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Neuropsychopharmacology : Official... May 2016Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction, isolated areas of interest, and insistence on sameness....
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction, isolated areas of interest, and insistence on sameness. Mutations in Phosphatase and tensin homolog missing on chromosome 10 (PTEN) have been reported in individuals with ASDs. Recent evidence highlights a crucial role of the cerebellum in the etiopathogenesis of ASDs. In the present study we analyzed the specific contribution of cerebellar Purkinje cell (PC) PTEN loss to these disorders. Using the Cre-loxP recombination system, we generated conditional knockout mice in which PTEN inactivation was induced specifically in PCs. We investigated PC morphology and physiology as well as sociability, repetitive behavior, motor learning, and cognitive inflexibility of adult PC PTEN-mutant mice. Loss of PTEN in PCs results in autistic-like traits, including impaired sociability, repetitive behavior and deficits in motor learning. Mutant PCs appear hypertrophic and show structural abnormalities in dendrites and axons, decreased excitability, disrupted parallel fiber and climbing fiber synapses and late-onset cell death. Our results unveil new roles of PTEN in PC function and provide the first evidence of a link between the loss of PTEN in PCs and the genesis of ASD-like traits.
Topics: Animals; Autistic Disorder; Cerebellum; Female; Male; Mice; Mice, Knockout; PTEN Phosphohydrolase; Purkinje Cells; Social Behavior; Spatial Learning; Stereotyped Behavior
PubMed: 26538449
DOI: 10.1038/npp.2015.339 -
Neuroscience and Biobehavioral Reviews Dec 2017Stereotypic behaviours are commonly observed in captive animals and are usually interpreted as a sign of poor welfare. Stereotypies have also been linked with brain... (Review)
Review
Stereotypic behaviours are commonly observed in captive animals and are usually interpreted as a sign of poor welfare. Stereotypies have also been linked with brain abnormalities. However, stereotypies are a heterogeneous class of behaviours and mounting evidence indicates that different stereotypies can have different causes, and can be linked to different affective states. As a consequence, the implications of a specific stereotypy in a specific species cannot be safely inferred from evidence on other stereotypies or species. Here we review what is known about pacing behaviour in laboratory rhesus macaques, a common stereotypy in this species. Our review highlights the current lack of understanding of the causal factors underlying pacing behaviour. According to current knowledge, the welfare of pacing macaques could be either better, worse or equivalent to that of non-pacing individuals. It is also unclear whether pacing results from brain abnormalities. Since rhesus macaques are widely used as a model of healthy humans in neuroscience research, determining if pacing behaviour reflects an abnormal brain and/or poor welfare is urgent.
Topics: Animal Welfare; Animals; Housing, Animal; Humans; Macaca mulatta; Stereotyped Behavior
PubMed: 28893555
DOI: 10.1016/j.neubiorev.2017.09.010 -
Behavioural Brain Research Jan 2015Spontaneous stereotypic behaviour (SB) is common in many captive animal species, as well as in humans with some severe psychiatric disorders, and is often cited as being... (Review)
Review
Spontaneous stereotypic behaviour (SB) is common in many captive animal species, as well as in humans with some severe psychiatric disorders, and is often cited as being related to general basal ganglia dysfunction. Despite this assertion, there is little in the literature examining SB specifically in terms of the basal ganglia mechanics. In this review, we attempt to fill this gap by offering an integrative, cross-domain perspective of SB by linking what we currently understand about the SB phenotype with the ever-growing literature on the anatomy and functionality of the basal ganglia. After outlining current models of SB from different theoretical perspectives, we offer a broad but detailed overview of normally functioning basal ganglia mechanics, and attempt to link this with current neurophysiological evidence related to spontaneous SB. Based on this we present an empirically derived theoretical framework, which proposes that SB is the result of a dysfunctional action selection system that may reflect dysregulation of excitatory (direct) and inhibitory (indirect and hyperdirect) pathways as well as alterations in mechanisms of behavioural switching. This approach also suggests behaviours that specifically become stereotypic may reflect inbuilt low selection threshold behavioural sequences associated with early development and the species-specific ethogram or, low threshold behavioural sequences that are the result of stress-induced dopamine exposure at the time of performance.
Topics: Animals; Basal Ganglia; Dopaminergic Neurons; Humans; Mesencephalon; Models, Neurological; Models, Psychological; Neural Pathways; Stereotyped Behavior; Stereotypic Movement Disorder
PubMed: 25052167
DOI: 10.1016/j.bbr.2014.05.057 -
Progress in Neuro-psychopharmacology &... Aug 2011Myricitrin is a nitric oxide (NO) and protein kinase C (PKC) inhibitor that has central nervous system activity, including anxiolytic-like action. Nitric oxide...
