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PubMed1995

Comparison of the behavioural and endocrine response to forced swimming stress in five inbred strains of rats.

Some inbred strains of rats showed behavioural differences in the forced swimming test, which is considered a putative animal model of depression. In the present work, the behavioural and physiological responses to forced swimming were studied in male and female rats of five inbred strains of rats: Brown-Norway (BN), Fischer 344 (FIS), Lewis (LEW), Spontaneously Hypertensive (SHR) and Wistar-Kyoto (WKY). Physiological measures were aimed at characterizing emotional reactivity, a very important issue which has usually been approached by studying a single endocrine system, and its relationship to the forced swimming behaviour. The four indices of reactivity to stress used were serum glucose, ACTH, corticosterone and prolactin. No behavioural differences between sexes were observed in the forced swimming test. In addition, BN and WKY rats showed passive behaviour compared with the other three strains, the FIS strain being the most active. Whereas only minor differences were found in the resting levels of the variables studied with regard to either sex or strain, pituitary-adrenal (PA) and glucose responses to 15 min forced swimming differed among sexes and strains. Stress-induced hyperglycaemia was lowest in WKY and highest in SHR, being lower in females than in males. The lowest ACTH and corticosterone responses to forced swimming were observed in LEW and the highest in FIS. Female rats showed a clearly higher PA response to stress in all strains. Prolactin response to stress was very similar between sexes and strains. It might thus be concluded that: (i) there are important inter-strain differences in the forced swimming behaviour, with no differences between sexes; (ii) the various physiological indices of emotional reactivity follow a different trend and no warranted conclusion on differences in emotional reactivity should be based upon a single endocrine system or even only upon physiological measures; (iii) we cannot be sure, therefore, whether or not there are differences in emotionality between the strains studied in spite of well-established inter-strains differences in the forced swimming behaviour.

Adrenocorticotropic Hormone↗
PubMed1996

Effects of acute and chronic cocaine administration on EEG and behaviour in intact and castrated male and intact and ovariectomized female rats.

Intact and gonadectomized male and female WAG/ Rij rats were used to study the effects of gender and gonadal hormones on the development of sensitization and tolerance to cocaine-induced changes in EEG and behaviour. The four groups of WAG/Rij rats differed in the number of spontaneously occurring spike-wave discharges: ovariectomy decreased and castration increased the number of spike-wave discharges. This confirms that testosterone has antiabsence effects and that female gonadal hormones may promote the occurrence of spike-wave discharges. Cocaine [10 and 20 mg/kg, intraperitoneally (IP)] was administered before and after chronic cocaine administration (9 days, one daily injection with 10 mg/kg) and EEG and behaviour were monitored. Cocaine strongly suppressed the occurrence of spike-wave discharges before and after chronic administration in all four groups, although the decrease was less in the intact males. Sensitization or tolerance induced by cocaine on EEG could not be established. Acute cocaine administration eliminated explorative, automatic, and passive behaviour, whereas various stereotypical activities such as uncoordinated head and body movements and head swaying emerged. Differences between groups were observed as intact males were less likely than subjects in the three other groups to engage in intense stereotyped behaviour. These data suggest that testosterone inhibits EEG and behavioural effects of acute cocaine administration. All four groups displayed less head swaying and more uncoordinated head and body movements after chronic cocaine administration, suggesting that behavioural sensitization had occurred. Differences between the four groups had faded away. Although pharmacokinetic differences in levels of cocaine and benzoylecgonine between the four groups were found, they could not easily be related to the behavioural differences between groups.

Animals↗
PubMed2004

Identifying predictors of persistent non-alcohol or drug-related risky driving behaviours among a cohort of young adults.

