Defensive Burying Research Articles

Behavioural assays to model cognitive and affective dimensions of depression and anxiety in rats.

Animal models have been used extensively to investigate neuropsychiatric disorders, such as depression, and their treatment. However, the aetiology and pathophysiology of many such disorders are largely unknown, which makes validation of animal models particularly challenging. Furthermore, many diagnostic symptoms are difficult to define, operationalize and quantify, especially in experimental animals such as rats. Thus, rather than attempting to model complex human syndromes such as depression in their entirety, it can be more productive to define and model components of the illness that may account for clusters of co-varying symptoms, and that may share common underlying neurobiological mechanisms. In preclinical investigations of the neural regulatory mechanisms linking stress to depression and anxiety disorders, as well as the mechanisms by which chronic treatment with antidepressant drugs may exert their beneficial effects in these conditions, we have employed a number of behavioural tests in rats to model specific cognitive and anxiety-like components of depression and anxiety disorders. In the present study, we review the procedures for conducting four such behavioural assays: the attentional set-shifting test, the elevated-plus maze, the social interaction test and the shock-probe defensive burying test. The purpose is to serve as a guide to the utility and limitations of these tools, and as an aid in optimising their use and productivity.

Anxiolytic-like effect of neuropeptide S in the rat defensive burying

Neuropeptide S (NPS) has been recently identified as the endogenous ligand of a previously orphan G-protein-coupled receptor now named NPSR. Both NPS and its receptor are expressed in the brain, where they modulate different functions. In particular, it has been demonstrated that intracerebroventricular (i.c.v.) injection of NPS in rodents increases wakefulness and promotes anxiolytic-like effects. In the present study we used the defensive burying (DB) test in rats to further investigate the action of human NPS (0.1–10 nmol, i.c.v.) on anxiety-related behaviors. Diazepam (1.5 mg/kg, i.p.) and caffeine (20 mg/kg, i.p.) were used in parallel experiments as standard anxiolytic and anxiogenic drugs, respectively. None of the tested drugs produced statistical differences in the latency to contact the probe, burying behavior latency, number of shocks received or immobility/freezing duration. Caffeine increased cumulative burying behavior and the buried bedding height in a statistically significant manner thus promoting anxiogenic like effects. Opposite results were obtained with diazepam that significantly reduced these behavioral parameters. The anxiolytic-like action of diazepam was mimicked by NPS that reduced cumulative burying behavior in a dose dependent manner. Collectively, robust anxiolytic-like effects were recorded in response to NPS in the DB test. These results are of particular interest since the outcome of this assay is marginally influenced by drug effects on locomotor activity. In conclusion, we provide further evidence that NPS evokes genuine anxiolytic-like effects in the rat; therefore NPSR selective agonists are worthy of development as innovative drugs for the treatment of anxiety disorders.

The lateral hypothalamus and anterior hypothalamic nucleus differentially contribute to rats' defensive responses in the elevated plus-maze and shock-probe burying tests

Lesions or pharmacological inhibition of the lateral septum reduce rats' open-arm avoidance in the elevated plus-maze and their burying behavior in the shock-probe test. The current study examined whether hypothalamic areas that receive direct input from the lateral septum also influence open-arm avoidance and defensive burying. Bilateral infusions of the GABA-A receptor agonist muscimol (20 ng) into the lateral hypothalamus selectively increased rats' open-arm avoidance without affecting shock-probe burying. In contrast, infusions of muscimol into the anterior hypothalamic nucleus suppressed burying without affecting rats' open-arm avoidance. These dissociations suggest that the lateral hypothalamus contributes to the exploration of potentially threatening environments, whereas the anterior hypothalamus influences defensive responses to proximal discrete threat stimuli.