Myricitrin is a nitric oxide (NO) and protein kinase C (PKC) inhibitor that has central nervous system activity, including anxiolytic-like action. Nitric oxide inhibitors blocked the behavioral effects of apomorphine, suggesting an antipsychotic-like effect. Furthermore, PKC inhibition reduced psychotic symptoms in acute mania patients and blocked amphetamine-induced hyperlocomotion, suggesting a potential antipsychotic-like effect. The present study evaluated the effects of myricitrin in animal models that assess antipsychotic-like effects (apomorphine-induced stereotypy and climbing and the paw test) and extrapyramidal side effects (catalepsy test and paw test). Olanzapine was used as a positive control. 7-Nitroindazole (7-NI), a NOS inhibitor, and l-arginine, a NO precursor, were used to evaluate nitrergic modulation, and tamoxifen was used to test the effect of PKC inhibition. In mice, myricitrin dose-dependently and olanzapine blocked the stereotypy and climbing induced by apomorphine at doses that did not induce catalepsy. 7-Nitroindazole also blocked apomorphine-induced stereotypy and climbing, which were reversed by l-arginine pretreatment. l-arginine only attenuated the effects of myricitrin on apomorphine's effects. Tamoxifen also blocked apomorphine-induced stereotypy and climbing. In the paw test in rats, myricitrin and olanzapine increased hindlimb retraction time at doses that did not affect forelimb reaction time, whereas haloperidol affected both parameters at the same dose. Myricitrin did not induce catalepsy in the bar test. Tamoxifen did not affect hindlimb retraction time or forelimb retraction time, whereas 7-NI significantly increased hindlimb reaction time. Thus, myricitrin exhibited an antipsychotic-like profile at doses that did not induce catalepsy, and this effect may be related to nitrergic action.
Topics: Animals; Antipsychotic Agents; Apomorphine; Arginine; Catalepsy; Disease Models, Animal; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Flavonoids; Indazoles; Male; Mice; Motor Activity; Nitric Oxide; Phytotherapy; Plant Leaves; Plant Preparations; Protein Kinase C; Psychotic Disorders; Rats; Rats, Wistar; Stereotyped Behavior; Syzygium; Tamoxifen
PubMed: 21689712
DOI: 10.1016/j.pnpbp.2011.06.002 -
British Journal of Pharmacology Sep 19821 The relative potencies of dopamine receptor agonists in causing stereotypy in rats when injected into the olfactory tubercles, and contralateral rotation when injected...
1 The relative potencies of dopamine receptor agonists in causing stereotypy in rats when injected into the olfactory tubercles, and contralateral rotation when injected unilaterally into the caudate nucleus of rats with lesions of the nigro-striatal dopamine pathway, were determined. The actions of some agonists in eliciting these responses following peripheral injection, and the relative potencies of dopamine receptor antagonists in inhibiting them were also determined. 2 Dopamine, apomorphine and 2-amino-5,6 and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-5, 6 DTN, A-6, 7 DTN) and N,N dipropyl A-5, 6DTN induced both responses. In contrast, 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine HCl (SK & F 38393) whether injected intracerebrally or peripherally, induced contralateral rotation but not stereotypy. 3 Contralateral rotation and stereotypy induced by apomorphine or N,N dipropyl A-5, 6 DTN were inhibited by haloperidol, pimozide and fluphenazine but these drugs failed to inhibit rotation induced by SK & F 38393. Clozapine inhibited rotation induced by SK & F 38393, apomorphine or N,N dipropyl A-5,6 DTN but failed to inhibit stereotypy. Loxapine was more potent in inhibiting stereotypy than rotation,, whereas clothiapine inhibited rotation and stereotypy at similar doses irrespective of the agonist used to elicit the response. 4 Contralateral rotation induced by SK & F 38393 was not inhibited by yohimbine, prazosin, atropine, methysergide, mepyramine or propranolol. 5 The results provide evidence that contralateral rotation induced by dopamine receptor agonists is mediated by two different classes of dopamine receptors and that these receptors differ from those mediating the stereotypy response. 6 The receptors mediating these responses appear classifiable in terms of their sensitivity to the agonist actions of SK & F 38393 or apomorphine respectively. SK & F 38393-sensitive receptors are susceptible to blockade by clozapine but are not blocked by haloperidol, pimozide or fluphenazine. Apomorphine-sensitive receptors are susceptible to blockade by haloperidol, pimozide and fluphenazine but appear divisible into two sub-classes depending on whether or not they are blocked by clozapine and on their sensitivity to blockade by loxapine.
