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D-amphetamine, cocaine and caffeine: a comparative study of acute effects on locomotor activity and behavioural patterns in rats.

Although open-field behaviour has been considered a valid and reliable index of locomotor activity in rodents, the simple measures traditionally recorded in this test do not readily allow for differentiation between compounds of the same general class, e.g. psychostimulants. The present methodology was developed to facilitate detailed and continuous observations on the behaviour of drug-treated rats. In addition to an automated (photocell) measure of general locomotor activity, ethological techniques were used to record the frequency and duration of standing, moving, sniffing, rearing, grooming, scratching, sniffing air, freezing, head-swinging and licking. A series of factor analyses was also performed in order to further characterize treatment-induced changes in the structure of behaviour. Compounds studied were d-amphetamine (0.5, 1.5, 3, 6 mg/kg), cocaine (5, 10, 20, 50 mg/kg) and caffeine (5, 10, 20, 40 mg/kg). Although all three psychostimulants increased the automated measure of general locomotor activity, cocaine (which produced the largest effects) monotonically increased general activity over the dose range tested, whereas the stimulant effects of the other two compounds were either reduced (d-amphetamine) or eliminated (caffeine) at higher doses. More detailed observations provided confirmation of the differences in effect produced by these compounds. For example, the frequency and duration of 'moving' dose-dependently increased after cocaine, while d-amphetamine and caffeine again produced bell-shaped dose-response curves. However, whereas low-intermediate doses of d-amphetamine reduced the mean duration of moving, sniffing and rearing, no such effect was observed at the highest dose tested. This finding, together with the appearance of licking in the behavioural repertoire, suggests a stereotyped character to responses seen at high doses of this compound, though neither cocaine nor caffeine induced stereotypy. As factor analyses also revealed quite different behavioural structures associated with these three drugs, present findings demonstrate that detailed observation of behaviour represents a useful approach to research on the behavioural pharmacology of psychostimulants.

Animals↗

Phamacokinetic-pharmacodynamic modelling of behavioural responses.

Drug concentrations at the site of action in studies on behavioural pharmacology, are seldom constant. Therefore, observed changes in behaviour can be due to the natural time course of behavioural processes, but equally to changes in drug concentration, and it is therefore crucial to separate the former from the latter. One solution is keeping drug concentrations constant. However, one can also exploit the variation in drug concentration caused by absorption, distribution and elimination of a drug. This is done by simultaneous measurement of drug effect and concentration, while the drug enters and leaves a biologically relevant compartment, such as blood or cerebrospinal fluid. The concept of determining concentration-effect curves in individual animals, by monitoring in parallel drug effect and changes in concentration in one single experiment, has not yet found wide application in behavioural studies. The fact that behavioural processes, like any other physiological process, change over time, may have contributed to the scarcity of pharmacokinetic-pharmacodynamic (PK/PD) studies in behavioural pharmacology. However, there are now mathematical techniques that allow PK/PD modelling even if the effect parameter changes over time or cannot be properly assessed in every instance. Here we use PK/PD modelling to characterize fear-induced ultrasonic vocalizations and the anxiolytic effect of buspirone. This approach reduces the number of animals required to assess concentration-effect relationships. More importantly, it allows the identification of differences in individual drug response over a wide range of concentrations. Consequently, we suggest that PK/PD modelling can be used as a tool to study drug-induced changes in behavioural response. An introduction in PK/PD modelling is presented.

Animals↗

Cortisol in violent suicidal behaviour: association with personality and monoaminergic activity.