MPZP: A novel small molecule corticotropin-releasing factor type 1 receptor (CRF 1) antagonist

The extrahypothalamic stress peptide corticotropin-releasing factor (CRF) system is an important regulator of behavioral responses to stress. Dysregulation of CRF and the CRF type 1 receptor (CRF 1) system is hypothesized to underlie many stress-related disorders. Modulation of the CRF 1 system by non-peptide antagonists currently is being explored as a therapeutic approach for anxiety disorders and alcohol dependence. Here, we describe a new, less hydrophilic ( cLogP ∼ 2.95), small molecule, non-peptide CRF 1 antagonist with high affinity ( K i = 4.9 nM) and specificity for CRF 1 receptors: N, N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5- a] pyrimidin-7-amine (MPZP). The compound was systemically administered to adult male rats in two behavioral models dependent on the CRF 1 system: defensive burying (0, 5, 20 mg/kg, n = 6–11 for each dose) and alcohol dependence (0, 5, 10, 20 mg/kg, n = 8 for each self-administration group). Acute administration of MPZP reduced burying behavior in the defensive burying model of active anxiety-like behavior. MPZP also attenuated withdrawal-induced excessive drinking in the self-administration model of alcohol dependence without affecting nondependent alcohol drinking or water consumption. The present findings support the proposed significance of the CRF 1 system in anxiety and alcohol dependence and introduce a promising new compound for further development in the treatment of alcohol dependence and stress-related disorders.

Rats with Extended Access to Cocaine Exhibit Increased Stress Reactivity and Sensitivity to the Anxiolytic-Like Effects of the mGluR 2/3 Agonist LY379268 during Abstinence

Metabotropic glutamate 2/3 receptors (mGluR2/3) are emerging targets for the reduction of stress that contributes to drug relapse. The effect of a history of cocaine escalation on stress reactivity during abstinence and the role of mGlu2/3 receptors in stress in these animals were tested. Experiment 1-Rats trained to self-administer cocaine, under short (ShA, 1-h) or long (LgA, 6-h) access conditions, or noncaloric food pellets (Ctrl, 1-h), were tested for stress reactivity in the shock-probe defensive burying test following 1, 14, 42, or 84 days of abstinence. Experiment 2-Experimentally naive rats receiving the mGlu2/3 receptor agonist LY379268 (0, 0.3, 1.0, or 3.0 mg/kg) were tested in the defensive burying test to establish the anxiolytic efficacy of this compound in this model. Experiment 3-Rats with a history of ShA vs LgA cocaine self-administration, or a history of operant responding reinforced by noncaloric food pellets, were tested in the defensive burying test, following administration of LY379268 (0.3, 1.0, or 3.0 mg/kg) at 14 days of abstinence. LgA rats exhibited a two- to threefold increase in defensive burying at 1, 14, and 42 days of abstinence compared to ShA or control animals. LY379268 (3.0 mg/kg) reduced burying in all groups, whereas the 1.0-mg/kg dose reduced burying only in the LgA group. A robust and enduring increase in stress reactivity developed in rats with a history of daily 6-h access to cocaine. The anxiolytic-like effects of LY379268 identify mGlu2/3 receptors as targets for ameliorating stress-associated relapse risk, and point toward the possibility that a history of cocaine escalation in rats may modify glutamatergic function.

Effects of LPS on the behavioural stress response of genetically selected aggressive and nonaggressive wild house mice

The bacterial endotoxin lipopolysaccharide (LPS) exerts strong effects on the immune-neuroendocrine network. On behaviour, LPS induces the symptoms of sickness behaviour. Otherwise, LPS challenge shares with psychological stress some common physiological adaptations. The proposal of this study was to analyse the effects of the LPS injection on the behavioural response in the shock-probe defensive burying test of two wild house mouse lines genetically selected for short (SAL) and long (LAL) latency to attack a conspecific. It is known that with previous exposure to stress, each of these lines exhibits behaviour in the burying test that is closely related to their different neuroendocrine patterns of response, with higher expression of burying in the SAL and immobility in the LAL mice. LPS (0.5 ml, 375 μg/Kg) or sterile saline (0.9%) was i.p. injected 3.5 h before the beginning of the test. Non-injected mice were used as a general control of stress of handling and drug effect. The following behaviours were analyzed: defensive burying, immobility, rearing, grooming, exploration and jumping. The procedure of injection was found to be a stimulus that induced behavioural alterations in the SAL and LAL mice. Some behavioural changes induced by saline injection resembled that induced by LPS injection; in both lines an increase in immobility as well as a decrease in burying behaviour was observed. It is noteworthy that the LAL mice increased more their immobility than the SAL mice after saline or LPS injection, and the decrease in burying in the saline and LPS-injected mice was lower in the SAL than in the LAL mice. These results and others discussed in the text suggest that the active coping strategy of SAL mice and the passive coping strategy of the LAL mice, the hallmark of each line in the shock-probe burying test is present after psychological as well as LPS challenge exposure.

