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Transport of tools and mental representation: is capuchin monkey tool behaviour a useful model of Plio-Pleistocene hominid technology?

Capuchin monkeys display greatly developed tool-using capacities, performing successfully a variety of tool-tasks. Impressed by their achievements in this respect, some investigators have suggested that capuchin tool-using behaviour could be used as a model of the tool behaviour of the first hominids. The transport of tools, a task requiring complex cognitive capabilities, is an essential ingredient in the technological behaviour of the first hominids. In this way, to qualify as another source for modelling hominid behavioural evolution, capuchins had to exhibit proficiency in the transport of tools. We investigated this problem through experiments designed to elicit the transport of objects. The results showed that the monkeys were able to transport food to be processed with the use of tools, but failed when the tools themselves had to be transported. Our hypothesis is that a limited capacity for abstract representation, together with the lack of a regulatory system ensuring that the food would not be lost and consumed by another individual during the search for and transport of the tools, were responsible for such a failure. We conclude that the tool-using behaviour of capuchins presents no functional analogy with the tool behaviour of the Plio-Pleistocene hominids, and that capuchin monkeys are a very inadequate source for modelling Plio-Pleistocene hominid's technological behaviour.

Animals↗

A comparison of behavioural effects and morphological features of grafts rich in cholinergic neurons placed in two sites of the denervated rat hippocampus.

This study compared the morphological characteristics and the behavioural effects of intrahippocampal septal cell suspension grafts injected either just above the pyramidal cell layer of the hippocampal region CA1 or within the dorsal leaf of the dentate gyrus (DG) in rats subjected to electrolytic fimbria-fornix lesions. The behavioural tests determined home-cage and open-field activity, as well as radial-maze performance. Cresyl-violet staining, acetylcholinesterase (AChE) histochemistry, and parvalbumin, glial fibrillary acidic protein and glutamic acid decarboxylase immunocytochemistry were used for morphological assessments. The cross-sectional area of the grafts was measured between 0.8 mm and 5.3 mm posterior to Bregma and used as an index of their development. Whether injected into CA1 or DG, the grafts provided the partially denervated hippocampus with a dense AChE-positive reinnervation. Both types of grafts were devoid of reactive astrocytes (although reactive astrocytes were found close to the graft-host interface), contained almost no parvalbumin-positive neurons and showed a high density of GAD-positive terminals. One of the main differences between the two groups of grafted rats was that the suspension injected into the DG yielded grafts that, in the vicinity of the injection sites (between 2.3 mm and 4.3 mm posterior to Bregma), had a cross-sectional area exceeding that of the grafts placed into CA1 by about 63-110% (average 79%), the latter being more dispersed than the former in the coronal plane. In addition, rats with grafts in the DG exhibited granule cell degeneration in the vicinity of the injection sites, whereas rats with grafts in region CA1 showed no damage near the injection sites. Concerning the behavioural data, we found that fimbria-fornix lesions induced hyperactivity in both the home cage and the open field and impaired radial-maze performance. Compared with the lesion-only rats, the grafted rats in both groups had further increased open-field and home-cage activity. While the grafts placed into region CA1 slightly, but significantly, accentuated the lesion-induced deficit in radial-maze performance, those placed into the DG had no effect. These results suggest that intrahippocampal grafts may, in some (still unspecified) conditions, produce adverse behavioural effects or no behavioural effects, despite an acceptable graft-induced cholinergic reinnervation of the hippocampus. They do not allow a clear answer to the question of whether intra-DG and intra-CA1 septal suspension grafts exhibiting almost comparable morphological features (except in their size and their dispersion in the vicinity of the injection sites) induce behavioural effects that would depend on intrahippocampal location of the grafts. They suggest, however, that the granule cell degeneration caused by the implantation procedure, in conjunction with the intragyral development of the graft, probably does not account for some of the reported adverse behavioural effects of intrahippocampal basal forebrain grafts. Finally, the finding that septal cell suspensions placed into the DG yielded larger grafts than when an equivalent number of cells was injected into CA1 might be explained by a larger lesion-induced neurotrophic activity in DG than in region CA1, although both regions had undergone a similar degree of cholinergic denervation.