This study sought to identify adolescent risk factors that predicted persistent risky driving behaviours among young adults. It was part of a longitudinal study of a birth cohort (474 males and 459 females). The potential predictors were self-reported data obtained at ages 15, 18, 21 years (academic qualifications, personality, mental health, anti-social behaviour and driving behaviour). The risky driving behaviour outcomes were obtained at ages 21 and 26 years and included driving fast for thrills, taking deliberate risks for fun, excessive speed, dangerous overtaking, and close following (tailgating). Persistent risky drivers were defined as those who often, or fairly often engaged in a behaviour at both ages. A minority of males and very few females were classified as persistent risky drivers. Among the males, the factors that predicted at least one, or more of the outcomes were the personality trait of low constraint (i.e. low scores for control, harm avoidance, and traditionalism), aggressive behaviour, and cannabis dependence. These are characteristics to be borne in mind when developing programmes for young drivers that aim to deter the development of persistent risky driving behaviour.

Accidents, Traffic↗
PubMed2005

Relationships among negative and positive behaviours in adolescence.

The authors calculated binary indicators of seven positive and 23 negative behaviours for 22,898 8th and 15,828 11th grade students who participated in the Oregon Healthy Teens Survey across two school years. Relationships among these variables, using both the Jaccard measure of co-occurrence and the relative risk for each member of each variable pair, given exposure to the other, showed strong inter-relationships within, but not between, the sets of behaviours. The likelihood of negative behaviours given negative behaviours was much stronger than the likelihood of positive behaviours given positive behaviours. Positive behaviours provided little protection against the likelihood of negative behaviors.

Adolescent↗
PubMed2004

Regular voluntary exercise reduces anxiety-related behaviour and impulsiveness in mice.

We embarked on a study to delineate the behavioural changes in mice after 4 weeks of voluntary exercise. As an initial behavioural characterization, we exposed the control and exercising mice to a modified hole board and an open field test. As compared to control mice, exercising animals showed clear signs of increased behavioural inhibition (e.g. a longer latency to enter unprotected areas), suggesting increased anxiety in these animals. In addition, the exercising mice were reluctant to spend time in the open field's centre during the beginning of the 30-min open field test, but compensated for this at later times. Paradoxically, the exercising animals showed more rearings on the board of the modified hole board, indicating decreased anxiety. Thus, the behavioural inhibition seen in exercising mice is likely to represent decreased stress responsiveness at the behavioural level which can also be interpreted as reduced impulsiveness. To clarify whether voluntary exercise evolves in more or less anxiety-related behaviour, we exposed animals to the elevated plus-maze and the dark-light box, two selective tests for unconditioned anxiety. Clearly, compared to the control animals, exercising mice spent significantly more time on the open arm of the plus-maze and spent double the amount of time in the light compartment of the dark-light box. Taken together, we conclude that long-term voluntary exercise appears to result in decreased anxiety-related behaviour and impulsiveness. Thus, our observations fit into the concept that regular exercise strengthens endogenous stress coping mechanisms, thereby protecting the organism against the deleterious effects of stress.

Adaptation, Psychological↗
PubMed2005

Correlations between behaviours in the elevated plus-maze and sensitivity to unpredictable subchronic mild stress: evidence from inbred strains of mice.

This study aimed at investigating the relationship between anxiety-like and depressive-like behaviour in mice. Therefore, we assessed the behaviour of mice from eight different strains (FVB/NA, BALB/c, C57BL/6, DBA/2, 129/Sv, C3H/He, CBA and BA) confronted first to anxiety models (the elevated plus-maze and the free exploratory test) and then to tests of depressive-like behaviours (forced swim test and unpredictable subchronic mild stress). In the forced swim test, mice from the DBA/2, the BA and the C3H/He strains displayed higher immobility than mice from the 129/Sv, the BALB/c, the C57BL/6 and the CBA strains. In the subchronic mild stress, mice from the C57BL/6 and the CBA strains displayed low sensitivity when compared with mice from all the others strains. A stepwise multiple regression analysis suggests that behaviour in the elevated plus-maze is associated with the time of immobility in the forced swim test (20%) and with the susceptibility to the unpredictable subchronic stress procedure (31%). The behaviour in the free exploratory paradigm is slightly associated with behaviours in the two tests of depression. These results suggest that anxiety may be a factor contributing, among others, to the susceptibility to depressive-like behaviours.