Individual differences predict susceptibility to conditioned fear arising from psychosocial trauma

Background Classical Pavlovian fear conditioning has been widely used in preclinical studies to gain insights into anxiety-related disorders. In this study we examined whether pre-existing behavioral differences, and/or behavioral differences displayed during fear induction, predict the severity of the conditioned fear response that can develop after an episode of psychosocial conflict. Methods Prior to conditioning, male rats (intruders) were behaviorally assessed using the novel environment exploration and defensive burying tests. These animals were subsequently placed in the territory of an older male (resident) that invariably attacked the intruder. Results Upon return to this territory 24 h later, intruders moved less than controls and produced more distress vocalizations, indicating conditioned fear to context. Additionally, analyses revealed that both pre-existing behavioral differences, and the animal’s response during social conflict, predicted the magnitude of the subsequent conditioned fear response. Specifically, animals that engaged in higher levels of novel environment exploration, that exhibited a greater number of defensive burying behaviors, and that demonstrated higher levels of fighting and guarding during social conflict, displayed less evidence of conditioned fear. Conclusion These findings show that the behavioral variability existent within a normal outbred population can predict the magnitude of the conditioned fear response.

Acute paternal alcohol use affects offspring development and adult behavior

Swiss Webster pups were fathered by sires given either an acute dose of alcohol (alcohol-sired) or saline (saline-sired) 12–24 h before mating. The same sires were used to father both groups of pups. Alcohol-sired pups were significantly lighter at birth and for the following three weeks than were saline-sired pups. Significantly more pups were fathered by saline-exposed sires, and dams carrying those pups had significantly longer gestations than those carrying pups of alcohol-using sires. More runts were born to the alcohol-sired group, and more pups in that group died over the next three weeks than in the saline-sired group. Significantly more pups in the saline-sired group achieved such developmental milestones as surface righting, clinging, the tail-pull reflex, rotation, linear movement and climbing an inclined surface earlier than did alcohol-sired pups. As adults, animals from the alcohol-sired group showed significantly less risk assessment behavior and longer latencies to such behaviors as stretched attention, flatback, freezing and defensive burying than did the saline-sired animals. Alcohol-sired animals contacted the stimulus object in the risk assessment test significantly sooner and more often than did the saline-sired group. In tests of aggression, alcohol-sired male offspring showed more frequent aggressive behaviors such as on-top, lateral attacks and jump-attacks, and significantly fewer defensive/fearful behaviors such as piloerection, tail rattling and jump-escape. This pattern of results suggests that exposure of the sire to one acute dose of alcohol before insemination caused some early developmental delays and that alcohol-sired animals are less fearful and more aggressive as adults than saline-sired animals.

Noradrenergic facilitation of shock-probe defensive burying in lateral septum of rats, and modulation by chronic treatment with desipramine

