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PubMed1992

Inhibition of catecholamine synthesis depresses behavior of rats in the holeboard and forced swim tests: influence of previous chronic stress.

Catecholaminergic pathways in the brain are activated during stress and are presumably involved in the control of physiological and behavioral changes triggered by stress. When repeatedly stressed, adaptive changes have been observed in catecholaminergic activity in the brain. In the present experiment, it was assessed whether or not chronic exposure to immobilization (IMO) altered the influence of catecholamines on behavior in the holeboard and forced swim test by administering alpha-methyl-p-tyrosine (an inhibitor of catecholamine synthesis). Adult Sprague-Dawley rats were used. Chronic stress amortiguated the inhibitory effect of acute IMO on some but not all behaviors in the two tests. Whereas previous chronic IMO exacerbated the effects of the drug on struggling and immobility in the forced swim test, no change in response to the drug as a consequence of chronic IMO was observed in the holeboard test. The present data suggest that chronic IMO-induced changes in the catecholaminergic control of some behaviors might be related to depression-like states in rats. The actual physiological meaning of these changes and the specific receptors involved remain to be elucidated.

Animals↗

PubMed1994

Ethopharmacological analysis of rat behavior on the elevated plus-maze.

Behavioral categories were measured in rats left on an elevated plus-maze for 5 min, in addition to the traditional measures. Four independent factors emerged from a factor analysis. The variables that loaded highly and positively on Factor 1, seemingly related with anxiety, were: number of entries onto open arms, time spent on open arms, percentage of open/total arm entries, percentage of time on open arms, scanning over the edge of an open arm, and open arm end-exploring. The time spent on enclosed arms loaded highly, but negatively on the same factor. Risk-assessment from an enclosed arm also loaded negatively on Factor 1. Number of enclosed arm entries, total number of arm entries and rearing loaded highly on Factor 2, probably related to motor activity. However, the total number of entries also loaded on Factor 1, being thus a mixed index. Similarly, the number of open arm entries loaded on both Factors 1 and 2. As expected, the variables having high loads on Factor 1 were changed to one direction by administration of two anxiolytics (nitrazepam and midazolam) and to the opposite direction by two anxiogenic drugs (pentylenetetrazol and FG 7142). Such pattern of drug effects was not observed with the remaining variables.

Animals↗

PubMed1992

Behavioral effects of atriopeptin in rats.

High densities of atriopeptin-immunoreactive fibers and of highly specific and selective atriopeptin receptor sites are present in brain areas involved in animal behavior. The possible influence of these peptides on behavior was thus investigated in adult rats. The intracerebroventricular injection of atriopeptin II modified male sexual behavior (reduction in mount latency) at the dose of 5 micrograms/animal; lower and higher doses were ineffective. Open-field behavior was also modified by i.c.v. atriopeptin II at the doses of 5 and 10 micrograms/rat, which induced an increase in the number of external and internal crossings and of external rearings. Finally, in fasted rats, atriopeptin II, at the dose of 10 micrograms/rat, significantly increased the amount of food intake 30 and 60 min after injection. These findings indicate that atriopeptins may modify different animal behaviors.

Animals↗

PubMed1982

Different reaction patterns in individually and socially reared rats during exposures to novel environments.

Individually and group-reared male rats were behaviourally compared after various periods of different housing, (i) during a first exposure to the new environment, and (ii) after habituation (two repetition trials) to the situation, during a fourth exposure in a slightly modified test-box. Compared to group-housed controls an elevated locomotor activity upon the first exposure and a reduced reaction in response to the slight modifications were found in individually housed rats.

Aging↗

PubMed1988

Graded increases in brain GABA: differential effects on feeding and other behaviours in rats.