Acetylcholinesterase↗

Effects of ethyl alcohol on behaviour in nursing female mice.

Effects of administering 10% ethyl alcohol as drinking fluid to mice during pregnancy and lactation have been examined by ethological analysis of behaviour of nursing females in their home cages at 1 day, 5--7 days, and 12--14 days postpartum. The treatment with alcohol did not affect gestation period or litter size, and fluid intake of treated mice remained similar to that of controls, the average intake of alcohol amounting to 29 mg/g body weight during lactation. Increase in frequency of exploration at 1 day postpartum was the only significant behavioural effect of alcohol on the nursing female mice. Duration of Non-Social Behaviour was unaltered, and no effects of the treatment on Maternal Behaviour or on Social and Sexual Investigation of male partners could be demonstrated. Behaviour of nursing females changed with increase in age of their pups. This occurred to a similar extent in treated and control animals. Maternal and Non-Social Behaviours declined in frequency as the pups became older although the time spent in these behaviours remained fairly constant. Social Investigation of the male partner declined both in frequency and duration while females were nursing their pups.

Animals↗

Measurement of acute and chronic behavioural effects of methamphetamine in the mouse.

A simple and reliable method was developed for rating the dose-related behavioural effects of methamphetamine in male Swiss Albino mice for acute or chronic drug treatment. This procedure was based on a frequency count of certain behaviours made at 15-min intervals over a 90-min period following drug administration. The Fisher Randomization procedure was adapted to analyze behavioural data for the chronic studies. Clear-cut, dose-related behavioural responses occurred following acute (+)-methamphetamine administration and ranged from decreased quiescence (0.64 mg/kg) through increased locomotor activity (2.5 mg/kg), a mixture of stereotyped behaviour and increased locomotor activity (5.0 and 7.5 mg/kg), to primarily stereotyped gnawing, licking or sniffing (10 mg/kg). In studies involving chronic administration of (+)-methamphetamine at 0.64, 2.5 and 10 mg/kg conducted over six and seven weeks, behavioural responses were more exaggerated than in acute studies. All behaviours returned to normal levels in the recovery week except for locomotor activity at the 10 mg/kg dosage. In some animals, chronic treatment with 10 mg/kg (+)-methamphetamine led to protracted self-tearing that replaced the gnawing, licking, sniffing stereotype.

Animals↗

Behavioural problems of children with chronic physical illness and their siblings.

Children suffering from chronic physical illness are considered to be at increased risk for behavioural problems. There is also evidence that their siblings are at risk for behavioural problems. This study investigated parent-reported behavioural problems in chronically ill children and their siblings. There were significant positive correlations between the behaviour problem scores of the ill children and the scores of their siblings. Siblings older than the ill child had significantly higher behaviour problems scores of an internalizing nature than did the younger siblings. Sibling behaviour problem scores were similar to those of a comparison group of normal children and significantly different from those of a comparison group of psychiatrically referred children. Siblings of chronically ill children showed no greater likelihood of receiving scores in the clinical range of behaviour problems than children in the general population. Implications of the findings and suggestions for future research are discussed.

Adolescent↗

The effects of maternal depression on child conduct disorder and attention deficit behaviours.

The relationships between maternal history of depressive symptoms during children's middle childhood (8-11 years) and/or concurrent maternal depressive symptoms on the one hand and teacher and self reports of conduct disorder and attention deficit behaviours when the children were 12 and 13 years old on the other were studied in a birth cohort of New Zealand children. Examination of the joint effects of maternal history of depression and concurrent depressive symptoms on child behavior showed consistent and statistically significant associations between maternal history of depression and behaviour reports. However, associations between maternal concurrent depressive symptoms and child behaviour were generally non-significant when the effects of maternal history of depression were controlled. These results persisted when errors of measurement in behaviour reports were taken into account. However, after adjustment for potentially confounding social and contextual factors the correlations between maternal history of depression and child behaviour reduced to the point of both practical and statistical non-significance. We concluded that, for this cohort, the association between maternal depressive symptoms and externalising behaviour in early adolescence arose largely from the effects of common contextual factors (principally social disadvantage and marital instability) that influenced both rates of maternal symptomatology and rates of childhood problem behaviours.