BACKGROUND: According to recent theories, suicidal behaviour is associated with depressive disorders that are commonly induced by social stressors in persons with a trait-dependent vulnerability. Stressor-induced increased cortisol secretion may interfere with this vulnerability that can be defined in terms of (possibly inter-related) biological and psychological or personality-related characteristics. Delineation of such trait-like characteristics may increase the specificity in the prediction of suicidal behaviour and thus lead to new approaches to the treatment and prevention of suicidal behaviour. METHODS: Psychiatric symptomatology, personality dimensions (Cloninger's Temperament and Character), peripheral markers of serotonergic (whole blood serotonin, platelet MAO activity) and noradrenergic (plasma MHPG) activity, and urinary cortisol were measured in a random sample of patients with a history of violent suicidal behaviour and compared to those of patients without such a history. RESULTS: When compared to patients without a history of violent suicidal behaviour (n=23), patients with such a history (n=17) were characterised by higher urinary cortisol levels, a significantly lower mean score on Reward Dependence, a borderline significantly increased score on Novelty Seeking and a significantly lower mean plasma MHPG level. Urinary cortisol level correlated significantly with Reward Dependence and Novelty Seeking scores. There were no differences between patient groups regarding severity of anxiety or depressive symptomatology. No differences with regard to the biological parameters were found between patients who recently attempted suicide and those with a history of suicidal behaviour. LIMITATIONS: Limitations of this study included a relatively small number of study subjects and the use of peripheral markers to assess central neurotransmission functions. CONCLUSIONS: Violent suicidal behaviour is associated with increased cortisol secretion, a personality profile defined by low Reward Dependence (reflecting the degree of sensitivity to social stressors) and a tendency of increased Novelty Seeking (related to impulsivity and the regulation of anger), and reduced noradrenergic functioning (possibly reflecting an inability to adapt to stressors).

Adult↗

Cardiovascular and behavioural responses to psychological stress in spontaneously hypertensive rats: effect of treatment with DSP-4.

We used a model of psychological stress combining exposure to an open-field novel environment, radio-telemetric measurement of blood pressure and heart rate, and behavioural tracking analysis of behavioural parameters. All rats showed significant increases in blood pressure and heart rate for the duration of open-field exposure, with spontaneously hypertensive rats (SHR) showing markedly greater pressor responses and tachycardia when compared to either Wistar-Kyoto (WKY) or Sprague-Dawley rats (SD rats). Behavioural responses in the open-field were unrelated to the magnitude of cardiovascular responses. Open-field exposure on 4 consecutive days induced similar pressor responses and tachycardia on each day. By contrast, behavioural responses were reduced from the second day of open-field exposure. Treatment of SHR and WKY rats with DSP-4, to deplete central noradrenaline levels, did not affect cardiovascular responses in SHR, whereas WKY rats showed a trend towards inhibition. However, in WKY rats, but not SHR, DSP-4 treatment caused a marked reduction in behavioural activity in the open-field. In conclusion, these data show that: (1) SHR display marked cardiovascular hyperreactivity to psychological open-field stress when compared to two normotensive rat strains; (2) unlike behavioural responses, cardiovascular stress responses do not habituate upon repeated stress exposure; and (3) noradrenergic projections from the locus coeruleus do not appear to play a major role in cardiovascular stress responses in SHR or WKY rats, although they may be involved in behavioural responses in WKY rats.

Adrenergic Agents↗

Behavioural phenotyping of mouse mutants.

Behavioural phenotyping of mouse mutants is not a goal in itself but serves to characterise the behavioural effects of naturally occurring or experimentally induced mutations. Genetically engineered mouse mutants are valuable tools to elucidate the genetic control of behaviour and the interaction between genetic and environmental factors. However, a prerequisite for their use is the ability to assess different elements of behaviour. To this end, a battery of tests, which should be flexible enough to meet the needs of a particular study, should be used to characterise the behavioural phenotype. Detailed and extensive information about the effects of gene mutations is crucial for model building and model evaluation. Model building is an iterative process, switching between experimental data and theory formation. In order to facilitate this process and to allow comparison of results within and between laboratories, the standardisation of breeding, housing, and testing conditions is essential. The development and standardisation of sensitive, valid behavioural tests which are suited to phenotype mouse mutants is both a responsibility and a challenge to investigators of mouse behaviour.

Animals↗

Physical but not emotional stress induces a delay in behavioural coping responses in rats.