Elevations of brain gamma-aminobutyric acid (GABA) induced by inhibitors of GABA transaminase (GABA-T) are known to induce a number of functional effects including depression of food intake. The aim of the present study was to determine the brain GABA elevation threshold for changes in feeding and several other behaviours, in an effort to clarify whether feeding changes might be secondary to other functional deficits. To this end, various doses of the GABA-T inhibitors ethanolamine-o-sulfate (EOS) and gamma-vinyl GABA (GVG) were injected intracisternally and effects on whole brain GABA, food and water intake, open field activity, catalepsy indices, pain sensitivity, and core temperature were assessed 24 h later. Progressive increases in brain GABA levels were found to differentially affect the responses studied. At the low end of the continuum, significant decreases in feeding behaviour were associated with relatively modest increases in brain GABA (40-60%). At higher levels of GABA elevation (greater than 100%), changes in motoric functions and rectal temperature became apparent. At still higher levels (greater than 200% increases in brain GABA), significant antinociceptive effects were detected. These results support the notion that feeding decreases induced by low doses of GABA-T inhibitors may reflect a fairly specific effect on appetite mechanisms, but also indicate that with increasingly higher doses several other deficits are likely to contribute to the overall decrease in food intake.

4-Aminobutyrate Transaminase↗

PubMed1990

Thymopentin antagonizes stress-induced changes of GABA/benzodiazepine receptor complex.

Intraperitoneal administration of thymopentin, a thymopentin II-derived pentapeptide, had no stable and evident effect in the two anxiety models (elevated plus-maze and licking-conflict test) studied. However, in the elevated plus-maze test thymopentin antagonized the behavioral effects of DMCM, a beta-carboline derivative with anxiogenic properties. Further, it was demonstrated that the licking-conflict test procedure itself produced a significant elevation of plasma corticosterone levels, increased the number of [3H]flunitrazepam and decreased the number of [3H]muscimol binding sites in rat hippocampus. The forced-swimming stress similarly to the licking-conflict test also caused an increase in hippocampal [3H]flunitrazepam binding sites. Although ineffective behaviorally in the tests for anxiety, thymopentin pretreatment effectively reversed the changes in corticosterone levels caused by the licking-conflict test. Moreover, it normalized the changed number of benzodiazepine and GABA receptors after stressful stimuli. It is well known that not all anxiolytic drugs (i.e. buspirone) are equally active in behavioral tests for anxiety. According to our data we propose that thymopentin has stress-protective activity. As in vivo and in vitro thymopentin did not change [3H]-flunitrazepam and [3H]muscimol binding, the direct effect of this peptide on the GABA-benzodiazepine-Cl- ionophore receptor complex is unlikely. The action of this peptide on GABA release and/or metabolism can be suggested.

Animals↗

PubMed1994

Evidence for mnemotropic action of cholecystokinin fragments Boc-CCK-4 and CCK-8S.

Memory-modulating and reinforcing effects of the cholecystokinin (CCK) fragments, CCK-8S and Boc-CCK-4, after systemic application in rats were investigated. Habituation to the novelty of environmental stimuli was used to test for mnemonic effects using two different tasks (rearing behavior in an open field; head-dips in a hole-board). Immediate posttrial administration of CCK-8S and Boc-CCK-4 resulted in a reduction of rearing and head-dip behavior during testing, indicative of enhanced habituation and, thus, facilitation of memory. In contrast, administration of CCK-8S and Boc-CCK-4 with a delay of 2.5 or 5 h after training or pretrial injection of CCK-8S did not enhance habituation. No evidence for reinforcing or aversive properties of CCK-8S and Boc-CCK-4 was observed in a conditioned place preference task. In summary, the results indicate memory-enhancing effects of peripherally, posttrial-administered CCK-8S and Boc-CCK-4.

Amino Acid Sequence↗

PubMedDate not supplied

L-glutamate abolishes differential responses to alcohol deprivation in mice.

