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Differentiating the behavioural profile in autism and mental retardation and testing of a screener.

In order to differentiate the behavioural profiles in autism and mental retardation and to cross-validate a behavioural autism screen, 84 subjects with autism (64 males and 20 females) with a mean age of 10 years selected from a Swiss national survey were compared to a control group of 84 subjects matched by age and gender with mental retardation, but without autistic features. The behavioural profile was assessed using the Developmental Behaviour Checklist (DBC). The behavioural profile in autism, in contrast to mental retardation, was marked by higher scores in the domains of disruptive, self-absorbed, communication disturbed, anxious and autistic behaviour, and a higher total DBC score. Furthermore, a higher vulnerability for behavioural abnormalities became evident for females with autism. A recently proposed DBC-Autism Screen was cross-validated, and a slight extension of the screen led to even higher correct classification rates. It was concluded that the DBC is a suitable instrument for the assessment of the behavioural profile and for screening in autism.

Autistic Disorder↗

Attention and behavioural problems of Finnish adolescents may be related to the family environment.

BACKGROUND: Adolescents' attention and behavioural problems in relation to the family environment were studied in the Northern Finland 1986 Birth Cohort. METHOD: Fifteen-year-old adolescents (N=6888) completed the Youth Self-Report (YSR) questionnaire and their parents (N=6643) completed the Strengths and Weaknesses in ADHD and Normal Behaviours (SWAN) questionnaire. The ratings were compared in relation to gender and family characteristics. RESULTS: Girls scored higher than boys on the YSR attention problems subscale (means 4.61 vs. 3.41), the rule-breaking behaviour subscale (means 4.25 vs. 3.69) and the aggressive behaviour subscale (means 7.18 vs. 5.63). Parents reported more SWAN attention problems in their sons than in their daughters. Living in an other than intact family increased YSR and SWAN attention problems and YSR behavioural problems in both genders. Adolescents living in very large families (11-19 children) had least attention and behavioural problems. CONCLUSIONS: Attention and behavioural problems seem to be common among adolescents in Finland. For both genders, living in other than intact families increases especially behavioural problems. Additionally, a very large family seems to be a protective factor against those problems.

Adolescent↗

Associations between disturbed sleep and behavioural difficulties in 635 children aged six to eight years: a study based on parents' perceptions.

Associations between sleep and behaviour in 635 children, aged six to eight years, were investigated using parental responses to a sleep habits questionnaire, and to a behavioural screening form, the Strengths and Difficulties Questionnaire (SDQ). Global reports of sleep problems in 4.9% of the children were associated with a total SDQ score indicative of behaviour problems in 36% of the cases. Conversely, 15% of children with behaviour problems had global reports of sleep problems. Associations between specific sleeping features and different dimensions of behaviour and emotions were also explored. Hyperactivity was associated with tossing and turning during sleep, and with sleep walking; conduct problems were related to bedtime resistance; and emotional symptoms were associated with night terrors, difficulty falling asleep and daytime somnolence. Peer problems were associated with somewhat shorter total sleep time. Finally, a total SDQ score indicative of behaviour problems was associated with bedwetting, nightmares, tossing and turning during sleep and sleep walking, as well as with a slightly shorter total sleep time. We conclude that sleep and behaviour problems are associated in children, and that characteristic associations exist between particular sleep disturbances and specific dimensions of behaviour.

Affective Symptoms↗

Unusual behaviour of captive-raised gibbons: implications for welfare.

Unusual behaviours not normally seen in the wild were studied in 52 captive agile (Hylobates agilis albibarbis) and 23 Müllers gibbons (H. muelleri spp) at three locations within the Kalaweit Gibbon Rehabilitation Project. Unusual behaviours included stereotypic behaviour (SB), human-directed masturbation and posterior presenting. These data were collected over 18 months as part of an ongoing study into behavioural adaptation of gibbons in a rehabilitation programme. Data were also collected on the unusual behaviours observed, for example, SB, human-directed masturbation and posterior presenting. I suggest causes of the abnormal behaviours and propose solutions to reduce their incidence in order to improve the gibbon's progress in rehabilitation. From this study I conclude that most gibbons can be rehabilitated from the point of view of acquiring and maintaining a normal behavioural repertoire once in suitable housing. Encouraging the gibbons to reduce and/or stop these unusual behaviours is key to the welfare of the gibbons while in the rehabilitation programme and to successful release into a forest habitat.