Physical stress (PS) and emotional stress (ES) have opposite long-term effects on open field behaviour. PS consisted of a repeated mild foot shock treatment, which the ES animals witnessed. PS caused a long-term decrease in locomotor activity and exploration behaviours and increased immobility. ES induced an increase in locomotor activity. These changes in open field behaviour could be the result of several factors such as increased anxiety, a shift in coping strategy or simply a change in locomotor activity. To investigate the effect of the PS and ES treatment on these separate factors, the following behavioural tests were performed: defensive withdrawal, shock prod bury, large open field and social interaction. PS animals initially showed immobility in the shock prod bury test and the large open field, while the differences measured over the entire test period were small or not present. PS did not induce differences in the defensive withdrawal and the social interaction tests. ES and control animals did not differ significantly in any of the tests. The effects of PS in the shock prod bury test in particular can be interpreted as an indication of a passive coping style. However, PS animals showed the same behaviour as controls, but started displaying the behaviour after the initial immobility response. It is concluded that neither PS nor ES affects the coping style and anxiety level of the rats. PS induces a delay in behavioural responding and ES induces locomotor activation per se. It seems that the shock prod bury test is most suitable to distinguish between exploration and coping style.

Adaptation, Psychological↗

Structure of the mouse behaviour on the elevated plus-maze test of anxiety.

The elevated-plus maze is an animal model where the behavioural repertoire of rodents is used to detect effects on anxiety. However, the structure of behaviour has not been duly discerned. The objective was to perform descriptive, sequential and principal components analyses to discern the overall structure of the mouse behaviour on the elevated plus-maze test. Behaviour was videotaped and later analyzed. Behavioural elements were encoded from an ethological point of view, being employed an 8-pattern ethogram. Stretched attend posture (SAP) and head-dippings (Dip) were split into protected (pSAP, pDip) and unprotected (uSAP, uDip) behaviours. Markovian sequential analysis revealed that sniffing is the main pattern, pSAP and pDip are highly linked 'anxiety-related' responses, and uSAP is an 'approach-avoid conflict' response usually followed by either sniffing on an open arm or closed arm entry. Principal component analysis allowed obtaining four components: (i) anxiolysis-open arm entry, pSAP, pDip and uDip; open arm entry and uDip were positively loaded, in contrast to pSAP and pDip, which were oppositely related to them; (ii) motor activity-closed arm entry, sniffing, rearing, and total arm entries; (iii) approach-avoid conflict-uSAP and negatively loaded, closed arm return; and (iv) displacement-grooming and rearing. Results suggested that open arm entry, pSAP, pDip, and uDip are the best indicators of anxiety on the elevated plus-maze. Closed arm return and uSAP are independent anxiety-related patterns, reflecting an approach-avoid conflict dimension. Results should be taken into account if the effects of drugs or CNS manipulations on Swiss mouse behaviour on the elevated plus-maze are analyzed.

Animals↗

Mild traumatic lesion of the right parietal cortex of the rat: selective behavioural deficits in the absence of neurological impairment.

Fluid impact models are widely used to study the histological and neurochemical consequences of traumatic brain injury and although behavioural consequences have also been studied, behavioural changes are often confounded by non-specific neurological deficits. In the present study we investigated behavioural effects of a unilateral mild traumatic lesion of the right lateral parietal cortex. This region is implicated in a number of basic and complex behaviors, and we therefore analyzed the performance of rats in a diverse range of behavioural procedures. The lesion had no effects on general neurological function, motor activity (activity boxes, rota-rod and paw reaching tests), habituation to a novel environment (holeboard), spatial learning ability (Morris water maze) or anxiety (elevated plus-maze). However, the lesioned animals demonstrated lower levels of exploration than the control group when novel objects were placed beneath some of the holes in the holeboard. Lesioned animals also differed from controls in their performance in passive and active avoidance procedures. In a step-through passive avoidance test the lesioned rats performed worse than the sham-operated controls, i.e. they had significantly lower entry latencies on the 2nd day. In contrast, in the active avoidance task the lesioned animals performed better than sham-operated rats, demonstrating a better ability to learn to avoid and escape from the shock. These diverse results in different tests of learning and memory, in particular the impairment in passive avoidance and the improvement in active avoidance behavior, are difficult to reconcile with a simple effect of the lesion on cognitive performance per se. The complete absence of general neurological deficits following the mild traumatic injury rules out the possibility that the observed behavioural changes reflect a non-specific impairment. These results demonstrate that mild traumatic lesion of the right parietal cortex can induce relatively selective behavioural changes that may serve to study functional recovery after trauma. However further work is required to establish the underlying deficit(s) that has led to the behavioural effects described here.

Animals↗

Associations between behavioural indicators of "stress" in weaner pigs and respiratory lesions at slaughter.