Hybrid mice produced by crossing CBA and C57BL lines were deprived of alcohol for three days after prolonged prior access. Subsequently, when access was first given to a flavored 30% alcohol solution, about half of the mice showed a greatly elevated rate of drinking during the first 1.5 h, characteristic of the alcohol-deprivation effect (ADE), but other mice showed no increase. Repeating the test three weeks later showed that having or lacking an ADE is a stable group characteristic. Behavioral differences were found on cross-maze and slip funnel tests between mice that had an ADE and those that lacked it. Topical application of L-glutamate to the frontal cortex prevented the subsequent elevation of alcohol drinking during the first 1.5 h after deprivation but did not alter drinking during the remaining 22.5 h. L-glutamate treatment also affected those cross-maze behaviors found to be related to the ADE. The results suggest that frontal cortex neurons sensitive to L-glutamate are necessary for the ADE and that comparisons between hybrid mice having and lacking an ADE might be used for determining the neuronal mechanisms responsible for the effect.

Alcohol Drinking↗

PubMedDate not supplied

An ethologist's approach to behavioural toxicology.

Ethology, the biology of behaviour, is briefly introduced, and a review is presented of two ethological methods applied to toxicology. (1) When elements in the behaviour of rats in a social situation are objectively observed, chemically-induced changes in several kinds of behaviour can be detected at low doses. Changes are specific and repeatable in long-term experiments. Effects of nicotine at a 'smoking' dose, or trichloroethylene at the Threshold Limit Value, were reversible; limited tolerance developed to methyl mercury dicyandiamide. (2) An 'Exploration-Thirst' method is simple enough for use as a screen. It was compared with conventional toxicological methods for 30 compounds in routine screening (20 acute intraperitoneal, 10 subacute inhalation). Both ethological methods are sensitive enough to estimate 'no-effect' doses. They also distinguish non-specific toxic effects (consistent with the animal's equivalent of 'feeling ill') from various more specific CNS effects comparable to those of human experience.

Animals↗

PubMed2004

Further evidences that risk assessment and object exploration behaviours are useful to evaluate emotional reactivity in rodents.

In this study, we tested the ability of risk assessment and exploration behaviours to emphasise PH effects. Indeed, postnatal handling (PH) decreases emotional reactivity in rats but inconsistent behavioural results can be observed and may be due to false negative (i.e. existing effects are not detected). Risk assessment behaviours were measured in the elevated plus maze, in the free exploration paradigm and in the open field. In addition, we measured object exploration behaviours towards familiar/new objects in the open field. PH increased general activity in the elevated plus maze and in the free exploration paradigm and risk assessment behaviours allowed demonstrating that these effects were specific to emotional reactivity. In the open field, PH increased object exploration as early as first exposition while general activity was unaffected. PH also decreased behavioural inhibition in response to the introduction of a novel object. On the whole, our results show that risk assessment and object exploration behaviours are valuable tools to measure more precisely emotional reactivity in rodents. This reinforces the idea that these behaviours should be used more frequently in order to avoid false negative when emotional reactivity changes are expected in unconditioned conflict tests.

Analysis of Variance↗

PubMed2004

Comparison of 6-hydroxydopamine-induced medial forebrain bundle and nigrostriatal terminal lesions in a lateralised nose-poking task in rats.

The nigrostriatal degeneration underlying Parkinson's disease (PD) is commonly modeled in experimental animals by injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Although a wide variety of simple behavioural screens exist to assess the impact of such dopamine lesions, more complex tasks that assess multiple parameters of an animal's performance may provide a more sensitive measure of the resulting functional impairment. This study assessed the performance of two unilateral lesion models of PD in a lateralised nose-poking task in the nine-hole box test apparatus. This task assesses the accuracy and speed of movements to either side of a rats' head, as well as a number of errors of performance. Rats with complete unilateral dopamine depletion (induced by injection of 6-OHDA into the medial forebrain bundle (MFB)) attempted fewer trials and committed more procedural errors than controls. They developed a marked ipsilateral responding bias, with a reduced accuracy for contralateral stimuli. They were also slower to react to contralateral stimuli and to complete movements bilaterally. Rats with unilateral nigrostriatal terminal lesions (induced by multiple injections of 6-OHDA in the striatum) developed a similar pattern of deficits, but they were significantly less impaired and spontaneously recovered to pre-operative levels by 4 months post-lesion. This experiment confirms that the lateralised nose-poking task may be a powerful tool for assessment of the nature of deficit and recovery in rats with complete but not partial unilateral dopamine lesions.