Animals↗
PubMed2006

Behavioural effects of neonatal lesions of the medial prefrontal cortex and subchronic pubertal treatment with phencyclidine of adult rats.

According to the neurodevelopmental hypothesis of schizophrenia, early brain damage renders the brain vulnerable to adverse effects during puberty, which precipitate the disease in young adults. Animal models can be used to test this hypothesis. We investigated the potentially independent or interactive effects of neonatal (postnatal day 7) excitotoxic lesions of the rat medial prefrontal cortex (mPFC) and subchronic pubertal phencyclidine (PCP)-treatment on adult rat behaviour. Sham-lesioned (vehicle-injection) and naive (unoperated) rats served as controls. On postnatal days 42-48 rats were systemically injected with 5 mg/kg PCP or vehicle twice daily. Behavioural testing started at postnatal day 70. Rats were tested for locomotor activity (open field), anxiety (elevated plus maze), social behaviour (conditioned place preference for cage-mates), reward-related operant behaviour [progressive ratio (PR)] and spatial learning (four-arm baited eight-arm radial maze task). Nissl-stained sections revealed considerable regeneration of much of the lesioned tissue in the mPFC, however, with disturbed cytoarchitecture. Locomotor activity was increased by neonatal lesions but reduced after pubertal PCP-treatment. Neonatal lesions alone increased operant behaviour in the PR-test and reduced anxiety in the elevated plus maze. In contrast, PCP-treatment disturbed social behaviour while neonatal lesions had no effect. Different aspects of leaning and memory in the radial maze task were independently disturbed after neonatal lesions and PCP-treatment. Neonatal lesions and pubertal PCP-treatment differentially affected adult rat behaviour and no interactions were found.

Animals↗
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↗
PubMed2007

Non-cognitive behaviours in an APP/PS1 transgenic model of Alzheimer's disease.

Alzheimer's disease (AD) is characterised by progressive cognitive impairment with neuropsychiatric symptoms such as anomalous motor behaviour, depression, anxiety, weight loss, irritability and agitation. The effect of hAPP and PS1 overexpression on cognition has been well characterised in a variety of transgenic mouse models, however, non-cognitive behaviours have not been considered as systematically. The non-cognitive behaviour of the hAPP/PS1 transgenic mouse model (TASTPM) was observed at ages spanning the rapid progression of amyloid neuropathology. TASTPM transgenic mice, of both genders, exhibited decreased spontaneous motor activity, disinhibition, increased frequency and duration of feeding bouts, reduced body weight and, by 10 months, increased activity over a 24h period. In addition to the aforementioned behaviours, male transgenic mice also displayed enhanced aggression relative to wildtype controls. These data reveal previously unreported disease relevant behavioural changes that demonstrate the value of measuring behaviour in APP/PS1 transgenic models. These behavioural readouts could be useful in screening putative drug treatments for AD.

Age Factors↗
PubMed2006

Early behavioural enrichment in the form of handling renders mouse pups unresponsive to anxiolytic drugs and increases NGF levels in the hippocampus.