Animal Welfare↗

Different functions of spinal 5-HT1A and 5-HT2 receptor subtypes in modulating behaviour induced by excitatory amino acid receptor agonists in mice.

The modulating effects of 5-HT1A and 5-HT2 receptor agonists on behaviour spinal excitatory amino acid (EAA) agonists were examined. Intrathecal (i.th.) administration of both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) produce a behavioural syndrome of caudally directed biting and scratching. Serotonin (5-HT) agonists were coadministered with either NMDA or AMPA, and changes in EAA-induced behaviour were scored. All drugs were administered i.th. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) (15-60 nmol) reduced both NMDA (0.25 nmol) and AMPA (0.06 nmol) induced behaviour in a dose-dependent manner, and preadministration of the 5-HT1A receptor antagonist, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide (NAN-190) (20 nmol) reversed this effect. The administration of the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.7-28 nmol) produced a dose-dependent behavioural syndrome similar to the EAA agonists. This was reversed by preadministration of ritanserin (10 nmol), a 5-HT2 antagonist. When DOI was coadministered with NMDA (0.25 nmol) or MAPA (0.06 nmol) there was an increase in the behaviour recorded and this effect was antagonised by ritanserin. The results of this study implicate that in the spinal cord subtypes of 5-HT receptors have different effects on modulation of behaviour induced by activation of the NMDA or the AMPA receptors; the activated 5-HT1A receptors have an inhibitory effect whereas activation of the 5-HT2 receptors enhance the induced behaviour.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Behavioural responses of bicucculline methiodide injections into the ventral hypothalamus of freely moving, socially interacting rats.

Several studies, using electrical stimulation of parts of the hypothalamus, have shown, that different parts of the hypothalamus yield different behavioural responses upon stimulation. In order to differentiate between stimulation of neuronal cell bodies and passing fibres and to investigate the role of GABA in hypothalamically elicited behaviour, 25 local injections with bicucculline methiodide, a GABA antagonist, (35 ng/0.2 microliter) were performed in the ventral parts of the hypothalamus of 16 freely moving rats in a social environment. A cannula system was used that allowed injection without interruption of the ongoing social interactions. Digging, gnawing, drinking and attack behaviour were elicited in different animals. By plotting the behavioural responses of the animals into a detailed hypothalamic atlas, we assessed the hypothalamic distribution of the elicited behavioural responses. A number of injections elicited a combination of two or three different responses, probably due to diffusion of the substance, thus disinhibiting more than one behavioural system. Our results are in general agreement with previous electrical stimulation data and show that, in an overlapping pattern, different populations of neurons are involved in the elicitation of digging, gnawing, drinking and attack behaviour. In the hypothalamus, a tonic GABAergic inhibition of neurons involved in the display of these types of behaviour appears to exist.

Aggression↗

Involvement of the nucleus accumbens in oral behaviour in the freely moving rat.

The role of the nucleus accumbens in oral behaviour was examined by intra-accumbens injections of a single dose of a selective dopamine D1 receptor agonist (SKF 38393: 5 micrograms/side), a selective dopamine D2 receptor agonist (quinpirole: 10 micrograms/side), and their combination in freely moving rats. Principal factor analysis revealed four factors to be involved in the scored behaviours, two of which concerned oral behaviour: a chew factor, comprising the behaviours chew, tongue protrusion, yawn and lick, and a groom factor, with high factor loadings of tremor and groom. The two remaining factors were the circle factor comprising circle, walk and rear, and the sniff factor comprising sniff, yawn and rear. Two-way ANOVA (independent variable D1 with H2O and SKF 38393 level; independent variable D2 with H2O and quinpirole level) of the factor scores revealed that SKF 38393 and quinpirole had similar or opposite effects which were additive or antagonistic, depending on which behaviour was studied. This study demonstrates that (a) the nucleus accumbens plays a major role in the oral behaviour of freely moving rats, and (b) an integrated study of all oral behavioural elements is necessary to describe the effects of drugs on oral behaviour.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Roles of dopamine and 5-hydroxytryptamine in stereotyped and non-stereotyped behaviour.