Adolescent↗

Similar behavioural effects of sigma agonists and PCP-like non-competitive NMDA antagonists in guinea-pigs.

The present study examined the behavioural effects of sigma agonists and PCP-like non-competitive N-methyl-D-aspartate (NMDA) antagonists in guinea-pigs. Subcutaneous (SC) injection of the putative sigma agonist (+)NANM (1 and 10 mg/kg SC) and (-)NANM (1 and 10 mg/kg SC) produced a behavioural response in guinea-pigs which was characterized by sedation and exophthalmos, with locomotor depression, flattened posture and flaccidity, whereas the sigma ligand pentazocine induced sedation but no flattened posture. Ketamine (20 mg/kg SC) and (+)dizocilpine (0.025, 0.1 and 1 mg/kg SC) produced similar effects to those of (+) and (-)NANM. However, the putative sigma receptor ligand DTG (1 and 10 mg/kg SC) had no observable effect on behaviours in guinea-pigs, similar to results for other species. The behavioural effects produced by (+) and (-)NANM were not reversed by injection 1 h later of naloxone hydrochloride (15 mg/kg SC), haloperidol (10 mg/kg SC) or DTG (10 and 30 mg/kg SC), but the effects of all drugs were reversed by the selective dopamine D-2 agonist quinpirole (3 mg/kg IP). Moreover, injection of naloxone (15 mg/kg SC), DTG (10 and 30 mg/kg SC) or haloperidol (1 and 10 mg/kg SC) 10 min before, did not reverse the behaviour induced by (+)NANM (10 mg/kg SC). These data indicate that sigma and PCP-like drugs have a similar gross behavioural effect in guinea-pigs, possibly mediated by non-competitive antagonism of the NMDA subtype of glutamate receptors. The results demonstrating behavioural depression were in contrast to the stimulatory effects of these drugs at similar doses in other rodent species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

D-cycloserine enhances social behaviour in individually-housed mice in the resident-intruder test.

D-Cycloserine (DCS) has been reported to affect the central nervous system in man. To investigate whether the compound produces specific behavioural effects, DCS was administered to male mice in a resident-intruder situation and the behaviour of the interacting mice assessed using ethological analysis. Resident mice given DCS (32.0-320.0 mg/kg PO, 60 min before testing) showed dose-dependent increases in social investigation, smaller increases in sexual behaviour and decreased aggressiveness. Defensive and flight behaviour were not affected. Intruder mice showed slight increases in sexual behaviour that were not dose-dependent, and small increases in social investigation. The increases in social investigation induced by DCS (320.0 mg/kg) in resident mice were not reversible with R-HA 966 (32.0 mg/kg IP, 30 min before testing), a blocker of the strychnine-insensitive glycine modulatory site associated with the N-methyl-D-aspartate receptor, but were blocked by the GABA antagonist bicuculline (0.56 mg/kg IP, 5 min before testing). The small DCS-induced increase in sexual behaviour in residents was reversed by R-HA 966. Within the parameters of the resident-intruder situation, DCS exerts socio-sexual behaviour-enhancing effects which are dependent upon the role of the interactant, and which are mediated by an action upon multiple substrates. DCS may be regarded as another example of a sociotropic (approach-promoting) agent.

Aggression↗

Clozapine acts as a 5-HT2 antagonist by attenuating DOI-induced inhibition of male rat sexual behaviour.

Evidence has been reported that clozapine may derive part of its therapeutic effects in treatment-resistant schizophrenic patients by interacting with the serotonin system. Among the few behavioural models available to test the hypothesis of an interaction of clozapine with 5-HT2 receptors, male rat sexual behaviour is particularly useful, since in this behaviour 5-HT1A and 5-HT2 receptors have opposite functions. Stimulation of 5-HT1A receptors facilitates ejaculatory behaviour and stimulation of 5-HT2 receptors inhibit ejaculation. In the present study, male rat sexual behaviour was depressed by treatment with DOI (1.0 mg/kg), a selective 5-HT2 receptor agonist. The depressive effect of DOI was attenuated by the administration of clozapine (0.1-1.0 mg/kg) in doses that by themselves did not significantly affect sexual behaviour. It was concluded that clozapine in the male rat sexual behaviour model may be interpreted as serving as a 5-HT2 antagonist.