We have previously shown that acute stress-induced release of norepinephrine (NE) facilitates anxiety-like behavioral responses to stress, such as reduction in open-arm exploration on the elevated-plus maze and in social behavior on the social interaction test. Since these responses represent inhibition of ongoing behavior, it is important to also address whether NE facilitates a response that represents an activation of behavior. Correspondingly, it is unknown how a chronic elevation in tonic steady-state noradrenergic (NA) neurotransmission induced by NE reuptake blockade might alter this acute modulatory function, a regulatory process that may be pertinent to the anxiolytic effects of NE reuptake blockers such as desipramine (DMI). Therefore, in this study, we investigated noradrenergic modulation of the shock-probe defensive burying response in the lateral septum (LS). In experiment 1, shock-probe exposure induced an acute 3-fold increase in NE levels measured in LS of male Sprague-Dawley rats by microdialysis. Shock-probe exposure also induced a modest rise in plasma ACTH, taken as an indicator of perceived stress, that returned to baseline more rapidly in rats that were allowed to bury the probe compared to rats prevented from burying by providing them with minimal bedding, indicating that the active defensive burying behavior is an effective coping strategy that reduces the impact of acute shock probe-induced stress. In experiment 2, blockade of either α 1- or β-adrenergic receptors in LS by local antagonist microinjection immediately before testing reduced defensive burying and increased immobility. In the next experiment, chronic DMI treatment increased basal extracellular NE levels in LS, and attenuated the acute shock probe-induced increase in NE release in LS relative to baseline. Chronic DMI treatment decreased shock-probe defensive burying behavior in a time-dependent manner, apparent only after 2 weeks or more of drug treatment. Moreover, rats treated chronically with DMI showed no significant rise of plasma ACTH in response to shock-probe exposure. Thus, acute stress-induced release of NE in LS facilitated defensive burying, an active, adaptive behavioral coping response. Chronic treatment with the NE reuptake blocker and antidepressant drug DMI attenuated acute noradrenergic facilitation of the active burying response, and also attenuated the level of perceived stress driving that response. These results suggest that long-term regulation of the acute modulatory function of NE by chronic treatment with reuptake blockers may contribute to the mechanisms by which such drugs exert their anxiolytic effects in the treatment of stress-related psychiatric conditions, including depression and anxiety.

Ontogeny of sex differences in defensive burying behavior in rats: effect of social isolation

The aim of the present experiments was to clarify sex differences in socio-developmental factors that affected defense behavior in rats. Sex differences in the defensive burying behavior of rats, and related social factors, were explored in three developmental stages: juvenile, puberty, and adult; 30, 50, and 80 days of age, respectively. The duration of burying, digging into bedding material, stretch-attend postures, and crouch/freezing were measured in a shock-prod test. For males, the duration of burying was longer in the juvenile and pubertal stages than in adulthood. For females, no age differences in the duration of burying were found. Males showed longer burying durations than females in both the juvenile and pubertal stages. For both sexes, the highest duration of digging was found in the juvenile stage, and females showed longer durations of digging than males. Both male and female rats isolated during the juvenile stage, from 26 to 40 days of age, showed smaller durations of burying behavior compared to pair-reared rats. This effect of juvenile isolation was maintained among both adult males and females even when they were returned to pair rearing after isolation. Isolation during adulthood, from 66 to 80 days of age, increased burying behavior in males, but decreased it in females. The durations of digging, stretch-attend postures, and crouch/freezing were not affected by isolation. The decrease in defensive burying and its increase resulting from isolation in adult male rats, suggest that the emergence of adult-like social relationships in males suppressed the duration of burying. Male and female rats isolated during the juvenile stage maintained lower levels of burying, suggesting that social experience as juveniles is important for the emergence of defensive burying behavior.

Activational levels of androgens influence risk assessment behaviour but do not influence stress-induced suppression in hippocampal cell proliferation in adult male rats

Adult male, but not female, rats demonstrate a suppression in hippocampal cell proliferation in response to an acute predator odour stress. The present study examined the effect of activational levels of androgens on stress-induced changes in hippocampal cell proliferation and defensive and non-defensive behaviours in adult male rats. Adult male Sprague–Dawley rats were castrated and exposed to trimethylthiazoline (TMT, the main component of fox feces). Androgen status did not significantly affect TMT-induced suppression in hippocampal cell proliferation or expression of defensive burying. However, castrated males did not show an increase in duration of stretch attends (a risk assessment behaviour) in response to TMT. The results of this study suggest that activational levels of androgens in the male rat do not directly regulate the sex difference in stress-induced suppression of hippocampal cell proliferation but do regulate risk assessment behaviour.