Early life experiences, such as early handling, can influence neural development of rodents leading to changes in physiological and behavioural reactivity to stress. These effects are likely to be mediated by changes in maternal behaviour. This study analyzed the effects of different manipulations of the rearing environment on maternal behaviour and the behavioural and physiological response to mild challenges in CD-1 mouse pups early during development. Litters underwent either 15 min of neonatal handling (H) or were exposed briefly to an unfamiliar male intruder from postnatal (PND) days 2 to 14 (MI). Both groups were compared with litters which were not manipulated (NH). Compared to NH subjects, licking behaviour in the MI group was increased only on the first day of introduction of the male intruder, while the H group showed an increase in maternal behaviour on PND 10. On PND 8, pups ultrasonic vocalizations were recorded upon treatment with an anxiolytic drug (chlordiazepoxide 0, 2, or 7.5mg/kg). Results indicate that, although there were no differences among the groups when mice were injected with vehicle, handled subjects did not reduce their calling rate following drug administration, in contrast to the NH and MI groups. Following maternal separation and novelty exposure on PND 9, levels of hippocampal NGF increased significantly only in the H group. These data suggest that active pup manipulations in the form of handling favour behavioural and neural plasticity resulting in the maintenance of a high level of arousal and in increased neurotrophin levels in response to an acute manipulation. Changes in hippocampal levels of NGF might be involved in the appraisal of subtle changes in the early social environment.

Age Factors↗
PubMed2004

Ethological validation and the assessment of anxiety-like behaviours: methodological comparison of classical analyses and structural approaches.

The research on emotional reactivity usually implies the use of standardised behavioural tests that provide a quick idea of the effect of a treatment on the reactivity of subjects to potentially dangerous situations. Many validity criteria have been considered to evaluate these tests. This validity concept supports the idea that animals' behaviour in these tests model human anxiety. Generally, those criteria repeatedly labelled as "ethological validation" refer to the analogy between animals and human in the meaning of the test situation. Although the content of the ethological validation concept is heterogeneous, it is steadily related to a fixed interpretation of the behavioural items produced in a given experimental setting. The basic assumption of such reasoning is that the behavioural items would always be expressed in the same behavioural context whatever the subject, its gender, strain or species, thoroughly asserting a predefined subjective state. Using multivariate and textual analysis, we found evidence that the "ethological validation" recourse to an a priori interpretation for a given behavioural variable may be deceptive. We defend the idea that the meaning of a behavioural variable should be restricted to the general context where it arose. Theoretical propositions and methodological options are discussed.

Animals↗
PubMed2005

Evolution of clinical behaviour in Crohn's disease: predictive factors of penetrating complications.

BACKGROUND AND AIMS: Crohn's disease is a heterogeneous entity. The Vienna Classification defines three different clinical patterns: 'non-stricturing, non-penetrating', 'stricturing' and 'penetrating'. Aim of this study was to assess the change in clinical behaviour over time and to evaluate whether an evolution towards penetrating complications can be predicted. METHODS: A total of 139 patients with non-penetrating behaviour at the time of diagnosis were included. The mean follow-up was 4.84 years (range 1-23.2 years). The clinical behaviour, according to the Vienna Criteria, was assessed at the diagnosis and at the end of follow up. Statistical analysis was performed by means of the Kaplan-Meier method and standard logistic regression analysis. RESULTS: The cumulative probability of a change in clinical behaviour was 22, 38 and 63% at 3, 6 and 12 years, respectively, and the cumulative probability of developing penetrating complications was 22, 33 and 55% at 3, 6 and 12 years, respectively. Young age at diagnosis (<40 years) and a stricturing behaviour are independent risk factors of developing major penetrating complications (internal fistula, mass or abscess): OR=6.0, 95% CI 1.1-30.5; OR=4.0, 95% CI 1.5-10.9, respectively, but not perianal disease. CONCLUSIONS: The behavioural classification of Crohn's disease is a dynamic model in which each status should be considered as not fixed but evolutive. Perianal disease should be considered a distinct pattern of penetrating behaviour.

Adult↗
PubMed2004

Ultrasound vocalisation by rodents does not correlate with behavioural measures of persistent pain.