Animals↗

Evaluation of BR-16 A (Mentat) in cognitive and behavioural dysfunction of mentally retarded children--a placebo-controlled study.

It is important to control abnormal behaviour and hyperactivity, and improve cognition in mentally retarded children (MRC), which would help in their education, training and subsequent rehabilitation. Recently it has become known that amongst other side-effects, protracted use of anti-convulsant medication induces cognitive and behavioural dysfunction, which is a major problem in mentally retarded epileptics. In a placebo-controlled study, we confirmed the efficacy of a herbal preparation, BR-16A (Mentat) in controlling such behavioural and cognitive deficits in 40 mentally retarded children. The efficacy of this remedy was further evaluated in 19 MRCs with epilepsy. Twelve patients had generalised seizure, 4 with partial and 3 with mixed seizure pattern was continued. Inspite of the usual antiepileptic treatment, the frequency of seizures ranged from 1 to 7 attacks in periods from 1 week to 1 year. With active drug Br-16A, it was possible to note a reduction in seizure frequency. Patients with higher frequency responded better. There was no further increase in the dosage of antiepileptic drugs. There was significant control of other abnormal behaviour as shown by reduction in rating score on the Children's Behavioural Inventory test. BR-16A was effective in controlling abnormal behaviour, especially hyperactivity and incongruous behaviour in mentally retarded children with and without epilepsy.

Adolescent↗

Prevalence of abnormal eating behaviours and inappropriate methods of weight control in young women from Brazil: a population-based study.

OBJECTIVE: The aim of this epidemiological investigation was to study the prevalence of abnormal eating behaviours in a community sample of young women from Porto Alegre, RS, Brazil. METHODS: The research team visited 1524 randomly selected households in Porto Alegre and invited all of the women aged 12-29 years to participate in the study: 513 women subsequently completed a socio-economic and demographic questionnaire, the Bulimic Investigatory Test (BITE) and the Eating Attitudes Test (EAT-26). RESULTS: Clinically significant disturbed eating behaviour was revealed in the 16.5% of women who had EAT scores above the cut-off point of 21; 2.9% also had BITE symptom scores of > or = 20. The participants were categorised into three groups on the basis of a new variable combining both instruments: those with abnormal eating behaviours (10.9%), those with unusual eating patterns (23.8%), and those with normal eating behaviours (60.2%). Abnormal eating behaviours were significantly more prevalent in the 16-19 year age range (p = 0.007) and were also more prevalent among overweight/obese women (p = 0.009). Laxative use was reported by 8.5% of the women, followed by fasting (3.1%), use of diuretics (2.8%) and vomiting (1.4%). CONCLUSIONS: Abnormal eating behaviours are fairly common among young women in Brazil. In comparison with other population studies, this survey showed a similar use of laxatives, less self-induced vomiting and a greater use of diet pills (probably because they are less strictly controlled in Brazil). Educational programmes aimed at preventing abnormal eating behaviours and developing healthy weight control practices among children and young adolescents should become public health priorities.

Adolescent↗

Relationship of orofacial movements to behavioural repertoire as assessed topographically over the course of 6-month haloperidol treatment followed by 4-month withdrawal.