The aim of the study was to investigate associations on the individual-pig level between eight behavioural indicators of 'stress' (defined in a very general sense), in seven to eight-week old piglets four weeks after weaning and the occurrence of atrophic rhinitis (AR) and chronic pleuritis (CP) at slaughter. The study was designed as a cohort study, including 512 pigs from two commercial farms. With one exception Actinobacillus pleuropneumoniae serotype 2 (App2) infection was not associated with any of the behaviour patterns observed. Using random-effects logistic regression, weak statistical associations, positive as well as negative, were found between the performance of several behaviour patterns and the two pathological lesions. This suggests the existence of biological associations between oral behaviour patterns in young pigs and the health status later in life. However, the results were not consistent between specific oral behaviour patterns or between the two herds indicating that the associations found are either due to chance or reflect the existence of herd-specific confounders. Therefore, results based on studies within only one herd should not be generalized to other herds without care. Behavioural observations on seven- to eight-week-old piglets on the basis of the present investigation cannot be recommended for use as early predictors of AR or CP at slaughter. Further studies are needed in order to elucidate causal relations between behaviour and health.

Abattoirs↗

PGF(2alpha)-induced nest building and choice behaviour in female domestic pigs.

The domestic pig, Sus scrofa, builds a maternal nest in the day before parturition. A model for porcine nest building has been established, in which exogenously administered prostaglandin (PG)F(2alpha) is used to induce nesting behaviour in cyclic, pseudopregnant and pregnant pigs. This experiment was designed to examine the effect of PGF(2alpha) on the preferences of non-pregnant gilts for pens bedded with straw compared with bare pens. Ten 6-month-old nulliparous female pigs (gilts) were tested in an arena, which consisted of four pens (1.8mx1.7m), a neutral area (1.5mx3.4m) and a start area (1.5mx3.4m). Two of the pens contained 2kg of fresh straw and the remainder of the testing arena was devoid of straw. On the first day of testing half of the pigs were given a control intramuscular injection of 3ml 0.9% saline and the remainder were given an intramuscular injection of 15mg PGF(2alpha) and their behaviour scored for 1h after treatment. On the following day the treatments were reversed, such that each pig was given both treatments (saline or PGF(2alpha)). There was no significant effect of the order of treatment on behaviour. After saline-treatment the pigs spent most of their time in the pens containing straw (59%) and the least amount of time in bare pens (5%). In the straw pens, saline-treatment induced bouts of oronasal contact with straw of a relatively long duration (11-100s), which we interpret as foraging. In the hour after PGF(2alpha)-treatment the pigs also spent most of their time in the pens containing straw (44%) and the least amount of time in bare pens (10%), but they interacted with the straw in a markedly different way. PGF(2alpha)-treated pigs displayed bouts of oronasal contact with straw of a relatively short duration (2-10s) which, together with high frequencies of pawing at straw, lifting and carrying straw in the mouth, we interpret as nest building behaviour. Superimposed on this is the finding that gilts spend more time in the neutral areas after PGF(2alpha)-treatment than they did after saline-treatment. PGF(2alpha)-treated pigs spent most of their time engaged in nesting behaviour within the straw pens but they also gathered and deposited straw in different areas of the test arena (neutral and start areas); behaviours not seen after saline-treatment. We conclude that pigs generally prefer a pen containing straw bedding to a bare pen but that PGF(2alpha) alters the way they interact with straw, inducing behaviour similar to prepartum nest building.

Journal Article↗

Integrative animal behaviour and sociogenomics.

Integrative animal behaviour is on the rise: some behavioural neuroscientists are increasingly asking 'why', while some behavioural ecologists are starting to ask 'how'. For example, the most recent edition of Krebs and Davies' authoritative Behavioural Ecology: an Evolutionary Approach contains, for the first time, a section on mechanistic analyses of behaviour within an ecological context. This nascent synthesis can be catalysed by molecular genetic analyses of behaviours that occur in a natural context. Recent findings can provide a foundation for increased integration in the study of social behaviour, and provide the basis for an agenda for research on 'sociogenomics'.

Journal Article↗

The geography of behaviour: an evolutionary perspective.