Topics: Animals; Apomorphine; Behavior, Animal; Humans; Injections, Intraventricular; Male; Rats; Receptors, Dopamine; Rotation; Stereotyped Behavior
PubMed: 6889902
DOI: 10.1111/j.1476-5381.1982.tb09285.x -
Psychopharmacology May 2008Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One...
RATIONALE
Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals produces dorsal striatal activation patterns similar to acute treatment with a high dose of amphetamine.
OBJECTIVES
To extend previous findings of striatal hypersensitivity with behavioral observations and with cellular activity in the nucleus accumbens and prefrontal cortex in sensitized animals.
MATERIALS AND METHODS
Rats treated acutely with 0, 1, 2.5, or 5 mg/kg i.p. amphetamine and sensitized rats challenged with 1 mg/kg i.p. amphetamine were scored for stereotypy, rearing, and grooming, and locomotor activity recorded. c-fos positive nuclei were quantified in the nucleus accumbens and prefrontal cortex after expression of sensitization with 1 mg/kg i.p. amphetamine.
RESULTS
Intense stereotypy was seen in animals treated acutely with 5 mg/kg amphetamine, but not in the sensitized group treated with 1 mg/kg amphetamine. The c-fos response to amphetamine in the accumbens core was augmented in amphetamine-pretreated animals with a shift in the distribution of optical density, while no effect of sensitization was seen in the nucleus accumbens shell or prefrontal cortex.
CONCLUSIONS
A lack of stereotypy in the sensitized group indicates a dissociation of behavioral responses to amphetamine and striatal immediate-early gene activation patterns. The increase in c-fos positive nuclei and shift in the distribution of optical density observed in the nucleus accumbens core suggests recruitment of a new population of neurons during expression of sensitization.
Topics: Amphetamine; Animals; Behavior, Animal; Central Nervous System Stimulants; Dose-Response Relationship, Drug; Genes, fos; Grooming; Immunohistochemistry; Male; Motor Activity; Neurons; Nucleus Accumbens; Prefrontal Cortex; Rats; Rats, Wistar; Recruitment, Neurophysiological; Stereotyped Behavior
PubMed: 18347780
DOI: 10.1007/s00213-008-1100-4 -
Neurotoxicology and Teratology 2021Methylone's rewarding effects have been well characterized; however, little is known about its aversive effects and how such effects may be impacted by sex. In this...
Methylone's rewarding effects have been well characterized; however, little is known about its aversive effects and how such effects may be impacted by sex. In this context, the present study investigated the aversive effects of methylone (vehicle, 5.6, 10 or 18 mg/kg, IP) in 35 male and 31 female Sprague-Dawley rats assessed by conditioned taste avoidance and changes in body temperature and activity/stereotypies. Methylone induced significant taste avoidance, changes in temperature and increased activity and stereotypies in both males and females. Similar to work with other synthetic cathinones, methylone has aversive effects as indexed by significant taste avoidance and changes in temperature and activity (two characteristics of methylone overdose in humans). The only endpoint for which there were significant sex differences was in general activity with males displaying a faster onset and females displaying a longer duration. Although sex was not a factor with taste avoidance and temperature, separate analyses for males and females revealed different patterns, e.g., males displayed a more rapid acquisition of taste avoidance and females displayed changes in temperature at lower doses. Males displayed a faster onset and females displayed a longer duration of activity (consistent with the analyses considering sex as a factor), while time- and dose-dependent stereotypies did not show consistent pattern differences. Although sex differences were relatively limited when sex was specifically assessed as a factor (or only evident when sex comparisons were made in the patterns of effects), sex as a biological variable in the study of drugs should be made to determine if differences exist and, if evident, the basis for these differences.
Topics: Alkaloids; Animals; Avoidance Learning; Body Temperature; Dose-Response Relationship, Drug; Female; Illicit Drugs; Male; Methamphetamine; Motor Activity; Rats; Rats, Sprague-Dawley; Sex Characteristics; Stereotyped Behavior; Taste
PubMed: 33831534
DOI: 10.1016/j.ntt.2021.106977 -
The Journal of Adolescent Health :... Jul 2021To examine how perceptions of gender norms and expressions of empowerment are related among disadvantaged young adolescent boys and girls in Kinshasa, DRC.
PURPOSE
To examine how perceptions of gender norms and expressions of empowerment are related among disadvantaged young adolescent boys and girls in Kinshasa, DRC.
