re-run just before final analyses and further studies retrieved for inclusion. A narrative synthesis will be reported, structured around intervention type and content, population characteristics and outcomes. Where possible, ‘summary of findings’ tables will be generated for each comparison. For the primary outcome of each trial, when data are available, we will calculate a risk ratio and its 95% CI (dichotomous outcomes) and/or effect size according to Cohen's formula
Travis, Robert W.; Sturmey, Peter
Background: Previous studies of anger management in people with intellectual disability failed to control for the effects of the number of provocative stimuli presented and lacked direct measures of behaviour and treatment integrity data. Methods: This experiment systematically assessed and presented discriminative stimuli for aggressive…
Davies, Bronwen; Frude, Neil; Jenkins, Rosemary
This review questions whether a relationship exists between emotional recognition ability and challenging behaviour in people with an intellectual disability. A search was completed of a number of databases to identify relevant articles, and these were then evaluated against defined criteria. Eight articles were reviewed and their aims, study…
Oliver-Africano, P.; Dickens, S.; Ahmed, Z.; Bouras, N.; Cooray, S.; Deb, S.; Knapp, M.; Hare, M.; Meade, M.; Reece, B.; Bhaumik, S.; Harley, D.; Piachaud, J.; Regan, A.; Ade Thomas, D.; Karatela, S.; Rao, B.; Dzendrowskyj, T.; Lenotre, L.; Watson, J.; Tyrer, P.
Background: Aggressive challenging behaviour in people with intellectual disability (ID) is frequently treated with antipsychotic drugs, despite a limited evidence base. Method: A multi-centre randomised controlled trial was undertaken to investigate the efficacy, adverse effects and costs of two commonly prescribed antipsychotic drugs…
Gerber, F.; Bessero, S.; Robbiani, B.; Courvoisier, D. S.; Baud, M. A.; Traore, M.-C.; Blanco, P.; Giroud, M.; Carminati, G. Galli
Background: Owing to methodological issues, little research has been conducted to examine quality of life (QoL) as a treatment outcome in autism spectrum disorders (ASD) and intellectual disabilities (ID). This study was conducted to combine QoL measures and objective observations of challenging behaviours (CB) in order to evaluate changes over…
García-Villamisar, D.; Rojahn, J.
Background: Comorbid psychopathology and stress were considered possible mediators that may explain the relationship between some autistic traits and repetitive behaviours. The current study sought to examine the mediational effects of comorbid psychopathology, executive dysfunctions and stress in the relationship between some autistic traits and…
Campbell, Martin; Hogg, James
Background: Cognitive representations of challenging behaviour among staff may influence therapeutic outcomes. This study looked at how cognitive dimensions of Identity, Cause, Consequences, Emotional Reaction and Treatment/Control are affected by training. Materials and Methods: A theoretically derived questionnaire was used to measure the impact…
Hotulainen, Risto; Lappalainen, Kristiina
In a 15-year longitudinal study, a retrospective quasipanel design was chosen to detect developmental patterns related to the students' (N = 78) self-ratings. In 1999 (grade 9), the students who were rated as part of the risk group (n = 22) by using their kindergarten teachers' initial socio-emotional behaviour ratings that were done in 1989, were…
McNair, Louisa; Woodrow, Ceri; Hare, Dougal
Background: Government strategy indicates that individuals with learning disabilities should have access to adapted psychological therapies. Dialectical behaviour therapy (DBT) is recommended for the treatment of borderline personality disorder (BPD); however, there is little published research regarding whether it can be appropriately adapted for…
Sink, KS; Walker, DL; Yang, Y; Davis, M
Calcitonin gene-related peptide (CGRP) evokes anxiety-like responses when infused into the lateral ventricle of rats. Because the bed nucleus of the stria terminalis (BNST) lies immediately adjacent to the lateral ventricle, is rich in CGRP receptors, and has itself been implicated in anxiety, we evaluated the hypothesis that these effects are attributable to stimulation of CGRP receptors within the BNST itself. Bilateral intra-BNST, but not dorsal, CGRP infusions (0, 200, 400, 800 ng/side) dose-dependently enhanced startle amplitude, and produced an anxiety-like response on the elevated plus maze. Intra-BNST infusion of the CGRP antagonist, αCGRP8-37, blocked the effect of CGRP on startle, and also blocked startle potentiation produced by exposure to trimethylthiazoline (TMT – a component of fox feces that induces anxiety-like behavior in rats). Intra-BNST, but not dorsal, CGRP infusions also increased c-Fos immunoreactivity in a number of anxiety-related brain areas (central nucleus of the amygdala, locus coeruleus, ventrolateral septal nucleus, paraventricular hypothalamic nucleus, lateral hypothalamus, lateral parabrachial nucleus, dorsal raphe nucleus, and nucleus accumbens shell), all of which receive direct projections from the BNST. Together, the results indicate that the activation of BNST CGRP receptors is both necessary and sufficient for some anxiety responses and that these effects may be mediated by activation of a wider network of BNST efferent structures. If so, inhibition of CGRP receptors may be a clinically useful strategy for anxiety reduction. PMID:21289190
Colombo, Giancarlo; Lobina, Carla; Maccioni, Paola; Carai, Mauro A M; Lorrai, Irene; Zaru, Alessandro; Contini, Andrea; Mugnaini, Claudia; Corelli, Federico; Gessa, Gian Luigi
Recent research found that exposure of selectively bred, Sardinian alcohol-preferring (sP) rats to multiple alcohol concentrations (10%, 20%, and 30%, v/v), under the 4-bottle "alcohol vs. water" choice regimen, in daily 1-h drinking sessions with an unpredictable time schedule, promoted high intakes of alcohol (≥2 g/kg) when the drinking session occurred over the final hours of the dark phase of the light/dark cycle. The present study investigated whether these high intakes of alcohol (a) were associated with alterations in rats' emotional state (Experiment 1) and (b) were pharmacologically manipulable (Experiment 2). In both experiments, over a period of 12 days, sP rats were initially exposed daily to a 1-h drinking session during the dark phase; time of alcohol exposure was changed each day and was unpredictable to rats. The day after this 12-day drinking phase, rats were (a) exposed to the Social Interaction (SI) test at the 1st or 12th hour of the dark phase with no alcohol available (Experiment 1) or (b) treated with the positive allosteric modulator of the GABAB receptor, GS39783 (0, 25, 50, and 100 mg/kg, intragastrically [i.g.]), and exposed to a drinking session at the 12th hour of the dark phase (Experiment 2). In Experiment 1, rats exposed to the SI test during the 12th hour spent approximately 35% less time in "social" behaviors than rats exposed to the SI test during the 1st hour. No difference in "social" behaviors was observed between alcohol-naive sP rats exposed to the SI test at the 1st and 12th hour. In Experiment 2, all doses of GS39783 selectively reduced alcohol intake. These results suggest that (a) expectation of alcohol availability likely exacerbated the anxiety-like state of sP rats and (b) the GABAB receptor is part of the neural substrate underlying these exceptionally high intakes of alcohol in sP rats.