Traditional approaches to the study of behaviour have typically assumed that behavioural patterns, especially elements of reproductive behaviour, are invariant within species. Recent research on a diversity of behavioural traits in a wide array of taxa provides evidence that genetically based geographic variation in behaviour is common. Comparisons of populations that display geographic variation in behaviour can offer substantial insight into mechanisms of adaptive divergence and constraining or generative roles of gene flow, initial stages of speciation, and the roles of phenotypic plasticity and ontogeny in determining patterns of behavioural evolution.

Journal Article↗

Health behaviours and health: evidence that the relationship is not conditional on income adequacy.

This study used Canadian data to examine whether the relationships between two health behaviours (physical activity and smoking) and two measures of health (self-perceived health status and number of chronic health conditions) are conditional on income adequacy. Studies that have investigated the manner in which socioeconomic circumstances, such as income adequacy, and health behaviours interact to influence health are few in number and characterized by inconsistent findings. In addition, there is a complete absence of published Canadian research that has explored these relationships. I investigated the relationship between health behaviours and health by income adequacy with a secondary analysis of data from the first cycle of the National Population Health Survey (NPHS), conducted by Statistics Canada in 1994-95. The sample consisted of 11.941 NPHS respondents 20-64 years of age who did not have an illness or disability that prevented them from being employed. As a whole, findings from a series of hierarchical multiple regression analyses did not provide adequate evidence to conclude that the effects of physical activity and smoking on self-perceived health status and chronic health conditions are conditional on income adequacy. Instead, findings showed that the health behaviours each had a similar degree of influence on the self-perceived health status and number of chronic health conditions of respondents at all income adequacy levels. Moreover, the magnitude of the relationships between the health behaviours and health measures was very small. By enhancing knowledge about both the nature and magnitude of the relationships among Canadians' income adequacy, health behaviours, and health, this study makes a significant contribution to the small body of research that has explored the possibility that the relationship between health behaviours and health varies by socioeconomic circumstances. I conclude the paper with a discussion of the implications that the findings have for public health policies and programs.

Adult↗

Children's behaviour and the urban environment: an ecological analysis.

This research examines the spatial distribution and ecological correlates of problem behaviour amongst children living in the most highly urbanised portion of Greater Victoria, British Columbia, Canada. Rates of problem behaviour within the sample differ substantially, at the census tract level, with respect to the mean rate calculated for the study area as a whole. While the degree of spatial concentration varies between behaviour types, each exhibits a similar overall trend, with the highest rates in the western and/or central portions of the study area, and the lowest rates around its northern and eastern periphery. Bivariate correlation analyses reveal significant ecological relationships between rates of problem behaviour and census measures of aggregate socio-economic status. The degree to which the urban ecology of the study area is related to census tract rates of problem behaviour is dependent upon the nature of the behaviour being considered. Results of contextual analyses using five ecological variables and their family-level equivalents suggest that, in some cases, census tract characteristics may have an independent impact upon behavioural status.

British Columbia↗

Gradients in risk for youth injury associated with multiple-risk behaviours: a study of 11,329 Canadian adolescents.

This study used the Canadian version of the World Health Organization-Health Behaviour in School-Aged Children (WHO-HBSC) Survey to examine the role of multiple risk behaviours and other social factors in the etiology of medically attended youth injury. 11,329 Canadians aged 11-15 years completed the 1997-1998 WHO-HBSC, of which 4152 (36.7%) reported at least one medically attended injury. Multiple logistic regression analyses failed to identify an expected association between lower socio-economic status and risk for injury. Strong gradients in risk for injury were observed according to the numbers of multiple risk behaviours reported. Youth reporting the largest number (7) of risk behaviours experienced injury rates that were 4.11 times (95% CI: 3.04-5.55) higher than those reporting no high risk behaviours (adjusted odds ratios for 0-7 reported behaviours: 1.00, 1.13, 1.49, 1.79, 2.28, 2.54, 2.62, 4.11; p(trend) < 0.001). Similar gradients in risk were observed within subgroups of young people defined by grade, sex, and socio-economic level, and within restricted analyses of various injury types (recreational, sports, home, school injuries). The gradients were especially pronounced for severe injury types and among those reporting multiple injuries. The analyses suggest that multiple risk behaviours may play an important role in the social etiology of youth injury, but these same analyses provide little evidence for a socio-economic risk gradient. The findings in turn have implications for preventive interventions.