The roles of dopamine (DA) and 5-hydroxytryptamine (5-HT) in stereotyped and non-stereotyped components of the classical behavioural syndromes induced by 5-HT and DA were investigated by studying (a) behavioural interactions between the DA agonist apomorphine and the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and (b) the effects of depletion of 5-HT on the behavioural responses to amphetamine and p-chloroamphetamine. In agreement with evidence [Andrews, Fernando and Curzon (1982) Neuropharmacology 21:63-68] that non-stereotyped (i.e. body shakes and hind limb abduction) and stereotyped (i.e. head weaving and reciprocal forepaw treading) behaviour induced by d-amphetamine (25 mg/kg, i.p.) were inhibited and enhanced respectively by DA, apomorphine inhibited two non-stereotyped behavioural responses induced by 5-MeODMT (hind limb abduction and Straub tail) but enhanced reciprocal forepaw treading. However, head weaving was inhibited. Evidence indicated that behaviour induced by DA (whether stereotyped or not) was inhibited by 5-HT. Thus, the induction by apomorphine of sniffing and mouth movements was enhanced when the synthesis of 5-HT was inhibited. Also, p-chloroamphetamine caused sniffing and mouth movements only when 5-HT synthesis was inhibited. Under the latter conditions, while most classical behavioural responses associated with 5-HT did not occur, hind limb abduction persisted. Similarly, amphetamine (25 mg/kg) caused hind limb abduction and forepaw treading even when 5-HT was almost completely depleted. These results may indicate that the amine releasers have some direct 5-HT agonist properties. Results in general indicate the multiplicity of behavioural interactions between DA and 5-HT.

Animals↗

Behavioural and electrocortical changes induced by muscimol in rats withdrawn from chronic treatment with diazepam.

In rats withdrawn from a chronic treatment with diazepam, the effects of muscimol, given into the III cerebral ventricle, on behaviour and spectrum power of activity in the electrocorticogram (ECoG) were studied. In comparison to control rats which received only muscimol, in rats pretreated with diazepam (1 mg/kg/day for 30 consecutive days) the behavioural and ECoG effects of muscimol were significantly reduced or abolished. In fact, in rats pretreated with diazepam a small dose (50 ng) of muscimol did not affect behaviour or ECoG activity, in contrast to control animals in which the same dose produced, after a period of locomotor stimulation and ECoG desynchronization, typical and long-lasting behavioural sedation or sleep accompanied by a significant increase in total voltage power and in the lower frequency bands in the ECoG. In addition, larger doses (100 and 200 ng) of muscimol, which in control rats produced a typical biphasic pattern of ECoG and behavioural changes, i.e. an initial period of ECoG desynchronization and behavioural stimulation, followed by a second period of behavioural and ECoG sleep, in animals pretreated with diazepam, produced only an increase in total voltage power and in the lower frequency bands in the ECoG resembling the effects of the smaller (50 ng) dose. The present experiments suggest that, after chronic stimulation of benzodiazepine receptors a decrease in sensitivity of receptors for gamma-aminobutyric acid (GABA) occurs, since the effects of muscimol on behaviour and spectrum power were significantly reduced or abolished.

Animals↗

Systemic administration of dynorphin A(1-13) markedly inhibits different behavioural responses induced by cocaine in the mouse.