André, Caroline; Dinel, Anne-Laure; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie
Obesity is associated with a high prevalence of mood symptoms and cognitive dysfunctions that emerges as significant risk factors for important health complications such as cardiovascular diseases and type 2 diabetes. It is therefore important to identify the dynamic of development and the pathophysiological mechanisms underlying these neuropsychiatric symptoms. Obesity is also associated with peripheral low-grade inflammation and increased susceptibility to immune-mediated diseases. Excessive production of proinflammatory cytokines and the resulting activation of the brain tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been shown to promote neurobehavioral complications, particularly depression. In that context, questions arise about the impact of diet-induced obesity on the onset of neuropsychiatric alterations and the increased susceptibility to immune-mediated diseases displayed by obese patients, particularly through brain IDO activation. To answer these questions, we used C57Bl/6 mice exposed to standard diet or western diet (WD; consisting of palatable energy-dense food) since weaning and for 20 weeks. We then measured inflammatory and behavioral responses to a systemic immune challenge with lipopolysaccharide (LPS) in experimental conditions known to alter cognitive and emotional behaviors independently of any motor impairment. We first showed that in absence of LPS, 9 weeks of WD is sufficient to impair spatial recognition memory (in the Y-maze). On the other hand, 18 weeks of WD increased anxiety-like behavior (in the elevated plus-maze), but did not affect depressive-like behavior (in the tail-suspension and forced-swim tests). However, 20 weeks of WD altered LPS-induced depressive-like behavior compared to LPS-treated lean mice and exacerbated hippocampal and hypothalamic proinflammatory cytokine expression and brain IDO activation. Taken together, these results show that WD exposure alters cognition and anxiety in unstimulated
Colombo, Giancarlo; Lobina, Carla; Maccioni, Paola; Carai, Mauro A.M.; Lorrai, Irene; Zaru, Alessandro; Contini, Andrea; Mugnaini, Claudia; Corelli, Federico; Gessa, Gian Luigi
Recent research found that exposure of selectively bred, Sardinian alcohol-preferring (sP) rats to multiple alcohol concentrations (10%, 20%, and 30%, v/v), under the 4-bottle “alcohol vs. water” choice regimen, in daily 1-h drinking sessions with an unpredictable time schedule, promoted high intakes of alcohol (≥2 g/kg) when the drinking session occurred over the final hours of the dark phase of the light/dark cycle. The present study was aimed at investigating whether these high intakes of alcohol (a) were associated with alterations in rats’ emotional state (Experiment 1) and (b) were pharmacologically manipulable (Experiment 2). In both experiments, over a period of 12 days, sP rats were initially exposed daily to a1-h drinking session performed during the 12-h duration of the dark phase; time of alcohol exposure was changed each day and was unpredictable to rats. The day after this 12-day drinking phase, rats were (a) exposed to the Social Interaction (SI) test at the 1st or 12th hour of the dark phase with no alcohol available (Experiment 1) or (b) treated acutely with the positive allosteric modulator of the GABAB receptor, GS39783 (0, 25, 50, and 100 mg/kg, intragastrically [i.g.]), and exposed to a drinking session at the 12th hour of the dark phase (Experiment 2). In Experiment 1, rats exposed to the SI test during the 12th hour spent approximately 35% less time in “social” behaviors than rats exposed to the SI test during the 1st hour. No difference in “social” behaviors was observed between alcohol-naive sP rats exposed to the SI test at the 1st and 12th hour. In Experiment 2, all doses of GS39783 selectively reduced alcohol intake. These results suggest that (a) expectation of alcohol availability likely exacerbated the anxiety-like state of sP rats and (b) the GABAB receptor is part of the neural substrate underlying these exceptionally high intakes of alcohol in sP rats. PMID:26254964
Richter-Appelt, Hertha; Discher, Christine; Gedrose, Benjamin
The concept of intersexuality subsumes a wide variety of phenomena with very specific underlying causes. In all these cases, an untypical development takes place during the prenatal sex differentiation process becoming clinically manifest, either at, or soon after birth or at the time of puberty. It subsumes conditions in which biological sexual characteristics (e.g. chromosomal sex, gonadal sex, hormonal sex, morphological sex) differ from each other and one person cannot easily be assigned to one sex. One of the main goals of medical treatment of persons with intersex-syndroms is the development of a stable gender identity. Over the last few years, sex (and gender) assignment of persons with different forms of intersexuality has become a much discussed topic. An interesting--and very obviously observable--variable that was brought in connection with sex assignment is gender related childhood play behaviour. The purpose of the presented study is to examine 37 persons with different forms of intersexuality (disturbances of androgen biosynthesis, partial and complete androgen insensitivity, gonadal dysgenesis with 46,XY and congenital adrenal hyperplasia with 46,XX) with regard to gender identity and gender role behaviour in childhood. Not all subjects in the study group had developed a clear female or male gender identity. In contrast to previous studies, some persons with CAIS did not recall distinguished female childhood play behaviour and these persons did not show a clear female gender identity. In contrast to results from other studies, the CAH-affected girls in this study did not seem to recall masculinized behaviour. Further research is needed to guarantee better psychosexual development with good quality of life in individuals with intersexuality.
Götz, Alexander A; Stefanski, Volker
Exposure to prenatal stress can impair the behavioural and hormonal development in mammals. However, the consequences for the immune system are rarely investigated and there is only limited evidence that naturalistic prenatal stressors do also have the potential to affect the offspring. Thus, by using a social conflict model in female Long-Evans rats, we investigated the effects of prenatal social stress on several behavioural, hormonal and immunological parameters. Offspring from stressed and non-stressed pregnant females were housed in pairs after weaning, and tested at an age of 4-6 months. Prenatally stressed (PS) males were more active in the elevated plus-maze test as indicated by significantly more frequent entries into the open arms compared to prenatal control males (PC). In addition, PS males had significantly lower serum corticosterone concentrations under basal conditions as well as after ACTH-challenge. The basal number of total leukocytes was significantly lower in the PS group due to significantly lower lymphocyte counts. In particular, the CD4+ T-helper cell subset was affected. The lymphocyte proliferation to pokeweed mitogen was lower in PS males. Because some of the present findings do not correspond to previous studies using conventional stressors, we assume that the nature of the stressor plays an important role for pregnancy outcome and behaviour and physiology of the offspring in later life.
Gibula-Bruzda, Ewa; Marszalek-Grabska, Marta; Witkowska, Ewa; Izdebski, Jan; Kotlinska, Jolanta H
An analog of enkephalin, cyclo[N(ε),N(β)-carbonyl-D-Lys(2),Dap(5)] enkephalinamide (cUENK6), is predominantly a functional agonist of μ-opioid receptors (MOPr) and, to a lesser extent, of δ-opioid receptors (DOPr) in vitro. The aim of the present study was to determine whether cUENK6 could affect ethanol withdrawal-induced anxiety-like behavior in the elevated plus maze (EPM) test in rats. An anxiety-like effect of withdrawal was predicted to occur in the EPM test 24 h after the last ethanol administration (2 g/kg, intraperitoneally [i.p.]; 15% w/v once daily for 9 days). Ethanol withdrawal decreased the percent of time spent by rats in the open arms and the percent of open-arms entries. cUENK6 (0.25 nmol), given by intracerebroventricular (i.c.v.) injection, significantly reversed these anxiety-like effects of ethanol withdrawal and elevated the percent of time spent by rats in the open arms and the percent of open-arms entries. These effects of cUENK6 were significantly inhibited by the DOPr antagonist naltrindole (NTI) (5 nmol, i.c.v.), but not by the MOPr antagonist β-funaltrexamine (β-FNA) (5 nmol, i.c.v.). The preferential DOPr agonist [Leu(5)]-enkephalin (LeuEnk) (2.7 and 5.4 nmol, i.c.v.) and the MOPr agonist morphine (6.5 and 13 nmol, i.c.v.) reduced the anxiety-like effects of ethanol withdrawal. cUENK6 at the dose of 0.25 nmol did not disturb locomotor activity in the EPM, in contrast to cUENK6 at the dose of 0.5 nmol, and morphine at 6.5 and 13 nmol. However, similarly to LeuEnk, cUENK6 induced the anxiolytic-like effects in naïve rats. Thus, our study suggests that cUENK6 reduced ethanol withdrawal-induced anxiety-like behavior by activation of δ-opioid receptors rather than μ-opioid receptors.
Pawluski, Jodi L; Lieblich, Stephanie E; Galea, Liisa A M
In women, breastfeeding generally results in reductions in anxiety and increased positive mood. However, approximately 10-15% of women experience depressed mood and increased anxiety during the first year postpartum. Recent research has demonstrated that offspring-exposure is important for the reduction in behaviours related to depression and anxiety in the mother. It remains to be determined whether these effects are due to factors related to pregnancy and/or pup-exposure, are associated with the degree of maternal behaviour by the mother towards offspring, or persist after weaning. To address these questions the present study used four groups of female rats; primiparous, nulliparous, primip-no-pups (primiparous females with pups permanently removed), and sensitized females. Depressive- and anxiety-like behaviours were assessed 1 week after weaning/pup-exposure (4 weeks after birth for primip-no-pups animals) using the forced swim test for measures of depressive-like behaviour, and the open field test and elevated plus maze for measure of anxiety-like behaviour. Results demonstrate that primiparous females without pup-exposure have increased depressive-like, but not anxiety-like, behaviour compared to primiparous and sensitized females. In addition, kyphotic nursing by primiparous mothers was negatively related to behavioural measures of depression and anxiety. From this work it is clear that pup-exposure is important for reductions in depressive-like behaviour in parturient females. Further research is needed to determine the extent of these changes and the neural and hormonal correlates of these events.