Three well-established rodent models of somatic, visceral and neuropathic pain were used to test the hypothesis that a stress and anxiety evoked behaviour, namely ultrasound vocalisation, correlates with other well-characterised indices of pain behaviour, such as limb withdrawal and stereotypical behaviour. Persistent pain presents a significant clinical problem for which there remains relatively ineffective clinical management and animal models of pain are commonly employed to investigate the underlying pathophysiology and for pre-clinical evaluation of novel therapies. At present, the assessment of such animal models largely relies on the observation of simple reflex responses which may not entirely represent the full range of rodent pain behaviour. Therefore, additional integrated behavioural indices for the quantification of pain could improve the veracity of animal models. In stressful or harmful situations, it is thought that rodents produce ultrasound vocalisations to communicate within the social group. In this study, the number of ultrasound vocalisations (22 kHz) was measured during both evoked and ongoing pain. Ultrasound vocalisation was not associated with other pain behaviour in any of the inflammatory, visceral or neuropathic pain models examined and is therefore not a useful integrated correlate of pain behaviour.

Animals↗
PubMed2005

Do similar neural systems subserve aggressive and sexual behaviour in male rats? Insights from c-Fos and pharmacological studies.

It is a common belief that male aggressive and sexual behaviour share many of the underlying neurobiological, neurological, pharmacological and neuroendocrine mechanisms. Therefore, we studied brain activation patterns in male rat after performance of aggressive and sexual behaviour and compared serotonergic pharmacology in the same paradigms to delineate possible similarities and differences. Patterns of Fos-immunoreactivity induced by aggressive and sexual encounters of Wild-type male Brown Norway rats were studied to localise the commonly activated (functionally shared) parts of the circuitry, and the specific (functionally different) parts of the neuronal circuitry. Some brain areas (caudal medial preoptic area and medial amygdala) were commonly activated, but other areas (e.g. posterodorsal parts of the medial amygdala, rostral preoptic and premammillary hypothalamus) showed remarkably specific differences in neural activation. 5-HT(1A) receptor agonists inhibit aggressive, but stimulate male sexual behaviour, whereas 5-HT(1B) receptor agonists inhibit both types of behaviour. Selective serotonin reuptake inhibitors share comparable inhibitory effects in aggression and sexual behaviour, although only at relatively high doses. We propose that separate hard-wired neural systems exist in the brain for aggressive and sexual behaviours, modulated via hierarchically 'higher-level' brain areas that are involved in the integration (gating) of the behavioural outcome of an organism.

Aggression↗
PubMed2004

Activity patterns as a correlate for sleep-wake behaviour in mice.

Sleep-wake behaviour in mice is known to interact with various behavioural dimensions. Therefore, it is necessary to control for such dimensions when evaluating sleep in mice. The characterisation of sleep in rodents usually is based on EEG signals. Since this method demands the invasive implantation of electrodes, it cannot be integrated into general behavioural phenotyping procedures. Thus, non- or minimum-invasive methods are needed for the analysis of sleep-wake behaviour. Although physiological parameters, like for instance general locomotor activity, allow for the assessment of sleep-wake behaviour in mice, existing methods lack reliability especially in measuring stationary and three-dimensional activities. In this study, a small magnet was implanted subcutaneously near the neck muscles of mice and each movement of the magnet was registered via a sensor plate. For validation of the described method, the effects of sleep deprivation were evaluated by both the magnet and the EEG in parallel. Our results show that the data obtained via the subcutaneously implanted magnet represent a reliable and sensitive measurement of quantitative aspects of sleep-wake behaviour: spatial variation as well as stationary activities could be dissociated from sleep. Qualitative sleep characteristics were not detected. In summary, this minimum invasive method allows for the detection of quantitative alterations in sleep-wake behaviour in mice, thus, offering a useful, rapid pre-screen in animal sleep research.

Animals↗
PubMed2006

Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone levels and behaviour in two strains of laboratory mouse.