METHODS
We included data from 2,610 adolescent boys and girls between 10 and 14 years old. We examined correlations between three dimensions of perceived gender norms (a sexual double standard, gender stereotypical roles, and gender stereotypical traits) and two domains of agency (voice and decision-making), overall and by sex. We conducted sex-stratified simple and multivariable linear regression models to assess these associations, adjusting for sociodemographic factors. We also tested for differences in the association between gender norm perceptions and agency by sex.
RESULTS
Correlations between gender norm perceptions and agency scores were low (under 0.15). Among boys, greater perception of a sexual double standard was related to more voice (p=0.001) and more decision-making power (p=0.008). Similar patterns were observed among girls for the relationship between sexual double standard and voice (p≤.001), but not for decision-making. Increased perceptions of gender stereotypical traits were related to more voice among girls (p≤.001), while conversely girls who perceived greater gender stereotypical roles had less decision-making power (p=0.010).
CONCLUSIONS
This study demonstrated that gender norm perceptions and agency are distinct but related constructs. Interventions aimed to promote gender equality must consider gender unequal norms and gender-unequal divisions of power as important but different dynamics.
Topics: Adolescent; Adolescent Behavior; Child; Democratic Republic of the Congo; Female; Humans; Male; Sexual Behavior; Stereotyped Behavior; Vulnerable Populations
PubMed: 34217462
DOI: 10.1016/j.jadohealth.2021.03.031 -
Developmental Medicine and Child... Jan 2009The purpose of the study was to count and characterize the range of stereotypies--repetitive rhythmical, apparently purposeless movements--in developmentally impaired...
The purpose of the study was to count and characterize the range of stereotypies--repetitive rhythmical, apparently purposeless movements--in developmentally impaired children with and without autism, and to determine whether some types are more prevalent and diagnostically useful in children with autism. We described each motor stereotypy recorded during 15 minutes of archived videos of standardized play sessions in 277 children (209 males, 68 females; mean age 4y 6mo [SD 1y 5mo], range 2y 11mo-8y 1mo), 129 with autistic disorder (DSM-III-R), and 148 cognitively-matched non-autistic developmentally disordered (NADD) comparison children divided into developmental language disorder and non-autism, low IQ (NALIQ) sub-groups. The parts of the body involved and characteristics of all stereotypies were scored blind to diagnosis. More children with autism had stereotypies than the NADD comparison children. Autism and, to a lesser degree, nonverbal IQ (NVIQ) <80, especially in females contributed independently to the occurrence, number, and variety of stereotypies, with non-autistic children without cognitive impairment having the least number of stereotypies and children with autism and low NVIQ the most. Autism contributed independently to gait and hand/finger stereotypies and NVIQ <80 to head/trunk stereotypies. Atypical gazing at fingers and objects was rare but virtually limited to autism. Stereotypies are environmentally modulated movement disorders, some highly suggestive, but not pathognomonic, of autism. Their underlying brain basis and genetic correlates need investigation.
Topics: Autistic Disorder; Child, Preschool; Female; Gait Disorders, Neurologic; Humans; Intellectual Disability; Intelligence; Language Development Disorders; Male; Neurologic Examination; Play and Playthings; Socialization; Stereotyped Behavior; Stereotypic Movement Disorder; Videotape Recording
PubMed: 19087102
DOI: 10.1111/j.1469-8749.2008.03178.x -
Developmental Medicine and Child... Apr 2010The purpose of this systematic review was to examine the quality of conduct of experimental studies contributing to our empirical understanding of function-based... (Review)
Review
AIM
The purpose of this systematic review was to examine the quality of conduct of experimental studies contributing to our empirical understanding of function-based behavioural interventions for stereotypic and repetitive behaviours (SRBs) in individuals with autism spectrum disorders (ASDs).
METHOD
Systematic review methodology was used to identify relevant articles, to rate the level of evidence and quality of conduct of the studies, and to extract data systematically.
RESULTS
Ten single case studies examining 17 participants (14 males, 3 females; age 2y 11mo-26y) diagnosed with various ASDs were included. Overall, studies reported decreases in SRBs using behavioural interventions and some collateral increase in desirable behaviours.
INTERPRETATION
Only a small number of intervention studies for SRBs explicitly state the function of the behaviour; therefore, relatively little is known about the efficacy of SRB interventions in relation to the range of possible behavioural functions. Evidence supporting SRB interventions is preliminary in nature, and caution should be used in choosing and implementing SRB intervention practices for individuals with ASDs.
Topics: Behavior Therapy; Child; Child Development Disorders, Pervasive; Databases, Factual; Humans; Impulsive Behavior; Stereotyped Behavior; Treatment Outcome
PubMed: 20412248
DOI: 10.1111/j.1469-8749.2009.03597.x