Background A cancer diagnosis is 2.9 times more likely to occur during the adolescent and young adult years than in younger children. This spike in incidence coincides with a life stage characterised by psychological vulnerability as young people strive to attain numerous, critical developmental milestones. The distress young people experience after cancer treatment seriously jeopardises their ability to move into well-functioning adulthood. Methods/Design This article presents the protocol of the Recapture Life study, a phase II three-arm randomised controlled trial designed to evaluate the feasibility and efficacy of a new intervention in reducing distress and improving quality of life for adolescent and young adult cancer survivors. The novel intervention, “ReCaPTure LiFe” will be compared to a both a wait-list, and a peer-support group control. Ninety young people aged 15–25 years who have completed cancer treatment in the past 1–6 months will be recruited from hospitals around Australia. Those randomised to receive Recapture Life will participate in six, weekly, 90-minute online group sessions led by a psychologist, involving peer-discussion around cognitive-behavioural coping skills (including: behavioural activation, thought challenging, communication and assertiveness skills training, problem-solving and goal-setting). Participants randomised to the peer-support group control will receive non-directive peer support delivered in an identical manner. Participants will complete psychosocial measures at baseline, post-intervention, and 12-months post-intervention. The primary outcome will be quality of life. Secondary outcomes will include depression, anxiety, stress, family functioning, coping, and cancer-related identity. Discussion This article reviews the empirical rationale for using group-based, online cognitive-behavioural therapy in young people after cancer treatment. The potential challenges of delivering skills-based programs in an online
Background Interventions to promote physical activity have had limited success. One reason may be that inactive adults are unaware that their level of physical activity is inadequate and do not perceive a need to change their behaviour. We aimed to assess awareness of physical activity, defined as the agreement between self-rated and objective physical activity, and to investigate associations with sociodemographic, biological, behavioural, and psychological factors. Methods We conducted an exploratory, cross-sectional analysis of awareness of physical activity using baseline data collected from 453 participants of the Feedback, Awareness and Behaviour study (Cambridgeshire, UK). Self-rated physical activity was measured dichotomously by asking participants if they believed they were achieving the recommended level of physical activity. Responses were compared to objective physical activity, measured using a combined accelerometer and heart rate monitor (Actiheart®). Four awareness groups were created: overestimators, realistic inactives, underestimators, and realistic actives. Logistic regression was used to assess associations between awareness group and potential correlates. Results The mean (standard deviation) age of participants was 47.0 (6.9) years, 44.4% were male, and 65.1% were overweight (body mass index ≥ 25). Of the 258 (57.0%) who were objectively classified as inactive, 130 (50.4%) misperceived their physical activity by incorrectly stating that they were meeting the guidelines (overestimators). In a multivariable logistic regression model adjusted for age and sex, those with a lower body mass index (Odds Ratio (OR) = 0.95, 95% Confidence Interval (CI) = 0.90 to 1.00), higher physical activity energy expenditure (OR = 1.03, 95% CI = 1.00 to 1.06) and self-reported physical activity (OR = 1.13, 95% CI = 1.07 to 1.19), and lower intention to increase physical activity (OR = 0.69, 95% CI = 0.48 to 0.99) and
Brunton, Paula J; Donadio, Márcio V F; Russell, John A
We recently reported that male, but not female, offspring born to mothers exposed to social stress during late gestation show heightened anxiety-type behaviour in adulthood. The amygdala organises anxious behaviour, which involves actions of corticotropin-releasing hormone (CRH). CRH gene expression and/or its release are increased in the amygdala in prenatally stressed (PNS) rats. CRH type 1 receptor (CRH-R1) mediates actions of CRH and urocortin I to promote anxiety-like behaviour, whereas the CRH type 2 receptor (CRH-R2) may mediate anxiolytic actions, through actions of urocortins 2 and 3. Here, using quantitative in situ hybridisation, we investigated whether altered CRH receptor mRNA expression in the amygdaloid nuclei may explain the sex differences in anxiety behaviour in adult male and female PNS rats. CRH-R1 mRNA expression was significantly greater in the central amygdala and basolateral amygdala (BLA) in male PNS rats compared with controls, with no change in the basomedial amygdala (BMA) or medial amygdala (MeA). In PNS females, CRH-R1 mRNA expression was greater than controls only in the MeA. Conversely, CRH-R2 mRNA expression was significantly lower in the BMA of male PNS rats compared with controls, but greater in female PNS rats, with no change in the BLA or MeA in either sex. The ratio of CRH-R1:CRH-R2 mRNA in the amygdaloid nuclei was generally increased in PNS males, but not in the PNS females. In conclusion, sex differences in anxiety-type behaviour in PNS rats may be explained by differential mRNA expression for CRH-R1 (pro-anxiogenic) and CRH-R2 (pro-anxiolytic) in the amygdaloid complex.
Whitehouse, Richard M.; Tudway, Jeremy A.; Look, Roger; Kroese, Biza Stenfert
Background: Historically, adults with intellectual disabilities have had little access to individual psychotherapy. Over the last 20 years an increasing body of literature has described psychotherapy with this client group and reported methods for adapting traditional psychotherapeutic techniques. Method: The current review identified the…
Winters, Meghan; Voss, Christine; Ashe, Maureen C; Gutteridge, Kaitlyn; McKay, Heather; Sims-Gould, Joanie
Mobility-the ability to move about in one's neighbourhood and maintain independence-is essential for older adults' wellbeing. Neighbourhood environments support or hinder mobility especially as health declines and physical vulnerability increases with age. Linkages between mobility and planning and policy are key to designing age-friendly neighbourhoods with destinations that encourage older adults to get out and be physically active. We describe the mobility of older adults who live in a highly walkable neighbourhood. Specifically, we address the questions of 'where do older adults go?' (destinations) and 'how they get there?' (travel mode, physical activity). We recruited older adults (age 60+) who live in Vancouver's downtown core, an area acknowledged to be highly walkable (Walk Score(®): 94-97/100), and who leave their houses most days of the week. Participants (n = 184) recorded travel in diaries and wore an ActiGraph GT3X + accelerometer for 7 days during September to October 2012. We classified reported destinations according to the North American Industry Classification System, and analysed mobility [trip rates (overall and walking), steps, moderate to vigorous physical activity (MVPA)] and associations between travel and physical activity-related mobility measures. Key destinations were grocery stores (13.6% of trips), restaurants (7.2%), malls/marketplaces (5.5%), and others' homes (5.4%). Participants made 4.6 (std: 2.5) one-way trips/day, took 7910.1 (3871.1) steps/day, and accrued 39.2 (32.9) minutes/day of MVPA. Two-thirds of trips were by active modes (62.8% walk, 3.2% bike) and 22.4% were by car. Trip rates were significantly associated with physical activity outcomes. Older adults living in highly walkable neighbourhoods were very mobile and frequently used active transportation. Travel destinations signify the importance of nearby commercial and social opportunities, even in a highly walkable environment. The high rates of active travel and
Hedger, R D; Rikardsen, A H; Thorstad, E B
The effects of large, externally attached pop-up satellite archival tags (PSATs) were compared with those of small implanted data storage tags (DSTs) on adult Atlantic salmon Salmo salar during their ocean migration in regards to depth utilization, diving depth, diving rate, diving speed and temperatures experienced. Additionally the return rate and growth of individuals tagged with PSATs was compared with those of small acoustic tags and DSTs. Overall, the depth distribution of individuals tagged with PSATs was similar to that of those tagged with DSTs, reflecting the pelagic nature of S. salar at sea. Individuals tagged with PSATs, however, dived less frequently and to shallower depths, and dived and surfaced at slower velocities. Sea surface temperatures experienced by individuals tagged with PSATs were similar to those experienced by those tagged with DSTs for the same time of year, suggesting that there were no large differences in the ocean migration. Return rates did not depend on whether individuals were tagged with PSATs or not, indicating that survival at sea was not impacted by PSATs in comparison to small internal tags. Individuals tagged with PSATs, however, had a smaller increase in body mass than those tagged with acoustic tags or DSTs. It was concluded that PSATs are suitable for use in researching large-scale migratory behaviour of adult S. salar at sea, but that some effects on their behaviour from tagging must be expected. Effects of PSATs may be largest in the short term when S. salar are swimming in bursts at high speeds. Even though individuals tagged with PSATs performed deep and frequent dives, the results of this study suggest that untagged individuals would perform even deeper and more frequent dives than tagged individuals.
Hussen, Sophia A; Bowleg, Lisa; Sangaramoorthy, Thurka; Malebranche, David J
Black men in the USA experience disproportionately high rates of HIV infection, particularly in the Southeastern part of the country. We conducted 90 qualitative in-depth interviews with Black men living in the state of Georgia and analysed the transcripts using Sexual Script Theory to: (1) characterise the sources and content of sexual scripts that Black men were exposed to during their childhood and adolescence and (2) describe the potential influence of formative scripts on adult HIV sexual risk behaviour. Our analyses highlighted salient sources of cultural scenarios (parents, peers, pornography, sexual education and television), interpersonal scripts (early sex- play, older female partners, experiences of child abuse) and intrapsychic scripts that participants described. Stratification of participant responses based on sexual-risk behaviour revealed that lower- and higher-risk men described exposure to similar scripts during their formative years; however, lower-risk men reported an ability to cognitively process and challenge the validity of risk-promoting scripts that they encountered. Implications for future research are discussed.
Read, Stephen G.; Rendall, Maureen
Background: We examined the benefits of risperidone, including quality of life (QoL), in the treatment of violent and self-injurious behaviour in adults with moderate, severe or profound intellectual disability. Methods: Twenty-four participants received open-label, oral, flexible-dose risperidone of 0.5-6 mg/day for 12 weeks. Efficacy was…
Rüedi-Bettschen, Daniela; Zhang, Weining; Russig, Holger; Ferger, Boris; Weston, Anna; Pedersen, Else-Marie; Feldon, Joram; Pryce, Christopher R
Depression is diagnosed on the basis of abnormal positive affects (anhedonia) and negative affects (low mood, helplessness, coping deficit, fatigue), and associated physiological abnormalities include hyperactivity of the HPA endocrine system and autonomic nervous system. Adverse early life environments, including parent-offspring emotional and physical neglect, are associated with traits of altered physiological and neurobiological function and long-term predisposition to depression. Animal studies based on early life adversity can potentially yield environmental models of the developmental behavioural neurobiology of depression. In Wistar rats, we demonstrated that isolation of pups from dam and littermates at room temperature for 4 h per day on P1-14 (early deprivation, ED) led to adulthood anhedonia-like traits of reduced motivation to obtain gustatory reward and reduced social motivation, relative to subjects left undisturbed during infancy (non-handling, NH). We hypothesized that the depression-like effects of ED would be even more pronounced and multiple in the stress hyper-responsive Fischer rat strain. The effects of ED were studied relative to NH and 15 min of daily isolation (early handling, EH). Relative to NH and EH, which exhibited remarkably similar phenotypes, ED led, principally in males, to chronic traits of: reduced motivation for and consumption of gustatory reward; increased activity in the pre-test and test phases of the forced swim test; reduced coping behaviour in an aversive environment; attenuated plasma corticosterone stress response to a normal plasma ACTH stress response; increased hypertensive response to a novel environment; and increased prefrontal cortical serotonin. High sensitivity to an aversive early environment in male Fischer rats therefore constitutes an important model for the study of affective development and its neurobiology.