Endocannabinoids modulate stress‐induced suppression of hippocampal cell proliferation and activation of defensive behaviours

The endocannabinoid system has been shown to regulate both the hypothalamic-pituitary-adrenal (HPA) axis and emotionality. The present experiment was designed to examine whether pharmacological modulation of the endocannabinoid system would affect the suppression of hippocampal cell proliferation and increase in defensive behaviours seen following exposure to predator odour (trimethylthiazoline; TMT) stress. Rats were administered either an endocannabinoid uptake inhibitor (AM404; 2 mg/kg) or a cannabinoid CB1 receptor antagonist (AM251; 5 mg/kg) 30 min prior to exposure to TMT. Exposure to TMT reduced cell proliferation in the dentate gyrus and increased the expression of defensive burying. Administration of AM404 significantly inhibited defensive burying, and attenuated the reduction in cell proliferation in response to TMT exposure. Administration of AM251 alone significantly increased cell proliferation; however, pretreatment with AM251 prevented neither the stress-induced suppression of cell proliferation nor the stress-induced increase in behavioural responses. These results support previous research demonstrating that augmentation of endocannabinoid signalling can suppress stress-responsive systems. They also suggest that endocannabinoids may play a complex role in the regulation of neurogenesis via cell proliferation in the hippocampus.

Ethological comparison of the effects of a bovine α s1-casein tryptic hydrolysate and diazepam on the behaviour of rats in two models of anxiety

A bovine α S1-casein tryptic hydrolysate was previously demonstrated to display an anxiolytic-like activity in the conditioned defensive burying and in the elevated plus-maze models when i.p. injected. The present study assessed the anxiolytic-like effects of this tryptic hydrolysate after an oral administration in rats faced to the same behavioural situations using diazepam as a reference. In a first experiment, the behavioural effects of the hydrolysate in the conditioned defensive burying test were investigated at doses ranging 5–50 mg/kg. The results showed that the minimal dose required to elicit an anxiolytic-like activity is 15 mg/kg. In a second experiment, the α S1-casein tryptic hydrolysate (15 mg/kg, p.o.) was demonstrated to display an anxiolytic-like activity similar to diazepam (3 mg/kg, p.o.) in the conditioned defensive burying test and the elevated plus-maze. However, the ethological analysis of behaviour indicated that this hydrolysate has a different activity compared to diazepam. While diazepam induced a disinhibition state in rats, possibly related to the risk-taking behaviour observed after a benzodiazepine ingestion in humans, the tryptic hydrolysate did not display such a side effect. These results suggest that the mechanism of action of the bovine α s1-casein tryptic hydrolysate may differ from that of diazepam.

Anxiolytic-like effects of nociceptin/orphanin FQ in the elevated plus maze and in the conditioned defensive burying test in rats

Different reports suggest that nociceptin/orphanin FQ (N/OFQ) may have either anxiolytic- or anxiogenic-like effect in rodents. Since N/OFQ elicits hypolocomotion, which undergoes rapid tolerance, and hypolocomotion may be associated to emotional consequences, the present study was designed to investigate the effect of N/OFQ on anxiety after development of tolerance to its hypolocomotor effect. The effect of single or double intracerebroventricular (i.c.v.) injection of N/OFQ was evaluated on anxiety-related behaviors in rats, in the elevated plus maze (EPM) and conditioned defensive burying (CDB) tests. After single administration, N/OFQ displayed an anxiogenic-like pattern of response on the elevated plus maze but hypolocomotion was also observed. Conversely, in the CDB test, N/OFQ induced a clear-cut anxiolytic pattern. To produce tolerance to N/OFQ-induced hypolocomotion the peptide was administered by two i.c.v. injections separated by 120 min; in these conditions it decreased the expression of anxiety-related behaviors in both tests without affecting locomotor activity. The nociceptin/orphanin FQ peptide (NOP) receptor antagonist UFP-101 significantly reduced the effects of N/OFQ to control values in either tests. Corticosterone levels were significantly increased after a single N/OFQ administration (not in a dose-dependent manner) but this increase did not reach significance after double administration (1 nmol/rat). Our results support the idea that N/OFQ may act as an anxiolytic-like agent in the rat; the apparent anxiogenic-like effect observed following its single administration in the EPM may be consequent to its effect on locomotion.