The effects of systemic administration (i.p.) of dynorphin A(1-13) on the cocaine-induced behavioural alterations in the mouse were determined by using multi-dimensional behavioural analyses, based upon a capacitance system. A 1.0 mg/kg dose of cocaine did not influence behaviour, while increasing doses to 3-30 mg/kg produced a significant increment in the frequency of behaviour, such as linear locomotion, circling, rearing and grooming. Although a 1.0 mg/kg dose of dynorphin A(1-13) alone produced a significant decrease in grooming behaviour, larger doses (3.0 and 10.0 mg/kg) of the peptide failed to affect different behaviour. The cocaine (3.0 mg/kg)-induced increases in linear locomotion, circling and rearing behaviour were significantly inhibited by dynorphin A(1-13) (10.0 mg/kg). The inhibitory effects of dynorphin A(1-13) (10.0 mg/kg) were antagonized by the opioid antagonist Mr 2266 (5.6 mg/kg). It is thus possible that the systemic administration of dynorphin A(1-13) inhibits different behavioural responses induced by cocaine through the blood-brain barrier, although the instability of amino acid bonds or the relatively large molecular weight of dynorphin A(1-13), may result in the failure to demonstrate opioid activity by the peptide after systemic administration.

Analgesics↗

Effect of cocaine on sexual behaviour in male stumptail macaques (Macaca arctoides).

The effect of cocaine (0.01-1.0 mg/kg) on sexual behaviour was studied in four male stumptail macaques (Macaca arctoides). Following drug-saline control administration, the behaviour of the male monkey with a female was observed for 30 min in two different behavioural conditions; in one of the conditions the baseline sexual activity was low, and in the other it was high (partial or complete separation of the male and the female between the sessions, respectively). The reversal of the cocaine-induced effects was attempted by haloperidol (0.003-0.01 mg/kg), a dopamine-2-receptor antagonist. Cocaine (0.1-1.0 mg/kg) produced a highly significant dose-dependent suppression in the number of ejaculations. The cocaine-induced suppression of ejaculatory behaviour was completely reversed by haloperidol. Haloperidol at the dose range used did not in itself influence ejaculatory behaviour. The effect of cocaine on grooming, nonejaculatory mounting, aggression, or perineal investigations did not reach statistical significance. The possibility that cocaine at very low doses (0.01-0.1 mg/kg) might increase sexual activity was excluded in the behavioural condition with a low basal sexual activity. The results indicate that cocaine dose-dependently suppresses ejaculatory behaviour as a result of dopamine-2-receptor-mediated mechanisms. The cocaine-induced suppression of ejaculatory behaviour might be explained by the strong rewarding effect of cocaine alone.

Animals↗

Modulation of plus-maze behaviour in mice by the preferential D3-receptor agonist 7-OH-DPAT.

Differences in the behavioural profiles of dopamine D2 receptor antagonists (e.g., haloperidol vs. sulpiride) in a animal models of anxiety have prompted speculation concerning the importance of their relative affinities for D2-like receptor populations. In an initial attempt to investigate the involvement of D3 receptors in anxiety, the present study examined the effects of the preferential D3-receptor agonist, (+/-)7-OH-DPAT (0.01-10.0 mg/kg), on behaviours displayed by male mice in the elevated plus-maze paradigm. An ethological approach incorporating measurement of a range of defensive acts and postures in addition to conventional parameters was used to provide a comprehensive behavioural profile for the compound. Data analysis indicated a significant increase in percentage of open-arm entries at 10 mg/kg and an altered temporal distribution of behaviour at 1-10 mg/kg. Furthermore, risk-assessment measures (stretched attend postures, closed-arm returns) were dose dependently reduced by drug treatment. Although these behavioural changes would be consistent with anxiety reduction, such an interpretation is negated by dose-dependent decreases in all active behaviours (arm entries, rearing, and head-dipping) and by marked increases in entry latencies and nonexploratory behaviour at the highest dose tested. Overall, these effects are remarkably similar to those previously reported for quinpirole, suggesting either that D2 and D3 receptors exert similar behavioural control or that the agents employed are sufficiently potent at D2 receptors to prevent a resolution of D2 and D3 responses.

Animals↗

Brain microdialysis and its application for the study of animal behaviour.