Hicks, Jasmin A; Hatzidis, Aikaterini; Arruda, Nicole L; Gelineau, Rachel R; De Pina, Isabella Monteiro; Adams, Kenneth W; Seggio, Joseph A
It is widely accepted that lifestyle plays a crucial role on the quality of life in individuals, particularly in western societies where poor diet is correlated to alterations in behavior and the increased possibility of developing type-2 diabetes. While exercising is known to produce improvements to overall health, there is conflicting evidence on how much of an effect exercise has staving off the development of type-2 diabetes or counteracting the effects of diet on anxiety. Thus, this study investigated the effects of voluntary wheel-running access on the progression of diabetes-like symptoms and open field and light-dark box behaviors in C57BL/6J mice fed a high-fat diet. C57BL/6J mice were placed into either running-wheel cages or cages without a running-wheel, given either regular chow or a high-fat diet, and their body mass, food consumption, glucose tolerance, insulin and c-peptide levels were measured. Mice were also exposed to the open field and light-dark box tests for anxiety-like behaviors. Access to a running-wheel partially attenuated the obesity and hyperinsulinemia associated with high-fat diet consumption in these mice, but did not affect glucose tolerance or c-peptide levels. Wheel-running strongly increased anxiety-like and decreased explorative-like behaviors in the open field and light-dark box, while high-fat diet consumption produced smaller increases in anxiety. These results suggest that voluntary wheel-running can assuage some, but not all, of the physiological problems associated with high-fat diet consumption, and can modify anxiety-like behaviors regardless of diet consumed.
Cushing, B S; Okorie, U; Young, L J
Centrally administered arginine vasopressin induces the formation of partner preferences in male prairie voles (Microtus ochrogaster). The expression of many vasopressin-regulated behaviours is testosterone dependent. In this study, we tested the hypothesis that early exposure to gonadal steroids are necessary to establish the typical response of adult male prairie voles to exogenous vasopressin, predicting that adult males which were castrated neonatally would not form partner preferences in response to centrally administered vasopressin. We also examined the effect of neonatal castration on the expression of vasopressin (V1a) receptors. Voles were castrated on the day of birth (NEOCAST), sham-castrated on the day of birth (NEOSHAM) or castrated as adults (ADULTCAST). With the exception of one group of neonatal sham males (NEOSHAM CON), which served as a control for the effects of vasopressin, as adults, all males received a 1- micro l intracerebroventricular injection of vasopressin (100 ng) in artificial cerebrospinal fluid. In addition, 2 weeks before testing, one group of neonatally castrated males received an implant of testosterone propionate (NEOCAST + TP). Between 60 and 90 days of age, an internal cannula was placed in the lateral cerebral ventricle and, 24 h later, males were injected with vasopressin. Subsequently, after an additional 15 min, males were cohabitated with a female 'partner' for 1 h. Immediately following cohabitation, males were placed in a Y-shaped partner preference test apparatus for 3 h, in which the male had access to the 'partner' and a novel female, 'stranger.' Time spent with the partner versus the stranger was compared within and between treatments. The results were found to support our hypothesis as the NEOSHAM and ADULTCAST males formed partner preferences, spending more time with the partner, and they spent significantly more time with their partner than did NEOSHAM CON, NEOCAST or NEOCAST + TP males. Replacement of
Di Rocco, Richard T.; Imre, Istvan; Johnson, Nicholas; Brown, Grant B
Sea lampreys Petromyzon marinus, an invasive pest in the Upper Great Lakes, avoid odours that represent danger in their habitat. These odours include conspecific alarm cues and predator cues, like 2-phenylethylamine hydrochloride (PEA HCl), which is found in the urine of mammalian predators. Whether conspecific alarm cues and predator cues function additively or synergistically when mixed together is unknown. The objectives of this experimental study were to determine if the avoidance response of sea lamprey to PEA HCl is proportional to the concentration delivered, and if the avoidance response to the combination of a predator cue (PEA HCl) and sea lamprey alarm cue is additive. To accomplish the first objective, groups of ten sea lampreys were placed in an artificial stream channel and presented with stepwise concentrations of PEA HCl ranging from 5 × 10−8 to 5 × 10−10 M and a deionized water control. Sea lampreys exhibited an increase in their avoidance behaviour in response to increasing concentrations of PEA HCl. To accomplish the second objective, sea lampreys were exposed to PEA HCl, conspecific alarm cue and a combination of the two. Sea lampreys responded to the combination of predator cue and conspecific alarm cue in an additive manner.
Otsuka, Tsuyoshi; Goda, Ryosei; Iwamoto, Ayaka; Kawai, Misato; Shibata, Satomi; Oka, Yoshiaki; Mizunoya, Wataru; Furuse, Mitsuhiro; Yasuo, Shinobu
In mammals, short photoperiod is associated with high depression- and anxiety-like behaviours with low levels of the brain serotonin and its precursor tryptophan (Trp). Because the brain Trp levels are regulated by its ratio to large neutral amino acids (Trp:LNAA) in circulation, this study elucidated whether diets of various protein sources that contain different Trp:LNAA affect depression- and anxiety-like behaviours in C57BL/6J mice under short-day conditions (SD). In the control mice on a casein diet, time spent in the central area in the open field test (OFT) was lower in the mice under SD than in those under long-day conditions (LD), indicating that SD exposure induces anxiety-like behaviour. The SD-induced anxiety-like behaviour was countered by an α-lactalbumin diet given under SD. In the mice that were on a gluten diet before transition to SD, the time spent in the central area in the OFT under SD was higher than that in the SD control mice. Alternatively, mice that ingested soya protein before the transition to SD had lower immobility in the forced swim test, a depression-like behaviour, compared with the SD control. Analysis of Trp:LNAA revealed lower Trp:LNAA in the SD control compared with the LD control, which was counteracted by an α-lactalbumin diet under SD. Furthermore, mice on gluten or soya protein diets before transition to SD exhibited high Trp:LNAA levels in plasma under SD. In conclusion, ingestion of specific proteins at different times relative to photoperiodic transition may modulate anxiety- and/or depression-like behaviours, partially through changes in plasma Trp:LNAA.
Roman, Erika; Meyerson, Bengt J; Hyytiä, Petri; Nylander, Ingrid
The aim of the present investigation was to compare the behavioural profiles in alcohol-preferring AA (Alko, alcohol) and alcohol-avoiding ANA (Alko, non-alcohol) rats. Twelve adult, alcohol-naïve male AA and ANA rats were tested in the recently established multivariate concentric square field (MCSF) test. The more traditional open field and elevated plus-maze tests were used as reference tests. Six weeks after the initial MCSF test, a repeated testing was used to explore differences in acquired recognition after a previous experience. The results revealed distinct differences between the two lines. The ANA rats were generally more active in the three tests. In the MCSF, parameters of risk taking and shelter seeking indicated differences between the two lines. The ANA rats had higher shelter seeking behaviour and less risk taking behaviour than the AA rats. Repeated exposure to the MCSF caused a general decrease in activity and reduction in the number of visits to the various zones, especially evident in the ANA rats. The ANA rats showed more shelter seeking than the AA rats and also more shelter seeking than in the first trial, supporting an "anxiety-like" profile in these rats. In conclusion, the parameters related to risk taking and shelter seeking revealed obvious differences between AA and ANA rats. The higher risk taking behaviour seen in the AA rats might relate to their innate propensity for high voluntary alcohol intake. The results are discussed in relation to the reported neurobiological differences and in relation to other alcohol-preferring and alcohol-avoiding rat lines.
Scholes-Balog, Kirsty E; Hemphill, Sheryl A; Evans-Whipp, Tracy J; Toumbourou, John W; Patton, George C
This study aimed to identify distinct developmental trajectories (sub-groups of individuals who showed similar longitudinal patterns) of cannabis use among Australian adolescents, and to examine associations between trajectory group membership and measures of social and behavioural adjustment in young adulthood. Participants (n=852, 53% female) were part of the International Youth Development Study. Latent class growth analysis was used to identify distinct trajectories of cannabis use frequency from average ages 12 to 19, across 6 waves of data. Logistic regression analyses and analyses of covariance were used to examine relationships between trajectory group membership and young adult (average age: 21) adjustment, controlling for a range of covariates. Three trajectories were identified: abstainers (62%), early onset users (11%), and late onset occasional users (27%). The early onset users showed a higher frequency of antisocial behaviour, violence, cannabis use, cannabis-related harms, cigarette use, and alcohol harms, compared to the abstinent group in young adulthood. The late onset occasional users reported a higher frequency of cannabis use, cannabis-related harms, illicit drug use, and alcohol harms, compared to the abstinent group in young adulthood. There were no differences between the trajectory groups on measures of employment, school completion, post-secondary education, income, depression/anxiety, or alcohol use problems. In conclusion, early onset of cannabis use, even at relatively low frequency during adolescence, is associated with poorer adjustment in young adulthood. Prevention and intervention efforts to delay or prevent uptake of cannabis use should be particularly focussed on early adolescence prior to age 12.
Doxorubicin and cyclophosphamide treatment produces anxiety-like behavior and spatial cognition impairment in rats: Possible involvement of hippocampal neurogenesis via brain-derived neurotrophic factor and cyclin D1 regulation.