Behaviour was assessed in 32 C57BL/6JCrl and 32 C3H/HeN male mice 1 h following vasectomy; saline or meloxicam was administered 30 min prior to surgery at 5, 10, or 20 mg kg(-1). Faeces were collected 24 h prior to, and 3, 6, 9, 12, 24 h following, vasectomy for measurement of faecal corticosterone. Peak corticosterone levels were significantly higher in mice that underwent vasectomy and received saline (p<0.001) or meloxicam at 5 or 10 mg kg(-1) (p=0.021, and p<0.001, respectively) compared with normal un-operated controls. Mice that underwent vasectomy and received 20 mg kg(-1) meloxicam had peak corticosterone levels that were not different from normal un-operated mice (p=0.254). Discriminant analysis was used to identify behaviours responsible for group separation; these were summed to create two behaviour scores. Score 2 (the frequency of flinching, writhing, rear leg lift and press 2) was thought to be pain related; mice that underwent vasectomy and received saline exhibited significantly more of these behaviours than the normal controls (p=0.032), and the mice that received meloxicam (at any dose). Strain differences were observed in both the stress response to vasectomy and the behavioural changes; the C3H/HeN mice had higher pain scores (behaviour Score 2) and peak corticosterone responses than the C57BL/6JCrl mice. We have demonstrated that significant changes occur in the behaviour of mice following vasectomy, and these changes are reduced by use of meloxicam. Vasectomy elicits a rise in corticosterone levels that was only reduced by the highest dose of meloxicam.

Animals↗
PubMed2004

The effects of MDMA pretreatment on the behavioural effects of other drugs of abuse in the rat elevated plus-maze test.

Few preclinical studies have found long-term behavioural consequences of the serotonergic neurotoxicity produced by 3,4-methylenedioxymethamphetamine (MDMA). This study investigated whether pretreatment with MDMA altered the behavioural effects of other drugs of abuse. Adult male Lister hooded rats (n=10/group) were pretreated with 10 mg/kg MDMA or 1 ml/kg saline vehicle intraperitoneally every 2 h for 6 h. Fourteen days later, the behavioural effects of d-amphetamine (2 mg/kg), cocaine (10 mg/kg), ethanol (2.0 g/kg), heroin (0.5 mg/kg), or MDMA (10 mg/kg) were assessed in the elevated plus-maze test. MDMA pretreatment produced approximately 20-25% decrease in hippocampal 5-HT and 5-HIAA concentrations, and [(3)H]paroxetine binding when analysed 2 weeks later. Despite inducing neurotoxicity, this regimen had no effect upon the plus-maze behaviour induced by ethanol, heroin, and MDMA. Acutely, and independent of neurotoxic pretreatment, MDMA produced a clear anxiogenic-like behavioural profile with a reduction of open arm entries and suppression of explorative behaviours. Despite being acutely anxiogenic, pretreatment with a neurotoxic regimen of MDMA has little effect on the anxiety-related effects of other drugs of abuse. It is possible that extended time points would produce significant changes, although the available evidence suggests that the plus-maze may not be a suitable model for detection of behavioural dysfunction after neurotoxic MDMA.

Animals↗
PubMed2006

The "extent of information desired"-scale in psychiatric in-patients: a behavioural approach.

OBJECTIVE: The purpose of this study was to investigate the "extent of information desired" (EID)-scale through a behavioural approach. METHODS: Standardised interviews consisting of the EID-scale and four (half) open questions were conducted in a convenience sample of psychiatric in-patients and information seeking behaviour was measured. At the same time, socially desirable behaviour was assessed by means of Marlowe-Crowne social desirability (MCSD). RESULTS: 39 patients were interviewed. The behavioural approach yielded mixed results, but there was no correlation between EID- and MCSD-scores. DISCUSSION: From the calculated correlations information seeking behaviour is perceived as socially undesirable, whereas EID-scores seem unaffected by social desirability. CONCLUSION: It is difficult to define independent variables which would reflect information seeking behaviour. The ones we used might have been confounded. We found a correlation between the EID-scale used and the information seeking behaviour, without a strong correlation with social desirability. PRACTICE IMPLICATIONS: The EID-scale used may predict patients' desire for information within a well-defined clinical context. The step to validation requires more robustness of the research model and a better profiling of patients.

Adolescent↗