Adrenergic Agents↗

PubMed2005

Altered behavioural response to acute stress in mice lacking cellular prion protein.

Although many studies have investigated the function of cellular prion protein (PrPc), its physiologic role remains elusive. PrPc null mice have been reported to develop normally and to show normal performance in most behavioural tests. In the present study we investigated whether this also holds true after episodes of acute stress. PrPc gene ablated (Prnp0/0) and wild-type mice were subjected to restraint stress, electric foot shock, or swimming and compared with non-stressed animals. Immediately after the stressful situation, the anxiety levels and locomotion of the animals were measured using plus-maze and open-field tests. Among non-stressed animals, there was no significant difference in performance between Prnp0/0 and wild type animals in either test. However, after acute stress provoked by a foot shock or a swimming trial, Prnp0/0 animals showed a significant decrease in anxiety levels when compared with control animals. Moreover, after the swimming test, knockout mice presented decreased locomotion when compared to wild-type mice. Because of this observation, we also assessed both types of mice in a forced swimming test with the objective of better evaluating muscle function and found that Prnp0/0 animals presented reduced forced swimming capacity when compared to controls. As far as we know, this is the first report suggesting that cellular prion protein is involved in modulation of anxiety or muscular activity after acute psychic or physical stress.

Analysis of Variance↗

PubMed2005

Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

Analysis of Variance↗

PubMed2006

Enhanced context-dependency of object recognition in rats with hippocampal lesions.

Object recognition memory was assessed on a novel-object preference (NOP) task in rats with lesions of the hippocampal formation (HPC). The learning and test phases of NOP trials occurred in either the same context or in different contexts. When the learning and test contexts were the same, rats with HPC lesions performed like control rats, displaying a significant tendency to investigate a novel object more than a familiar sample object. When the test occurred in a context that was familiar but different from the learning context, performance was unaffected in control rats, but rats with HPC lesions no longer discriminated between the objects, and therefore showed no evidence of recognizing the sample object. When the test context was unfamiliar, novel-object preference in control rats was attenuated but still above chance levels, whereas rats with HPC lesions did not show a preference. The data suggest that the HPC is not critical for encoding or retrieving conjunctive representations of the context in which incidental learning occurs, whereas it plays an essential role in recognition of objects that are subsequently encountered in different contexts.

Animals↗

PubMed2006

Models of anxiety: responses of rats to novelty in an open space and an enclosed space.

Exposure to novelty has been shown to induce anxiety responses in a variety of behavioural paradigms. The purpose of the present study was to investigate whether exposition of naïve rats to novelty would result in a comparable or a different pattern of responses in an open space versus enclosed space with or without the presence of an object in the centre of the field. Lewis and Wistar rats of both genders were used to illustrate and discuss the value and validity of these anxiety paradigms. We examined a wide range of measures, which cover several aspects of animals' responses. The results of this study revealed significant differences between the behaviour of animals in an open space and in the enclosed space. It also revealed significant differences in animal's responses to the presence and absence of an object in the open space and in the enclosed space. In the enclosed space, rats spent most of their time in the outer area with lower number of exits and avoided the object area except when there was an object, while in the open space rats displayed frequent short duration re-entries in the outer area and spent longer time in the object area in presence of an object. The time spent in the inner area (away from the outer area and the object area) was significantly longer and the number of faecal boli was significantly higher in the open space than in the enclosed space. In the present report, we will discuss the fundamental differences between enclosed space and open space models, and we will examine some methodological issues related to the current animal models of human behaviour in anxiety. In the enclosed space, animals can avoid the potential threat associated with the centre area of a box and chose the safety of walls and corners, whereas, in the open space animals have to avoid every parts of the field from which there was no safe escape. The response of animals to novelty in an open space model appears more relevant to anxiety than in an enclosed space. The present studies revealed no correlations between the measures of behaviour in enclosed space and the measures of behaviour in open space, which suggest that these two models do not involve the same construct. Our results suggest that the enclosed space model involves avoidance responses while the open space model involves anxiety responses. The open space model can be very useful in understanding the underlying neural mechanisms of anxiety responses, and in assessing the effects of potential anxiolytic drugs.