Kitamura, Yoshihisa; Hattori, Sayo; Yoneda, Saori; Watanabe, Saori; Kanemoto, Erika; Sugimoto, Misaki; Kawai, Toshiki; Machida, Ayumi; Kanzaki, Hirotaka; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki
Many patients who have received chemotherapy to treat cancer experience depressive- and anxiety-like symptoms or cognitive impairment. However, despite the evidence for this, the underlying mechanisms are still not understood. This study investigated behavioral and biochemical changes upon treatment with doxorubicin and cyclophosphamide, focusing on mental and cognitive systems, as well as neurogenesis in male rats. Doxorubicin (2 mg/kg), cyclophosphamide (50 mg/kg), and the combination of doxorubicin and cyclophosphamide were injected intraperitoneally once per week for 4 weeks. In particular, the co-administration of doxorubicin and cyclophosphamide produced anhedonia-like, anxiety-like, and spatial cognitive impairments in rats. It also reduced both the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus and their survival. Serum brain-derived neurotrophic factor (BDNF) levels were decreased along with chemotherapy-induced decreases in platelet levels. However, hippocampal BDNF levels and Bdnf mRNA levels were not decreased by this treatment. On the other hand, hippocampal cyclin D1 levels were significantly decreased by chemotherapy. These results suggest that the co-administration of doxorubicin and cyclophosphamide induces psychological and cognitive impairment, in addition to negatively affecting hippocampal neurogenesis, which may be related to hippocampal cyclin D1 levels, but not hippocampal BDNF levels.
Proestrous compared to diestrous wildtype, but not estrogen receptor beta knockout, mice have better performance in the spontaneous alternation and object recognition tasks and reduced anxiety-like behavior in the elevated plus and mirror maze.
Walf, Alicia A; Koonce, Carolyn; Manley, Kevin; Frye, Cheryl A
17beta-Estradiol (E(2)) may influence cognitive and/or affective behavior in part via the beta isoform of the estrogen receptor (ERbeta). Endocrine status and behavior in cognitive (object recognition, T-maze), anxiety (open field, elevated plus maze, mirror maze, emergence), and motor/coordination (rotarod, activity chamber) tasks of proestrous and diestrous wildtype (WT) and ERbeta knockout (betaERKO) mice was examined. Proestrous (WT or betaERKO), versus diestrous, mice had higher E(2) and progestin levels in plasma, hippocampus, and cortex. The only effect of genotype on hormone levels was for corticosterone, such that betaERKO mice had higher concentrations of corticosterone than did WT mice. Proestrous WT, but not betaERKO, mice had improved performance in the object recognition (greater percentage of time with novel object) and T-maze tasks (greater percentage of spontaneous alternations) and less anxiety-like behavior in the plus maze (increased duration on open arms) and mirror chamber task (increased duration in mirror) than did diestrous mice. This pattern was not seen in the rotarod, open field, or activity monitor, suggesting effects may be specific to affective and cognitive behavior, rather than motor behavior/coordination. Thus, enhanced performance in cognitive tasks and anti-anxiety-like behavior of proestrous mice may require actions of ERbeta in the hippocampus and/or cortex.
Background The olfactory neuroepithelium lines the upper nasal cavity and is in direct contact with the external environment and the olfactory bulbs. The ability to self-renew throughout life and the reproducible recovery after injury, make it a model tissue to study mechanisms underlying neurogenesis. In this study, X-rays were used to disrupt proliferating olfactory stem cell populations and to assess their role in the cellular and morphological changes involved in olfactory neurogenic processes. Results We have analysed the histological and functional effects of a sub-lethal dose of X-rays on the adult mouse olfactory neuroepithelium at 2 hours, 24 hours, 1 week, 2 weeks and 5 weeks. We have shown an immediate cessation of proliferating olfactory stem cells as shown by BrdU, Ki67 and pH3 expression. At 24 hours there was an increase in the neural transcription factors Mash1 and Pax6 expression, and a disruption of the basal lamina and increase in glandular cell marker expression at 1 week post-irradiation. Coincident with these changes was an impairment of the olfactory function in vivo. Conclusions We have shown significant changes in basal cell proliferation as well as morphological changes in the olfactory neuroepithelium following X-ray irradiation. There is involvement of the basal lamina as well as a clear role for glandular and sustentacular cells. PMID:23113950
McElroy, Susan L; Mitchell, James E; Wilfley, Denise; Gasior, Maria; Ferreira-Cornwell, M Celeste; McKay, Michael; Wang, Jiannong; Whitaker, Timothy; Hudson, James I
In a published 11-week, placebo-controlled trial, 50 and 70 mg/d lisdexamfetamine dimesylate (LDX), but not 30 mg/d LDX, significantly reduced binge eating days (primary endpoint) in adults with binge eating disorder (BED). This report provides descriptions of LDX effects on secondary endpoints (Binge Eating Scale [BES]; Three-Factor Eating Questionnaire [TFEQ]; Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE]; and the Barratt Impulsiveness Scale, version 11 [BIS-11]) from that study. Week 11 least squares mean treatment differences favoured all LDX doses over placebo on the BES (p ≤ 0.03), TFEQ Disinhibition and Hunger subscales (all p < 0.05), and Y-BOCS-BE total, obsessive, and compulsive scales (all p ≤ 0.02) and on BIS-11 total score at 70 mg/d LDX (p = 0.015) and the TFEQ Cognitive Restraint subscale at 30 and 70 mg/d LDX (both p < 0.05). These findings indicate that LDX decreased global binge eating severity and obsessive-compulsive and impulsive features of BED in addition to binge eating days.
Background Brief interventions (BIs) have been shown to be effective in modifying hazardous drinking behaviours in a range of settings. However, they are underutilised in hospitals due to resource constraints. We explored the perspectives of admitted trauma patients about the appeal, acceptability and content of a Brief Intervention (BI) delivered via text messages. Methods Thirty mobile phone users (≥16 years old) admitted to Auckland City Hospital as a result of injury were recruited (December 2010 – January 2011). Participants were interviewed face-to-face during their hospital stay using a semi-structured interview guide that explored topics including perceptions of the proposed intervention to reduce hazardous drinking and related harm, and perceived acceptability of an m-health program. Where issues relating to content of messages were raised by participants these were also captured. In addition, a brief survey captured information on demographic information, mobile phone usage and type of phone, along with the frequency of alcohol use. Results 22 of the 30 participants were male, and almost half were aged 20 to 39 years. The majority of participants identified as New Zealand Europeans, six as Māori (New Zealand's indigenous population) and of the remainder two each identified as Pacific and of Asian ethnicity. Most (28/30) participants used a mobile phone daily. 18 participants were deemed to be drinking in a non-hazardous manner, seven were hazardous drinkers, and three were non-drinkers. Most participants (21/30) indicated that text messages could be effective in reducing hazardous drinking and related harms, with more than half (17/30) signalling they would sign-up. Factors identified that would increase receptiveness included: awareness that the intervention was evidence-based; participants readiness-to-change; informative messages that include the consequences of drinking and practical advice; non-judgemental messages; and ease-of-use. Areas of
Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M
The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α₂ adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence.
Cuijpers, Pim; Berking, Matthias; Andersson, Gerhard; Quigley, Leanne; Kleiboer, Annet; Dobson, Keith S
Objectif : Aucune méta-analyse récente n’a examiné les effets de la thérapie cognitivo-comportementale (TCC) sur la dépression adulte. Nous avons décidé de mener cette mise à jour de méta-analyses. Méthodes : Des études ont été identifiées lors de recherches systématiques dans les bases de données bibliographiques (PubMed, PsycINFO, Embase, et Cochrane library). Nous avons inclus des études qui examinent les effets de la TCC, comparé à des groupes témoins, d’autres psychothérapies, et la pharmacothérapie. Résultats : Un total de 115 études satisfaisaient aux critères d’inclusion. L’ampleur (AE) moyenne de l’effet de 94 comparaisons dans 75 études de TCC et de groupes témoins était au g de Hedges de 0,71 (IC à 95 % 0,62 à 0,79), ce qui correspond au nombre nécessaire pour traiter, soit 2,6. Toutefois, ceci peut être une surestimation de la véritable AE car nous avons trouvé de fortes indications de biais de publication (l’AE après correction pour biais était g = 0,53), et parce que l’AE des études de qualité supérieure était significativement plus faible (g = 0,53) que celle des études de qualité inférieure (g = 0,90). La différence entre les études de qualité supérieure et inférieure demeurait significative après correction pour d’autres caractéristiques des études dans une analyse de régression multivariée. Nous n’avons trouvé aucune indication que la TCC soit plus ou moins efficace que d’autres psychothérapies ou que la pharmacothérapie. Le traitement combiné était significativement plus efficace que la pharmacothérapie seule (g = 0,49). Conclusions : Il n’y a aucun doute que la TCC est un traitement efficace de la dépression adulte, bien que les effets aient pu en être surestimés jusqu’ici. La TCC est également la psychothérapie pour la dépression la plus étudiée, et elle a donc la plus grande évidence. Toutefois, d’autres traitements s’approchent de son efficacit
Rouel, Melissa; Raman, Jayanthi; Hay, Phillipa; Smith, Evelyn
Obesity and binge eating disorder (BED) are both associated with deficiencies in executive function. The Behaviour Rating Inventory of Executive Function - Adult Version (BRIEF-A) is a self-report measure that assesses executive function. This study aimed to examine the psychometric properties of the BRIEF-A in an obese population, with and without BED, and to explore the differences on the BRIEF-A in the obese, with and without BED, compared to normative sample. 98 obese participants (70 BED) completed the BRIEF-A, DASS-21 and several performance-based measures of executive function. 30 participants completed a repeat assessment two months later. There was evidence of good internal consistency and test-retest reliability, however evidence for construct and convergent validity was mixed. Additionally, it was found that obese individuals report significantly more executive function difficulties on the BRIEF-A than the normative sample. Further, obese with BED report more executive function difficulties than those without. This study shows some evidence of sound psychometric properties of the BRIEF-A in an obese sample, however more research is required to understand the nature of executive function being measured.