Microdialysis is a sampling method that is used to determine the extracellular concentration of neurotransmitters in the brain. The method can be applied to conscious and unrestrained animals and is very suitable for the study of the chemistry of endogenous behaviour. This article reviews the contribution that microdialysis made to our understanding of the chemistry of behaviour. Methodological and practical considerations such as the implantation time and the use of guide cannulas are reviewed. The question whether neurotransmitters and related metabolites in dialysates reflect true synaptic release is critically discussed. There is much evidence that dopamine, noradrenaline, acetylcholine and serotonin in dialysates are related to neurotransmission, but there is serious doubt whether this is the case with amino acid transmitters such as GABA, glutamate and aspartate. Until now far over 100 papers appeared that used microdialysis in behavioural studies. Behavioural activation, the sleep-awake cycle and diurnal rhythms were subject of several of these studies. Various workers have described neurochemical changes in the brain that are related to feeding. Other studies were concerned with sexual behaviour and the sexual cycle in females. Parturition, maternal behaviour and offspring recognition have been studied in a series of microdialysis studies carried out in sheep. An overview is given of the microdialysis studies that were carried out to understand the biochemistry of stress. In this respect dopamine and noradrenaline have received much attention. A great number of microdialysis studies dealt with the role of dopamine in self-stimulation, reward and aversive emotions. It is concluded that microdialysis is at presently the most versatile and practical method to study the chemistry of behaviour and it is to be expected that it will soon be a routine methodology in behavioural research. Finally, perspectives and possible future developments of the methods are discussed.

Animals↗

Stereotyped behaviour, hyperaggressiveness and "tyrannic" hierarchy induced in bank voles (Clethrionomys glareolus) by a restricted cage milieu.

This investigation was originally conceived as a further development of studies made with the "amphetamine model" of psychosis. Since amphetamine itself seemed to be the most important flaw in this model, it was judged promising to study abnormal behaviour in animals elicited without the use of drugs. Bank voles were placed in two different cage milieux, a restricted milieu approaching usual laboratory conditions for experimental animals, and an enriched milieu offering opportunities for satisfaction of natural behavioural (ethological) needs. During an experimental period of 6 months normal behaviours (known from the ethogram of the bank vole) and abnormal behaviours were recorded in eight 5-min observation periods of each cage. Social structure (hierarchy) was studied by the intruder method and social function (peaceful or tyrannic hierarchy) by inspection of the subordinate voles for wounds. Stereotypies, hyperaggressive behaviour and tyrannic hierarchy, replacing normal behaviour and social structure, were seen frequently in the restricted milieu, but only occasionally in the enriched milieu (differences highly significant). It is concluded that these findings indicate possibilities for further development of the basic studies of abnormal behaviour made by means of the "amphetamine model" of psychosis. Opportunities exist for investigation of the interaction of milieu factors with genetic, pharmacological and other factors relevant to the development, prevention and treatment of abnormal behaviour and mental disease.

Aggression↗

Eegraphic and behavioural effects of ondansetron, a 5HT3 antagonist, in rabbits.

1. EEGraphic and behavioural effects of ondansetron, a 5HT3 antagonist, have been studied in the rabbit. Subsequently we tested the neurophysiological and behavioural interactions between ondansetron and L-5-HTP induced serotonergic syndrome. 2. The drug produced a dose-dependent (0.001, 0.01, 0.1 mg/kg i.v.) increase in the cortical power density spectrum, particularly in the range of the lowest frequencies bands. This effect is expression of cortical synchronization. 3. The lowest and mild dose, but not the highest, failed to produce behavioural sedation and to inhibit the arousal induced by vibroacustical stimulation. 4. L-5-HTP (10 mg/kg i.v.) administration generated a typical EEGraphic-behavioural pattern characterized by a decrease of cortical power spectrum density and stereotyped movements. The EEGraphic effects were significantly suppressed by administration of mild and higher doses of ondansetron, while the behavioural effects were inhibited by all doses tested. 5. It is concluded that ondansetron acts with considerably efficacy on central nervous system. The administration of low and mild doses shows a singular dissociation between EEGraphic and behavioural actions. The inhibition of the L-5-HTP behavioural syndrome by ondansetron suggests that this drug acts on behaviour only when there is an altered physiological pattern.