Adaptation, Psychological↗

PubMed2006

Relationship of delay aversion and response inhibition to extinction learning, aggression, and sexual behaviour.

Impulsivity is an important symptom of many psychiatric disorders, and can be divided into two subtypes: response inhibition deficits and delay aversion. In the present study, we investigated the relationship between delay aversion and response inhibition, both to each other and to locomotion, extinction of conditioned responses, sexual behaviour, and aggressive behaviour. To that end, we quantified the behaviour of 24 rats in several tests. To measure response inhibition, rats were trained in a stop-signal task. In this operant task, rats were rewarded food if they inhibited execution of a response after presentation of an audible stop-signal. Delay aversion was measured in an operant task in which rats made a choice between a small, immediately available reward and a large reward available after a delay. The results showed that delay aversion and response inhibition were independent. Responses during extinction and various measures of aggressive behaviour were positively correlated to delay aversion. The speed of go-trials in the stop-task was correlated to non-aggressive behaviour. We conclude that the role of response inhibition in various behaviours is small, but delay aversion in particular contributes to several other behaviours, such as aggressive behaviour and extinction.

Aggression↗

PubMed2006

Effects of genetic background and environmental novelty on wheel running as a rewarding behaviour in mice.

Recent studies suggest running wheel activity to be naturally rewarding and reinforcing; considering the shared neuro-behavioural characteristics with drug-induced reward situations, wheel running behaviour gains interest as a tool to study mechanisms underlying reward-sensitivity. Previously, we showed that wheel running has the potential to disrupt the daily organization of home cage behaviour in female C57BL/6 [de Visser L, van den Bos R, Spruijt BM. Automated home cage observations as a tool to measure the effects of wheel running on cage floor locomotion. Behav Brain Res 2005;160:382-8]. In the present study, we investigated the effects of novelty-induced stress on wheel running and its impact on home cage behaviour in male C57BL/6 and DBA/2 mice. Our aim was to determine whether wheel running may be used as a tool to study both genetic and environmentally induced differences in sensitivity to rewarding behaviour in mice. One group of male mice was placed in an automated home cage observation system for 2 weeks with a wheel integrated in the cage. A second group of mice was allowed to habituate to this cage for 1 week before a running wheel was introduced. Results showed a pronounced sensitising effect of novelty on the level of wheel running in C57Bl/6 mice but not in DBA mice. Overall levels of wheel running were higher in DBA/2 mice. Furthermore, wheel running affected circadian rhythmicity in DBA/2 mice but not in C57BL/6 mice. From these findings we tentatively suggest that wheel running behaviour could serve as a tool to study the interaction between genetic and environmental factors in sensitivity to rewarding behaviour in mice. As it is displayed spontaneously and easy to monitor, wheel running may be well suitable to be included in high-throughput phenotyping assays.

Analysis of Variance↗

PubMed2006

Novel object exploration in ravens (Corvus corax): effects of social relationships.

Social context has been shown to encourage, or to delay object exploration and learning. This ambiguity might be due to factors such as social relationships and personality of the individuals involved. Here, we investigated in ravens (Corvus corax) individuals' consistency in response to novel objects over development and across contexts: alone versus social. In the social setting we focussed on the effects of social relationships on social facilitation during the approach to novel objects. We tested 11 hand-raised ravens with novel objects individually at three and six months of age and in dyadic combinations at six months of age. Individuals were consistent over development and contexts in their response to different novel objects. Birds joined siblings faster to approach novel objects than non-siblings. They also spent more time sitting close to siblings than to non-siblings. In male-male dyads but not in female-female dyads, subordinates approached the novel objects significantly faster than dominant birds. In contrast, dominant males were the first to approach the novel objects in mixed-sex combinations. Hence, the effect of social context seems to depend on the social relationships towards the companions and on the combination of the sexes.

Animals↗