Unwin, Gemma; Tsimopoulou, Ioanna; Kroese, Biza Stenfert; Azmi, Sabiha
Relatively little is known about the application of cognitive behavioural therapy (CBT) to people with intellectual disabilities (ID). This review sought to synthesise available evidence on the effectiveness of CBT for anxiety or depression to assess the current level of evidence and make recommendations for future research. A comprehensive systematic literature search was conducted to identify qualitative and quantitative studies. Robust criteria were applied to select papers that were relevant to the review. Included papers were subject to quality appraisal. Eleven out of the 223 studies considered met our inclusion criteria and were included in the review in which CBT was used with participants with ID and anxiety (n=3), depression (n=4) or a mixed clinical presentation (n=4). There remains a paucity of evidence of effectiveness, however, the studies indicate that CBT is feasible and well-tolerated and may be effective in reducing symptoms of depression among adults with mild ID. Qualitative data reflect a positive perception of CBT amongst clients and carers. Further research is required to investigate the components of CBT, suitability for CBT, and requisite skills for CBT, which uses valid, sensitive and more holistic outcome measures.
Background Administration of exogenous corticosterone is an effective preclinical model of depression, but its use has involved primarily adult rodents. Using two different procedures of administration drawn from the literature, we explored the possibility of exogenous corticosterone models in adolescence, a time of heightened risk for mood disorders in humans. Methods In experiment 1, rats were injected with 40 mg/kg corticosterone or vehicle from postnatal days 30 to 45 and compared with no injection controls on behavior in the elevated plus maze (EPM) and the forced swim test (FST). Experiment 2 consisted of three treatments administered to rats from postnatal days 30 to 45 or as adults (days 70 to 85): either corticosterone (400 μg/ml) administered in the drinking water along with 2.5% ethanol, 2.5% ethanol or water only. In addition to testing on EPM, blood samples after the FST were obtained to measure plasma corticosterone. Analysis of variance (ANOVA) and alpha level of P < 0.05 were used to determine statistical significance. Results In experiment 1, corticosterone treatment of adolescent rats increased anxiety in the EPM and decreased immobility in the FST compared to no injection control rats. However, vehicle injected rats were similar to corticosterone injected rats, suggesting that adolescent rats may be highly vulnerable to stress of injection. In experiment 2, the intake of treated water, and thus doses delivered, differed for adolescents and adults, but there were no effects of treatment on behavior in the EPM or FST. Rats that had ingested corticosterone had reduced corticosterone release after the FST. Ethanol vehicle also affected corticosterone release compared to those ingesting water only, but differently for adolescents than for adults. Conclusions The results indicate that several challenges must be overcome before the exogenous corticosterone model can be used effectively in adolescents. PMID:22738136
Antenatal betamethasone produces protracted changes in anxiety-like behaviors and in the expression of microtubule-associated protein 2, brain-derived neurotrophic factor and the tyrosine kinase B receptor in the rat cerebellar cortex.
Pascual, Rodrigo; Valencia, Martina; Bustamante, Carlos
Using classic Golgi staining methods, we previously showed that the administration of synthetic glucocorticoid betamethasone in equivalent doses to those given in cases of human premature birth generates long-term alterations in Purkinje cell dendritic development in the cerebellar cortex. In the present study, we evaluated whether betamethasone alters the immunohistochemical expression of proteins that participate in cerebellar Purkinje cell dendritic development and maintenance, including microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor (BDNF) and the tyrosine kinase B receptor (TrkB), which are located predominantly in the cerebellar molecular layer where Purkinje cell dendritogenesis occurs. Consistent with our previous Golgi stain studies, we observed that animals prenatally exposed to a single course of betamethasone showed long-term alterations in the expression of MAP2, BDNF and TrkB. Additionally, these protracted molecular changes were accompanied by anxiety-like behaviors in the elevated plus maze and marble burying tests.
Gupta, Deepali; Radhakrishnan, Mahesh; Thangaraj, Devadoss; Kurhe, Yeshwant
Depression and anxiety are the most debilitating mood disorders with poor therapeutic recovery rates. In the last decades, 5-HT3 receptor antagonists have been identified as potential agents for mood disorders. The current investigation focuses on evaluating the, antidepressant and anti-anxiety like effects of a novel 5-HT3 antagonist, 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide). Preliminary, in vitro 5-HT3 receptor binding affinity was performed in isolated longitudinal muscle-myenteric plexus from the guinea pig ileum. Consequently, neurobehavioral effects of 4i in acute and chronic rodent models were evaluated. In addition, involvement of serotonergic system in the postulated effects of the compound was analyzed by in vivo assay. in vitro, 4i demonstrated high 5-HT3 receptor antagonistic activity (pA2, 7.6). in vivo acute study, 4i exhibited decreased duration of immobility in forced swim and tail suspension tests, and increased exploratory parameters as number and duration of nose-poking in hole board test and latency and time spent in aversive brightly illuminated light chamber in light-dark model. Moreover, in chronic model of depression, i.e., olfactory bulbectomy with behavioral deficits, 4i reversed depressive anhedonia in sucrose preference test and anxious hyperactive behavior in open field test in rats. Furthermore, synergistic effect of 4i with fluoxetine (a selective serotonin reuptake inhibitor) and inhibitory effect of 1-(m-chlorophenyl)-biguanide (a 5-HT3 receptor agonist) revealed serotonergic modulation by 4i mediated 5-HT3 receptor antagonism, which was further confirmed by potentiation of 5-hydroxytryptophan (a serotonin synthesis precursor) induced head twitch response. These findings suggest the potential antidepressant and anti-anxiety like effects of 4i, which may be related to the modulation of serotonergic system.
Marsh, Samantha; Ni Mhurchu, Cliona; Maddison, Ralph
Sedentary screen time may be an important determinant of childhood obesity. A number of potential mechanisms to explain the link between screen time and increased bodyweight have been proposed; however, the relationship appears to be best explained by the effects on dietary intake, which is attributed to either food advertising or effects independent of food advertising. Technological advances have allowed for greater accessibility and exposure to advertisement-free screen-based media. This review was conducted to systematically synthesise the evidence from laboratory based studies which have investigated the non-advertising effects of screen time (TV viewing, sedentary video games, and computer use) on dietary intake in children, adolescents, and young adults. MEDLINE, PubMed, PsychInfo, CINAHL, and Embase were searched from inception through 5 July 2013. Ten trials met the inclusion criteria and were included in the review. Risk of study bias was judged to range from low to high. Screen time in the absence of food advertising was consistently found to be associated with increased dietary intake compared with non-screen behaviours. Suggested explanations for this relationship included: distraction, interruption of physiologic food regulation, screen time as a conditioned cue to eat, disruption of memory formation, and the effects of the stress-induced reward system. Due to the limited number of high-quality studies available for this review, our findings are preliminary. More work is required to better establish the link between dietary intake and advertisement-free screen time and assess whether differences exist between the different screen-based activities.
Tyler, Elizabeth; Lobban, Fiona; Sutton, Chris; Depp, Colin; Johnson, Sheri; Laidlaw, Ken; Jones, Steven H
Introduction Bipolar disorder is a severe and chronic mental health problem that persists into older adulthood. The number of people living with this condition is set to rise as the UK experiences a rapid ageing of its population. To date, there has been very little research or service development with respect to psychological therapies for this group of people. Methods and analysis A parallel two-arm randomised controlled trial comparing a 14-session, 6-month Recovery-focused Cognitive-Behavioural Therapy for Older Adults with bipolar disorder (RfCBT-OA) plus treatment as usual (TAU) versus TAU alone. Participants will be recruited in the North-West of England via primary and secondary mental health services and through self-referral. The primary objective of the study is to evaluate the feasibility and acceptability of RfCBT-OA; therefore, a formal power calculation is not appropriate. It has been estimated that randomising 25 participants per group will be sufficient to be able to reliably determine the primary feasibility outcomes (eg, recruitment and retention rates), in line with recommendations for sample sizes for feasibility/pilot trials. Participants in both arms will complete assessments at baseline and then every 3 months, over the 12-month follow-up period. We will gain an estimate of the likely effect size of RfCBT-OA on a range of clinical outcomes and estimate parameters needed to determine the appropriate sample size for a definitive, larger trial to evaluate the effectiveness and cost-effectiveness of RfCBT-OA. Data analysis is discussed further in the Analysis section in the main paper. Ethics and dissemination This protocol was approved by the UK National Health Service (NHS) Ethics Committee process (REC ref: 15/NW/0330). The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and local, participating NHS trusts. Trial registration number ISRCTN13875321; Pre
Gooding, Margaret A; Atkinson, Jim L; Duncan, Ian J H; Niel, Lee; Shoveller, Anna K
The effects of dietary carbohydrate and fat on feline health are not well understood. The effects of feeding diets moderately high in fat (HF; n 10; 30 % fat, 26 % carbohydrate as fed) or carbohydrate (HC; n 10; 11 % fat, 47 % carbohydrate), for 84 d, were investigated in healthy, adult cats (3·5 (sd 0·5) years). Data on indirect calorimetry, blood biomarkers, activity, play and cognition were collected at baseline, and at intervals throughout the study. Body composition was measured by dual-energy X-ray absorptiometry at baseline and on day 85. There were no significant main effects of diet on body weight and composition. When data were analysed over study day within diet, cats fed HF diets experienced a significant increase in body fat (P = 0·001) and body weight (P = 0·043) in contrast to cats consuming the HC diet that experienced no change in body fat or body weight (P = 0·762) throughout the study. Overall, energy expenditure was similar between diets (P = 0·356 (fasted), P = 0·086 (postprandial)) and respiratory quotient declined with exposure to the HF diet and increased with exposure to the HC diet (P < 0·001; fasted and postprandial). There was no difference in insulin sensitivity as an overall effect of diet (P = 0·266). Activity declined from baseline with exposure to both diets (HC: P = 0·002; HF: P = 0·01) but was not different between diets (P = 0·247). There was no effect of diet on play (P = 0·387) and cats consuming either the HF or HC diet did not successfully learn the cognitive test. Overall, cats adapt to dietary macronutrient content, and the implications of feeding HC and HF diets on risk for adiposity as driven by metabolic and behavioural mechanisms are discussed.