Adolescent↗

Inter and intra individual variations in physicians' verbal behaviour during primary care consultations.

It is well established that most medical interviews in primary care are characterised by a scarcity of patient-centred interventions and a predominance of doctor-centred behaviours. Less information is available on the intra- and inter-individual variability between the physicians' use of these categories. The study aimed to examine the impact of physician, physician's attribution of emotional distress, patients' GHQ-12 status and gender on the frequency of doctor and patient-centred verbal behaviours. A matched pair design involved six General Practitioners (GPs) and 238 patients. GPs'speech was classified using nine main categories derived from the Verona medical interview classification system (VR-MICS/D). Frequencies of the behaviours were calculated as percentages of total utterances per interview. Parametric and non-parametric ANOVAs were performed with GHQ-12 score, GP attribution of psychological distress, gender, and the six GPs as main factors. GPs varied in their use of the various interviewing behaviours. GHQ-12 status had no impact on GPs' interview behaviour, while GPs' distress attribution was associated with an increase of closed psychosocial questions and a decrease of closed medical questions. Within comparisons showed that each GP tended to change very little and only as a function of attribution: four out of six GPs increased closed psychosocial questions with patients they thought to be distressed. Patients' gender did not significantly alter GPs' interviewing behaviour. The variability in the use of specific verbal behaviours among GPs indicates a highly individualised approach and the lack of a common interview strategy. The fact that GPs' interviewing styles did not change according to patient characteristics, such as emotional distress, but only according to attribution further indicates that GPs untrained in communication techniques tend to use a predominant doctor-centred approach to the medical interview.

Adult↗

Unsafe sexual behaviour in South African youth.

A growing body of evidence points to the complexity of sexual behaviour. HIV risk behaviour is influenced by factors at three levels: within the person, within the proximal context (interpersonal relationships and physical and organisational environment) and within the distal context (culture and structural factors). This paper presents the findings of a review of research on the factors promoting and perpetuating unsafe sexual behaviour in South African youth. Papers included in the review were dated between 1990 and 2000 and addressed sexual behaviour of youth between the ages of 14 and 35 years. Both published works and unpublished reports and dissertations/theses were included. The review concluded that at least 50% of young people are sexually active by the age of 16 years; the majority of school students who had ever experienced sexual intercourse reported at the most one partner in the previous year, with a persistent minority of between 1% and 5% of females and 10-25% of males having more than four partners per year; and between 50% and 60% of sexually active youth report never using condoms. In terms of explanations for unsafe sexual behaviour among South African youth, the findings illustrate the powerful impact of the proximal and distal contexts, and in particular, the pervasive effect of poverty and social norms that perpetuate women's subordination within sexual relationships. Personal factors and the proximal and distal contexts interact to encourage HIV risk behaviour in ways that are not fully captured by social-cognitive models. The findings will be of interest to researchers and practitioners in the fields of adolescent sexual behaviour and HIV prevention in developing countries.

Adolescent↗

Can the school make a difference? A multilevel analysis of adolescent risk and health behaviour.

The main aim of this article is to assess the relationship between the structural and (health) policy variables of the school and characteristics of the individual on the risk and health behaviour of adolescents. Individual and school level effects on seven health-related behaviours are simultaneously estimated, using multilevel modelling. The data are from the Flemish health behaviour in school-aged children study in Belgium. Data are used from 29 Flemish schools in which students (N=3225), school administrators (N=29) and teachers (N=1132) were surveyed with anonymous written questions. The analysis confirms previous findings concerning individual level effects. Although differences between schools in risk and health behaviour were found to originate mainly from differences in pupil characteristics, substantial variation between schools remained with regard to regular smoking, drinking habits and tooth brushing after controlling for individual effects. A wide range of school structure and policy variables were taken into account, but only few of them were found to influence the health and risk behaviour of young people. Moreover, the study could not detect an effect of health promotion policy at school. The analysis therefore only partially confirms the hypothesis that the school has an impact on the health behaviour of young people. The findings demonstrate the need for a more thorough examination of the paths by which schools can influence the health behaviour of their pupils.

Adolescent↗