RATIONALE: Late-onset vacuous chewing movements (VCMs) arise in a significant proportion of rats treated chronically with conventional antipsychotic drugs. Given their common action to block dopamine D2-like receptors, VCMs may be related to changes in dopaminergic function; if so, other typical dopamine-mediated behaviours might be altered also. OBJECTIVE: To examine this hypothesis, behavioural repertoire was studied topographically over the course of chronic treatment and withdrawal. METHODS: Animals were injected with haloperidol decanoate 28 mg/kg IM, or vehicle, every 3 weeks for 27 weeks, and then maintained without treatment for a further 18 weeks. Immediately before each injection and during withdrawal, VCMs and other topographies of behaviour were assessed. RESULTS: In both control and haloperidol-treated rats, exploratory behaviours declined over the study, indicating habituation effects. Conversely, VCMs emerged after 6 weeks of treatment with haloperidol and persisted after withdrawal; VCM and locomotion were not related, indicating that in treated rats, increased VCMs are not an artifact of reduced locomotion. Treated animals with VCMs evidenced increases in buccal tremor and grooming behaviour relative to those without VCMs, although no clear relationship to the emergence of VCMs was established; there were no material differences in any other topographies of behaviour. CONCLUSION: The effect of long-term treatment with haloperidol to induce VCMs is not reflected in fundamental changes in dopamine-mediated behavioural topography but, rather, appears to affect neural mechanisms involved in orofacial movement preferentially.

Animals↗

Measuring impulsivity in mice using a novel operant delayed reinforcement task: effects of behavioural manipulations and d-amphetamine.

RATIONALE: The increasing use of genetically modified mice to probe genetic contributions to normal and abnormal behaviours requires the development of sensitive and selective behavioural tasks. OBJECTIVES: To develop a discrete trial assay of impulsivity (delayed reinforcement) that is tractable in mice utilising a mouse operant nine-hole box apparatus and to specify the task with respect to behavioural and pharmacological manipulations. METHODS: Mice were trained to respond with a nose-poke to one of two visual stimuli; one response resulted in a small quantity of reinforcer, the other in a larger quantity of reinforcer. As the session proceeded increasing delay was introduced onto the response leading to the large reward. Hence, the nature of the choice was a small quantity of reinforcer immediately versus a larger but progressively delayed amount of reinforcer. At stable baseline performance the mice were challenged with a variety of task manipulations and systemic d-amphetamine in order to discern aspects of the underlying psychological and neurochemical substrates of the choice behaviour. RESULTS: The mice showed a systematic shift in responding away from the large reinforcer with increasing delay (0, 2, 4, 8, 12 s), such that at the longest delay >80% of nose-pokes were for the smaller, immediate reinforcer. Task manipulations indicated that behaviour was controlled in a trial discrete manner by the contingency between delay and reward and was not due to non-specific factors such as satiation. d-Amphetamine had complex, dose dependent effects on choice behaviour which revealed dissociations between impulsive choice and hyperactivity. CONCLUSIONS: We have successfully developed an assay of impulsivity in mice that will be of utility to examine impulsive behaviours and their genetic substrates. In addition, our data provided evidence of distinct dopaminergic mechanisms mediating aspects of impulsivity and hyperactivity.

Amphetamine↗

The psychopharmacology of impulsive behaviour in rats VIII: effects of amphetamine, methylphenidate, and other drugs on responding maintained by a fixed consecutive number avoidance schedule.

RATIONALE: Impulsive behaviour is a component of psychiatric disorders such as bipolar disorder, attention deficit hyperactivity disorder (ADHD), or personality disorders. Most experimental studies on impulsive behaviour punish impulsive choices by loss or delay of reward. In the present study, impulsive behaviour was punished by an explicitly aversive stimulus, using a novel fixed consecutive number (FCN) schedule of electric shock avoidance. OBJECTIVES: This study was conducted to demonstrate stable performance using the FCN avoidance procedure, and examine the effects of drugs previously shown to affect impulsive behaviour using a conventional FCN schedule. METHODS: First, rats were trained in the appetitive FCN procedure. Pressing the right lever in an operant conditioning chamber after having pressed the left lever at least six times delivered a food pellet (FCN6). Responses on the right lever before completing this ratio resulted in a time out and restarted the ratio. The rats were then switched to FCN avoidance. Responses on the right lever made before completion of the ratio also resulted in food delivery, but were accompanied by an electric shock. RESULTS: Chlordiazepoxide (10.0 mg/kg), ethanol (1.0 g/kg), and haloperidol (0.1 mg/kg) increased impulsive behaviour by reducing the number of left lever responses made before the right lever was pressed. Imipramine (1.0-10.0 mg/kg) and desipramine (1.0-10.0 mg/kg) had no effect on impulsive choice. Amphetamine (0.4 and 0.8 mg/kg) and methylphenidate (6.0 mg/kg) significantly increased the mean chain length, and the proportion of very long chains, indicative of reduced impulsivity, although this did not improve efficiency. CONCLUSIONS: The increases in impulsivity produced by chlordiazepoxide, ethanol, and haloperidol were similar to those under appetitive FCN schedules. In contrast, amphetamine and methylphenidate, by reducing impulsivity in the FCN avoidance, induced effects opposite to those observed in an appetitive FCN procedure. These results suggest that the therapeutic actions of stimulants, to reduce impulsive behaviour in ADHD, may arise in part by increasing the control of behaviour by aversive stimuli.