Ljótsson, Brjánn; Hedman, Erik; Svanborg, Cecilia; Kaldo, Viktor; Lindefors, Nils
Background Although the effectiveness of therapist-guided internet-based cognitive behaviour therapy (ICBT) for treating depression has been well documented, knowledge of outcome predictors and risk factors associated with lower treatment response is limited, especially when the treatment has been conducted within a naturalistic clinical setting. Identification of such factors is important for clinicians when making treatment recommendations. Methods Data from a large cohort (N = 1738) of adult outpatients having been treated with ICBT for depression at an outpatient psychiatric clinic were analysed. A multilevel modelling approach was used to identify patient and treatment variables associated with the speed of recovery during treatment using weekly measurements of the Montgomery Åsberg Depression Rating Scale Self-Rated (MADRS-S). Outcomes Adhering to the treatment, perceiving it as credible and working full-time emerged as predictors of a faster pace of recovery and were also associated with a lower level of depression at the end of treatment. Higher pre-treatment depression and sleep problems were associated with a greater improvement rate, but predicted higher depression after treatment. Having a history of psychotropic medication was associated with both slower improvement and higher post-treatment depression. Conclusion Perceived credibility of ICBT is a strong predictor of treatment response. Assessing patient beliefs and expectations may be a useful aid for clinicians when identifying those who are more or less likely to benefit from ICBT. Helping patients improve expectations prior to treatment may be an important goal for clinicians during the initial assessment phase. PMID:27618548
Flodgren, Gerd; Deane, Katherine; Dickinson, Heather O; Kirk, Sara; Alberti, Hugh; Beyer, Fiona R; Brown, James G; Penney, Tarra L; Summerbell, Carolyn D; Eccles, Martin P
Background The prevalence of obesity is increasing globally and will, if left unchecked, have major implications for both population health and costs to health services. Objectives To assess the effectiveness of strategies to change the behaviour of health professionals and the organisation of care to promote weight reduction in overweight and obese people. Search methods We updated the search for primary studies in the following databases, which were all interrogated from the previous (version 2) search date to May 2009: The Cochrane Central Register of Controlled Trials (which at this time incorporated all EPOC Specialised Register material) (The Cochrane Library 2009, Issue 1), MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), and PsycINFO (Ovid). We identified further potentially relevant studies from the reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) that compared routine provision of care with interventions aimed either at changing the behaviour of healthcare professionals or the organisation of care to promote weight reduction in overweight or obese adults. Data collection and analysis Two reviewers independently extracted data and assessed study quality. Main results We included six RCTs, involving more than 246 health professionals and 1324 overweight or obese patients. Four of the trials targeted professionals and two targeted the organisation of care. Most of the studies had methodological or reporting weaknesses indicating a risk of bias. Meta-analysis of three trials that evaluated educational interventions aimed at GPs suggested that, compared to standard care, such interventions could reduce the average weight of patients after a year (by 1.2 kg, 95% CI −0.4 to 2.8 kg); however, there was moderate unexplained heterogeneity between their results (I2 = 41%). One trial found that reminders could change doctors’ practice, resulting in a significant reduction in weight among men (by 11.2 kg, 95% CI 1.7 to 20
Thompson, Ralph R.J.; Paul, Elizabeth S.; Radford, Andrew N.; Purser, Julia; Mendl, Michael
Fish are increasingly popular subjects in behavioural and neurobiological research. It is therefore important that they are housed and handled appropriately to ensure good welfare and reliable scientific findings, and that species-appropriate behavioural tests (e.g. of cognitive/affective states) are developed. Routine handling of captive animals may cause physiological stress responses that lead to anxiety-like states (e.g. increased perception of danger). In fish, these may be particularly pronounced when handling during tank-to-tank transfer involves removal from water into air. Here we develop and use a new combined scototaxis (preference for dark over light areas) and novel-tank-diving test, alongside conventional open-field and novel-object tests, to measure the effects of transferring three-spined sticklebacks (Gasterosteus aculeatus) between tanks using a box or net (in and out of water respectively). Preference tests for dark over light areas confirmed the presence of scototaxis in this species. Open-field and novel-object tests failed to detect any significant differences between net and box-handled fish. However, the combined diving and scototaxis detected consistent differences between the treatments. Net-handled fish spent less time on the dark side of the tank, less time in the bottom third, and kept a greater distance from the ‘safe’ bottom dark area than box-handled fish. Possible explanations for this reduction in anxiety-like behaviour in net-handled fish are discussed. The combined diving and scototaxis test may be a sensitive and taxon-appropriate method for measuring anxiety-like states in fish. PMID:26965568
Thompson, Ralph R J; Paul, Elizabeth S; Radford, Andrew N; Purser, Julia; Mendl, Michael
Fish are increasingly popular subjects in behavioural and neurobiological research. It is therefore important that they are housed and handled appropriately to ensure good welfare and reliable scientific findings, and that species-appropriate behavioural tests (e.g. of cognitive/affective states) are developed. Routine handling of captive animals may cause physiological stress responses that lead to anxiety-like states (e.g. increased perception of danger). In fish, these may be particularly pronounced when handling during tank-to-tank transfer involves removal from water into air. Here we develop and use a new combined scototaxis (preference for dark over light areas) and novel-tank-diving test, alongside conventional open-field and novel-object tests, to measure the effects of transferring three-spined sticklebacks (Gasterosteus aculeatus) between tanks using a box or net (in and out of water respectively). Preference tests for dark over light areas confirmed the presence of scototaxis in this species. Open-field and novel-object tests failed to detect any significant differences between net and box-handled fish. However, the combined diving and scototaxis detected consistent differences between the treatments. Net-handled fish spent less time on the dark side of the tank, less time in the bottom third, and kept a greater distance from the 'safe' bottom dark area than box-handled fish. Possible explanations for this reduction in anxiety-like behaviour in net-handled fish are discussed. The combined diving and scototaxis test may be a sensitive and taxon-appropriate method for measuring anxiety-like states in fish.
The recovery of acetylcholinesterase activity and the progression of neuropathological and pathophysiological alterations in the rat basolateral amygdala after soman-induced status epilepticus: relation to anxiety-like behavior
Prager, Eric M.; Aroniadou-Anderjaska, Vassiliki; Almeida-Suhett, Camila P.; Figueiredo, Taiza H.; Apland, James P.; Rossetti, Franco; Olsen, Cara H.; Braga, Maria F.M.
Organophosphorus nerve agents are powerful neurotoxins that irreversibly inhibit acetylcholinesterase (AChE) activity. One of the consequences of AChE inhibition is the generation of seizures and status epilepticus (SE), which cause brain damage, resulting in long-term neurological and behavioral deficits. Increased anxiety is the most common behavioral abnormality after nerve agent exposure. This is not surprising considering that the amygdala, and the basolateral nucleus of the amygdala (BLA) in particular, plays a central role in anxiety, and this structure suffers severe damage by nerve agent-induced seizures. In the present study, we exposed male rats to lethal doses of the nerve agent soman, and determined the time course of recovery of AChE activity, along with the progression of neuropathological and pathophysiological alterations in the BLA, during a 30-day period after exposure. Measurements were taken at 24 hours, 7 days, 14 days, and 30 days after exposure, and at 14 and 30 days, anxiety-like behavior was also evaluated. We found that more than 90% of AChE is inhibited at the onset of SE, and AChE inhibition remains at this level 24 hours later, in the BLA, as well as in the hippocampus, piriform cortex, and prelimbic cortex, which we analyzed for comparison. AChE activity recovered by day 7 in the BLA and day 14 in the other three regions. Significant neuronal loss and neurodegeneration were present in the BLA at 24 hours and throughout the 30-day period. There was no significant loss of GABAergic interneurons in the BLA at 24 hours post-exposure. However, by day 7, the number of GABAergic interneurons in the BLA was reduced, and at 14 and 30 days after soman, the ratio of GABAergic interneurons to the total number of neurons was lower compared to controls. Anxiety-like behavior in the open-field and the acoustic startle response tests was increased at 14 and 30 days post-exposure. Accompanying pathophysiological alterations in the BLA – studied in
Mi, Guiyun; Gao, Yunyun; Yan, Hui; Jin, Xiao; Ye, Enmao; Liu, Shuai; Gong, Zehui; Yang, Hongju; Yang, Zheng
Methamphetamine (METH), a substance with a high potential for abuse and addiction, is a serious worldwide public health problem. METH addicts often show extreme paranoia, anxiety, and depression. Thus, there is no effective medication for the treatment of METH-induced abnormalities. In the present study, we investigated the effects of l-Scoulerine (l-SLR), a tetrahydroprotoberberine (THPBS) alkaloid, on METH-induced anxiety-like behaviour in zebrafish and METH-induced addictive behavior in mice. In the novel tank test, acute administration of METH (2 mg/L) induced a significant decrease in the number of total vertical transitions and time spent in the upper zone. Moreover, METH produced significant avoidance behaviour showing increased swimming time in the central area and high speed movement in the mirror area in the mirror stimulation test; these anxiety-like changes were attenuated by l-SLR. Chronic administration of METH (2 mg/kg) produced a steady increase in locomotor activity and conditioned place preference in mice. l-SLR (5 mg/kg) failed to reduce acute METH-induced hyperlocomotion, but attenuated chronic METH-induced behavioural sensitization and significantly blocked the expression of conditioned place preference induced by METH in mice. The present study suggests that l-SLR may be a promising agent for the treatment of addiction and anxiety induced by METH.