The acute and long-term neurotoxic effects of MDMA on marble burying behaviour in mice

When mice are exposed to harmless objects such as marbles in their cage they bury them, a behaviour sometimes known as defensive burying. We investigated the effect of an acute dose of MDMA (èecstasy') and other psychoactive drugs on marble burying and also examined the effect of a prior neurotoxic dose of MDMA or p-chloroamphetamine (PCA) on burying. Acute administration of MDMA produced dose-dependent inhibition of marble burying (EC50: 7.6 micro mol/kg). Other drugs that enhance monoamine function also produced dose-dependent inhibition: methamphetamine PCA paroxetine MDMA GBR 12909 methylphenidate. None of these drugs altered locomotor activity at a dose that inhibited burying. A prior neurotoxic dose of MDMA, which decreased striatal dopamine content by 60%, but left striatal 5-HT content unaltered, did not alter spontaneous marble burying 18 or 40 days later. However, a neurotoxic dose of PCA which decreased striatal dopamine by 60% and striatal 5-HT by 70% attenuated marble burying 28 days later. Overall, these data suggest that MDMA, primarily by acutely increasing 5-HT function, acts like several anxiolytic drugs in this behavioural model. Long-term loss of cerebral 5-HT content also produced a similar effect. Since this change was observed only after 28 days, it is probably due to an adaptive response in the brain.

A behavioural investigation of ciprofloxacin and ofloxacin in the rat

The fluoroquinolone antibacterial compounds have been associated with a variety of CNS adverse effects in humans including agitation, restlessness and even convulsions. The objective of this study was to investigate whether the fluoroquinolones namely ciprofloxacin (CIP) and ofloxacin (OFL) have any behavioural effects in male Sprague Dawley rats. Two doses of FQ were studied (40 mg/kg and 80 mg/kg of OFL and 20mg/kg and 40 mg/kg of CIP). We used four tests namely the pentobarbital induced sleeping time test, open field test (OFT), social interaction test (SIT) and the conditioned defensive burying test CDBT). All the drugs were administered via the i.p route. In the OFT, SIT and CDBT the test groups were compared with a positive control group which received Chlordiazepoxide (CDZ) (10 mg/kg). In pentobarbital sleeping time test the control group received 35 mg/kg of pentobarbital. The results showed that both CIP and OFL treated groups attenuated the sleeping time induced by pentobarbital. However neither of the drugs affected behaviour in OFT, SIT and CDBT whereas The CDZ treated group demonstrated an anxiolytic effect. The project was funded by the Department of Pharmacology, NUIG.

Exposure to RepetitiveVersusVaried Stress during Prenatal Development Generates Two Distinct Anxiogenic and Neuroendocrine Profiles in Adulthood

Early life experiences can shape brain function and behavior in adulthood. The present study sought to elucidate the effects of repetitive, predictable vs. varied, unpredictable prenatal stress on sexually dichotomous neuroendocrine and anxiety-related behavioral responses in adult offspring. Rat dams were exposed repeatedly during the last week of pregnancy to no stress, only restraint stress [prenatal stress (PS)-restraint], or a randomized sequence of varied stressors (PS-random), and several behavioral and endocrine measures were assessed in adult male and female offspring. Repeated exposure to the same stressor (restraint) generated the most robust changes, including increased anxiety-related behaviors (both passive, measured on the elevated plus maze, and active, measured using defensive burying tests), a delayed and prolonged hypothalamic-pituitary-adrenal (HPA) axis response to stress in female offspring. Conversely, PS-restraint males showed no changes in anxiety-like behavior and had elevated basal ACTH and a blunted HPA response to stress; consistent with attenuated HPA responsivity was an increase in glucocorticoid receptor immunoreactivity in the hippocampus, suggesting increased negative feedback on the HPA axis in these animals. Prenatal exposure to a varied, unpredictable pattern of stressors did not have as much effect on HPA function, with most neuroendocrine measures residing intermediate to PS-restraint and control animals within each sex. Gonadal steroids were altered independent of the type of prenatal stress, but changes were measurable only in males (lower testosterone). The present data exemplify the differential sensitivity of the developing nervous and endocrine systems to stress, depending on not only gender but also the nature of the stressful experience endured by the mother during pregnancy.