Animals↗

The effects of excitotoxic lesions of the basolateral amygdala on the acquisition of heroin-seeking behaviour in rats.

RATIONALE: Second-order schedules of drug-self-administration provide a method of examining drug-seeking behaviour, which is maintained in part by the presentation of a discrete, drug-associated light CS. Previous results have found that lesions of the basolateral amygdala (BLA) impair the acquisition of i.v. cocaine self-administration under this type of schedule. OBJECTIVES: The present experiments examined the effects of excitotoxic lesions of the BLA on the acquisition of i.v. heroin self-administration under both continuous reinforcement and second-order schedules, in order to investigate possible commonalties in the neural basis of heroin- and cocaine-seeking behaviour. METHODS: Rats received quinolinic acid or sham vehicle lesions of the BLA prior to i.v. self-administration training. Initially, heroin self-administration under a continuous reinforcement schedule was acquired. Each active lever-press resulted in a 0.04 mg i.v. heroin infusion, paired with presentation of a 20-s light conditioned stimulus. Following acquisition of responding under this schedule, the response requirement was gradually increased to a second-order schedule of FI15(FR5:S). RESULTS: There was no effect of lesions of the BLA on the acquisition of heroin self-administration under a continuous reinforcement schedule. The acquisition of heroin-seeking behaviour under a second-order schedule of self-administration was not affected by lesions of the BLA, but lesioned rats showed a significantly higher baseline level of responding. CONCLUSIONS: These results indicate that the rewarding effects of heroin do not depend on the integrity of the BLA. The BLA is also not critically involved in mediating heroin-seeking behaviour under a second-order schedule of reinforcement, and this stands in marked contrast to the effects of BLA lesions on the acquisition of cocaine-seeking behaviour. These findings suggest that discrete heroin cues were not critical in maintaining heroin-seeking behaviour under the second-order schedule used here and that other learning systems are engaged in the control of this behaviour.

Amygdala↗

Differences in anxiety-related behaviours and in sensitivity to diazepam in inbred and outbred strains of mice.

RATIONALE: Natural strain differences exist in mice for behavioural traits such as emotional reactivity. OBJECTIVE: The present experiments compared the behavioural profiles of nine strains of mice (BALB/c, C57BL/6, C3H, CBA, DBA/2, NMRI, NZB, SJL, Swiss) in two models of anxiety after the administration of the benzodiazepine diazepam. METHODS: The tests used were the light/dark choice task and the elevated plus-maze, two well-validated anxiolytic screening tests. RESULTS: In vehicle-treated animals, differences on variables designed to measure anxiety-related behaviours were observed in both tests. In the light/dark test, the strains could be divided into three distinct groups: two non-reactive strains (NZB and SJL), an intermediate-reactive group (C3H, CBA, DBA/2, NMRI, C57BL/6 and Swiss), and one highly reactive strain (BALB/c). In the elevated plus-maze, SJL, NMRI, CBA and, to a lesser extent, C3H strains of mice, consistently showed low levels of anxiety-related behaviours. Intermediate levels were seen in the Swiss and BALB/c strains, and high levels of emotional reactivity were seen in C57BL/6, DBA/2 and NZB. The strain distribution between the light/dark and the elevated plus-maze tests shows similarities and differences, suggesting that each of these experimental procedures represents a different set of behaviours. Marked differences between a number of strains of mice in their sensitivity to the anxiolytic-like action of diazepam were observed in both the light/dark and the elevated plus-maze tests. Mice of the BALB/c, Swiss and, to a lesser extent, CBA and C3H strains were responsive to diazepam in both tests, although in the case of CBA mice, effects may have been contaminated by behavioural suppression. SJL mice were largely unresponsive to the action of the benzodiazepine in both tests, whereas in C57, DBA/2, NMRI and NZB mice, diazepam produced positive effects only in the elevated plus-maze. CONCLUSION: The finding of differential strain distributions both with and without diazepam treatment in the light/dark and the elevated plus-maze tests, indicates that not all strains of mice are suitable for investigating the effects of GABA/BZ receptor ligands. This study may thus provide a useful guide for choosing the best strain of mice for studying the pharmacology of fear-related behaviours.