Tailored, iterative, printed dietary feedback is as effective as group education in improving dietary behaviours: results from a randomised control trial in middle-aged adults with cardiovascular risk factors
Background Tailored nutrition interventions have been shown to be more effective than non-tailored materials in changing dietary behaviours, particularly fat intake and fruit and vegetable intake. But further research examining efficacy of tailored nutrition education in comparison to other nutrition education methods and across a wider range of dietary behaviours is needed. The Stages to Healthy Eating Patterns Study (STEPs) was an intervention study, in middle-aged adults with cardiovascular risk factors, to examine the effectiveness of printed, tailored, iterative dietary feedback delivered by mail in improving short-term dietary behaviour in the areas of saturated fat, fruit, vegetable and grain and cereal intake. Methods STEPs was a 3-month randomised controlled trial with a pre and post-test design. There were three experimental conditions: 1) tailored, iterative, printed dietary feedback (TF) with three instalments mail-delivered over a 3-month period that were re-tailored to most recent assessment of dietary intake, intention to change and assessment of self-adequacy of dietary intake. Tailoring for dietary intake was performed on data from a validated 63-item combination FFQ designed for the purpose 2) small group nutrition education sessions (GE): consisting of two 90-minute dietitian-led small group nutrition education sessions and 3) and a wait-listed control (C) group who completed the dietary measures and socio-demographic questionnaires at baseline and 3-months later. Dietary outcome measures in the areas of saturated fat intake (g), and the intake of fruit (serves), vegetables (serves), grain and cereals as total and wholegrain (serves) were collected using 7-day estimated dietary records. Descriptive statistics, paired t-tests and general linear models adjusted for baseline dietary intake, age and gender were used to examine the effectiveness of different nutrition interventions. Results The TF group reported a significantly greater increase in
Eklund, Malin B; Johansson, Linda M; Uvnäs-Moberg, Kerstin; Arborelius, Lotta
Repeated, prolonged maternal separation has been suggested to model the development of a depression-like syndrome in rats. The long separations from the pups have been proposed to be stressful for the dams, which in turn could mediate the changes seen in adult offspring. In the present study we investigated whether prolonged maternal separation really is stressful for rat dams by studying parameters known to be affected by long-term stress such as spontaneous motor activity, anxiety-like behaviour, adrenal gland weight and plasma corticosterone levels. Dams were separated from their litter for either 4 h (MS240) or 15 min (MS15) on eight random days during postnatal day 1-14, or left undisturbed (animal facility reared, AFR). After weaning MS240 dams showed decreased peripheral activity and habituated slower in horizontal activity. On the contrary, MS15 dams showed more peripheral activity and less rearing activity compared to both AFR and MS240 dams when habituated to the testing apparatus, suggesting that MS15 dams are more anxious. The adrenal glands from MS15 dams weighed significantly less and plasma corticosterone levels were significantly higher compared to AFR and MS240 dams. These results suggest that repeated brief maternal separations from pups could be stressful for rat mothers, whereas prolonged separations are not. Since these results are in contrast to the current notion that the short separation procedure may be considered as a safe milieu, whereas the prolonged separations have been suggested to be stressful for both dams and pups, further studies in this field are warranted.
Unwin, Gemma; Deb, Shoumitro; Deb, Tanya
Background: In the UK, people with intellectual disabilities who exhibit aggressive behaviour often receive community-based specialist health services from a community learning disability team (CLDT). Our aim was to estimate costs associated with this provision and to identify predictors of higher costs. Method: Costs were estimated for 60 adults…
Hjalmarsson, Erik; Kaver, Anna; Perseius, Kent-Inge; Cederberg, Kerstin; Ghaderi, Ata
The aim of this paper was to investigate the feasibility and impact of dialectical behaviour therapy (DBT) for patients with borderline personality disorder (BPD) in a clinical outpatient setting. Eighteen clinicians were trained and supervised in using DBT. Twenty-seven female patients were assessed on a number of variables before the treatment,…
Finnanger, Torun Gangaune; Olsen, Alexander; Skandsen, Toril; Lydersen, Stian; Vik, Anne; Evensen, Kari Anne I.; Catroppa, Cathy; Håberg, Asta K.; Andersson, Stein; Indredavik, Marit S.
Survivors of moderate-severe Traumatic Brain Injury (TBI) are at risk for long-term cognitive, emotional, and behavioural problems. This prospective cohort study investigated self-reported executive, emotional, and behavioural problems in the late chronic phase of moderate and severe TBI, if demographic characteristics (i.e., age, years of education), injury characteristics (Glasgow Coma Scale score, MRI findings such as traumatic axonal injury (TAI), or duration of posttraumatic amnesia), symptoms of depression, or neuropsychological variables in the first year after injury predicted long-term self-reported function. Self-reported executive, emotional, and behavioural functioning were assessed among individuals with moderate and severe TBI (N = 67, age range 15–65 years at time of injury) 2–5 years after TBI, compared to a healthy matched control group (N = 72). Results revealed significantly more attentional, emotional regulation, and psychological difficulties in the TBI group than controls. Demographic and early clinical variables were associated with poorer cognitive and emotional outcome. Fewer years of education and depressive symptoms predicted greater executive dysfunction. Younger age at injury predicted more aggressive and rule-breaking behaviour. TAI and depressive symptoms predicted Internalizing problems and greater executive dysfunction. In conclusion, age, education, TAI, and depression appear to elevate risk for poor long-term outcome, emphasising the need for long-term follow-up of patients presenting with risk factors. PMID:26549936
Martin, Emma; McKenzie, Karen; Newman, Emily; Bowden, Keith; Morris, Paul Graham
Researchers suggest that people with an intellectual disability (ID) undertake less physical activity than the general population and many rely, to some extent, on others to help them to access activities. The Theory of Planned Behaviour (TPB) model was previously found to significantly predict the intention of care staff to facilitate a healthy…
Painsipp, E; Sperk, G; Herzog, H; Holzer, P
Neuropeptide-Y acting through Y1 receptors reduces anxiety and stress sensitivity in rodents. In Y1 receptor knockout (Y1⁻/⁻) mice, however, anxiety-related behaviour is altered only in a context-dependent manner. Here, we investigated whether stress causes a delayed change in the emotional-affective behaviour of female Y1⁻/⁻ mice. Locomotor and anxiety-related behaviour was assessed with the elevated plus-maze (EPM) test and depression-like behaviour with the forced swim test (FST). These behavioural tests were also used as experimental stress paradigms. Locomotion and anxiety-like behaviour did not differ between naïve control and Y1⁻/⁻ mice. One week after the FST, locomotion was reduced in control animals but unchanged in Y1⁻/⁻ mice, whereas anxiety-like behaviour remained unaltered in both genotypes. Depression-like behaviour (immobility) was identical in naïve control and Y1⁻/⁻ mice but, 1 week after the EPM test, was attenuated in Y1⁻/⁻ mice relative to control animals. Our data show that naïve female Y1⁻/⁻ mice do not grossly differ from female control animals in their locomotor and depression-like behaviour. Exposure to the stress associated with behavioural testing, however, leads to delayed genotype-dependent differences in locomotion and depression-like behaviour. These findings attest to a role of Y1 receptor signalling in the control of stress coping and/or adaptation.
Exposure to a Highly Caloric Palatable Diet During Pregestational and Gestational Periods Affects Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Adiposity and Anxiety-Like Behaviors in Male Rat Offspring
Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemí; Alén, Francisco; Antón, María; Decara, Juan; Ouro, Daniel; Orio, Laura; Suarez, Juan; Lutz, Beat; Rodríguez de Fonseca, Fernando; Gómez de Heras, Raquel
Exposure to unbalanced diets during pre-gestational and gestational periods may result in long-term alterations in metabolism and behavior. The contribution of the endocannabinoid system to these long-term adaptive responses is unknown. In the present study, we investigated the impact of female rat exposure to a hypercaloric-hypoproteic palatable diet during pre-gestational, gestational and lactational periods on the development of male offspring. In addition, the hypothalamic and hippocampal endocannabinoid contents at birth and the behavioral performance in adulthood were investigat