5-Hydroxytryptophan↗

Scratching behaviour in arthritic rats: a sign of chronic pain or itch?

In a previous study, it was shown that adjuvant-induced arthritic rats present an abnormal behaviour pattern up to 60 days after inoculation with Mycobacterium butyricum. The purpose of the present study was to investigate how long the abnormal behaviour pattern continues, and whether the observed increased scratching behaviour is a parameter of chronic pain or rather a reaction to itch. Adjuvant-induced arthritic rats were observed for up to 180 days after the inoculation and their behaviour was quantitatively analysed. The following behavioural changes persisted for more than 60 days: rearing, running and climbing were decreased while grooming, scratching, biting and freezing were increased. No behavioural changes were observed 120 days after the inoculation. The increased scratching was not influenced by an antihistamine drug (astemizole). Not only morphine but also acetylsalicylate selectively depressed the increased scratching behaviour without influencing the other behaviours. These results reinforce the notion that in arthritic rats the increased scratching is a sign of chronic pain.

Animals↗

Differential effects of beta-endorphin infused into the hypothalamic preoptic area at various phases of the male rat's sexual behaviour.

Beta-Endorphin, infused into the pre-optic/anterior hypothalamus (40 pmoles bilaterally) of the male rat before he was placed in an arena containing an oestrous female, inhibited mounting, intromitting and ejaculation, but investigative behaviour continued at control levels. If the infusion was delayed until the male had made an intromission, then beta-endorphin no longer had any effect on sexual interaction, the male mounting and ejaculating as if he had received a control infusion of artificial cerebrospinal fluid. However, if the male was returned to a different female after the infusion had been completed, then the suppressive effects of beta-endorphin returned. Males infused during the refractory period following an ejaculation (and returned to the same female) showed unimpaired return of sexual activity. Imposing a delay of up to 2 h after an intromission and an infusion showed that the effect of beta-endorphin was still antagonized when the male was again paired with the same female; however, by 6 h, its inhibitory effects were beginning to return. Allowing the male to mount (but not intromit) a female whose vagina had been taped partially counteracted the behavioural effect of beta-endorphin. If the female was separated from the male by a small wire cage which allowed limited interaction with her, subsequently infusing the males with beta-endorphin suppressed their mounting behaviour. These results show that both investigative and mounting behaviour can occur after infusions of beta-endorphin into the pre-optic/anterior hypothalamus, but that the transition between them is prevented if infusions are made before a critical point in the behavioural sequence. This is the onset of following the female and mounting her. Analysis of the behavioural sequence after either artificial cerebrospinal fluid or beta-endorphin infusions confirmed this; beta-endorphin interrupted the sequence at the first transition between investigative and mounting behaviour. These results suggest that beta-endorphin acts on a neural mechanism in the medial preoptic area/anterior hypothalamus which allows matching of incentive stimulus to specific behavioural response, and this may be a general property of this part of the brain.

Animals↗

Molecular genetic approaches to understanding brain development and behaviour.

An understanding of brain development and brain function at the level of the genome is developing rapidly, because of the availability of new technologies in molecular and cellular biology. This understanding can be further enhanced by an interactive exchange between the disciplines of behavioural neuroscience and molecular genetics. New genes are being cloned almost daily, but their function remains an enigma. The purpose of this review is to illustrate how reporter genes can be used to map the brain's genetic activity in developmental time and anatomical space. The production of mutants in the homozygous condition may further lead to a morphological or behavioural phenotype. A knowledge of behavioural neuroscience can provide a prescreen of the reporter distribution and thereby make predictions concerning the type of behavioural analysis required. This approach allows selective cloning and sequencing of those genes which have either a morphological or behavioural phenotype but are transcribed at low levels. It is known that genomic imprinting influences brain development, and also that human genetic mutations and deletions influence imprinting in mental retardation as well as certain behavioural disorders. Precisely how such imprinted genes influence brain development and behaviour is being pursued by the use of chimeras. The distribution of maternal or paternal disomy cells in the brain and the way they influence behaviour may reveal the phenotype and how this is brought about.

Alleles↗