Animals↗

Pharmacological manipulation of ultrasound induced defence behaviour in the rat.

Rats exposed to aversive stimuli display species specific defence behaviour as part of their natural survival strategy. one component of this behaviour is the production of ultrasonic calls in the 20 to 27-kHz range, which are thought to serve a communicative role. The present study has examined the behavioural effects of exposing rats to artificially generated ultrasound and the ability of three distinct pharmacological agents to modify this response. Single tone 20 kHz ultrasound exposure for 1 min produced intensity-related locomotor behaviour, characteristic of defence behaviour, which could be measured using a computer tracking system. This was significantly reduced by peripheral pretreatment with the benzodiazepine, diazepam (0.3 and 3.0 mg/kg IP). Pretreatment with the 5-HT agonist 1-(3-chlorophenyl) piperazine (mCPP) (0.5-2.0 mg/kg IP) produced a dose-related reduction in the ultrasound-induced response. The alpha 2 adrenoceptor antagonist, yohimbine (0.5-5.0 mg/kg IP), caused an increase in the response at the lower dose (0.5 mg/kg) and a decrease at the two higher doses (2.0 and 5.0 mg/kg). The present findings suggest that defence behaviour in the rat can be artificially produced by 20 kHz ultrasound; this is sensitive to pharmacological manipulation and may offer a novel animal model of aversive behaviours that are associated with human panic.

Adrenergic alpha-Antagonists↗

Enhancement of dopamine-mediated behaviour by the NMDA antagonists MK-801 and CPP: similarities with repeated electroconvulsive shock.

The behavioural effect of dopamine D1-like receptor agonists (SKF 38393, SKF 81297) and a D2-like receptor agonist (quinpirole), administered alone and in combination, was tested in rats pretreated with a single injection of an NMDA antagonist (MK-801, CPP) or vehicle. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Pretreatment with MK-801 (0.05 mg/kg, SC, 30 min) had no significant effect (compared to controls) on the behavioural response to SKF 38393 (7.5 mg/kg SC), SKF 81297 (0.2 mg/kg SC) or quinpirole (0.1 and 0.25 mg/kg SC) administered alone. In contrast, MK-801 markedly increased locomotion (activity counts and scores) induced by co-administration of a D1-like plus a D2-like agonist [SKF 38393 (7.5 mg/kg) plus quinpirole (0.25 mg/kg), SKF 81297 (0.2 mg/kg) plus quinpirole (0.1 mg/kg)]. The behavioural response to the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) was also enhanced by MK-801. Pretreatment with CPP (0.1 mg/kg SC, 30 min) also significantly increased the locomotor response to co-administration of SKF 38393 plus quinpirole administered alone, but had no effect on the behavioural response to separate injection of these agonists. MK-801 (0.05 mg/kg SC, 30 min) also enhanced the behavioural response to bilateral injection into the nucleus accumbens of SKF 38393 plus quinpirole (1.0 plus 0.4 microgram/side, respectively). These data suggest that in the intact rat, the enhancement of dopamine-mediated behaviour by either MK-801 or CPP requires concomitant stimulation of D1-like and D2-like receptors, possible located within the nucleus accumbens. The effect of these NMDA antagonists on dopamine function is similar to that of repeated electroconvulsive shock (ECS), indicating that one of the actions of ECS may be to reduce NMDA receptor function.

Animals↗