Differential progesterone effects on defensive burying and forced swimming tests depending upon a gradual decrease or an abrupt suppression schedules

A single dose of progesterone reduces the cumulative time in the defensive burying test and the immobility in the forced swim test, whereas the abrupt suppression of repeated doses increases the anxiety indicators. Whether anxiety and despair indicators reduce by a gradually decreased schedule of progesterone is unknown. Therefore, we subjected adult ovariectomized Wistar rats to open field, defensive burying and forced swim tests. One group received a constant schedule of progesterone (0.50 mg, daily), abruptly suppressed (AS) after five days. Another group received a gradual reduction schedule of progesterone (GR: 0.84, 0.67, 0.50, 0.33, 0.17 mg, each day). Control group received vehicle (VEH). The GR group displayed similar crossing in the open field test as the VEH group ( F 2,19 = 8.78, p < 0.002), but also the shortest cumulative time in defensive burying ( F 2,28 = 13.3, p < 0.0001) and the shortest time in freezing ( F 2,24 = 6.39, p < 0.006). In the forced swim test, the GR group displayed the shortest immobility time ( F 2,19 = 12.1, p < 0.0005), the lowest number of immobility periods ( F 2,19 = 4.26, p < 0.03) and the longest latency to the first period of immobility ( F 2,1 = 4.06, p < 0.03). It is concluded that a gradually reduced schedule of progesterone reduces anxiety and despair in the Wistar rat.

Administration of the galanin antagonist M40 into lateral septum attenuates shock probe defensive burying behavior in rats

Galanin (GAL) has been implicated in modulating anxiety, although a precise role remains unclear. Previous studies revealed anxiolytic effects, anxiogenic effects, or no effect, depending on the test, brain region, route of drug administration and context. We have shown previously that microinjection of the GAL antagonist M40 into central amygdala blocked an anxiolytic response to acute stress on the elevated plus maze when rats were pretreated with yohimbine, suggesting an anxiolytic effect of GAL. By contrast, we also showed that microinjection of M40 into the lateral bed nucleus of the stria terminalis attenuated anxiety-like behavioral responses to stress on the plus maze and social interaction tests, implying an anxiogenic effect for GAL. The behavioral response to stress on both these tests is a reduction of an ongoing behavior (open-arm exploration or social interaction, respectively). To better understand the anxiety-modulating role of GAL, it is also important to ascertain its effect on a response that represents an activation rather than suppression of behavior. Thus, in this study, we investigated an active behavioral response to acute stress in rats, the shock-probe defensive burying response. Bilateral microinjections of M40 into lateral septum (LS), a region important to this response and innervated by GAL, dose-dependently decreased burying without affecting immobility. No change was seen in hindpaw withdrawal latency on a thermosensitivity assay, suggesting that the reduction in burying behavior was not attributable to changes in cutaneous pain sensitivity. These results indicate that in LS, GAL facilitates the active anxiety-like behavioral response on the defensive burying test, similar to its facilitatory effect on anxiety-like stress-induced suppression of behavior in the lateral bed nucleus. These results highlight the fact that, rather than a unified system-like role in modulating anxiety, the effects of GAL can be either facilitating or attenuating, and are region-specific, context-specific and response-specific.

Animal Tests of Anxiety

Animal tests of anxiety are used to screen novel compounds for anxiolytic or anxiogenic activity, to investigate the neurobiology of anxiety, and to assess the impact of other occurrences such as exposure to predator odors or early rearing experiences. This unit presents protocols for the most commonly used animal tests of anxiety. The Geller-Seifter conflict test, the social interaction test, light/dark exploration, the elevated plus-maze, defensive burying, and the thirsty rat conflict. The protocols are described in terms of drug screening tests, but can be modified easily for other purposes.