Abnormal Repetitive Behaviors Research Articles

Striatal opioid peptide content in an animal model of spontaneous stereotypic behavior

Stereotypic behaviors are associated with a broad spectrum of developmental, psychiatric, and genetic disorders. Several lines of evidence indicate that these abnormal repetitive behaviors may be expressed as a consequence of imbalanced activity along the direct and indirect processing pathways of the basal ganglia. Because the activity of these two pathways is modulated, in part, by the neuropeptides dynorphin and enkephalin, we sought to determine whether spontaneous and persistent stereotypy is associated with alterations in striatal neuropeptide content. Specifically, the present study employed radioimmunoassay to measure dynorphin-A and leu-enkephalin content in the dorsolateral striatum of deer mice exhibiting different levels of spontaneous stereotypic jumping. The results indicate significantly decreased leu-enkephalin content and significantly increased dynorphin/enkephalin content ratios in high-stereotypy mice relative to low-stereotypy mice. Moreover, analyses revealed a significant negative correlation between striatal enkephalin content and frequency of stereotypy as well as a significant positive correlation between the dynorphin/enkephalin content ratio and frequency of stereotypy in these mice. These data are consistent with the hypothesis that spontaneous stereotypic behavior is expressed as a consequence of relative hyperactivity along cortico-basal ganglia-cortical feedback circuits involving the direct (facilitative) pathway, but suggest that primary perturbations to the indirect (inhibitory) pathway give rise to such imbalanced activity.

Social and husbandry factors affecting the prevalence and severity of barbering (‘whisker trimming’) by laboratory mice

Barbering—the plucking of fur or whiskers from cagemates or oneself—is a common form of abnormal repetitive behavior in laboratory mice. It is often viewed as a ‘normal’ behavior of particular strains, primarily because it is assumed to represent a dominance behavior. Here, we report on a series of experiments investigating the husbandry and social factors involved in barbering. In Experiment 1, we conducted a large-scale epidemiological study. Barbering was found to be related to a number of environmental factors, including cage design, cage location, cagemate relatedness, and the presence of other barbers in the cage. Thus, instead of barbers suppressing the development of barbering in cagemates, as would be expected if barbers were dominant, the presence of a barber in the cage facilitated the behavior in cagemates. In Experiment 2, we quantified the patterns of hair loss seen in barbered mice. These data confirmed that individual barbers pluck idiosyncratic patterns of fur from their cagemates, and that when there were multiple barbers in a cage the patterns plucked by cagemates were significantly more similar than the patterns plucked by non-cagemates. Thus, barbers appear to be facilitating or learning idiosyncratic patterns from their barbering cagemates. Aspects of these data question the assumption that barbering is a dominance behavior. Therefore in Experiment 3, we directly investigated the relationship between dominance and barbering in C57BL/6J mice. The relative dominance score of a mouse within its cage was unrelated to barbering, and the relative severity of hair loss on a mouse was unrelated to its relative dominance. Barbering, therefore, cannot be considered to be a dominance behavior. Instead, our data indicate that it is most likely a form of abnormal repetitive behavior related to compulsive hair plucking (trichotillomania) in humans. The incorrect assumption that barbering represents an eccentric but benign dominance behavior has allowed the welfare consequences of this behavior to remain unaddressed. Barbering should therefore be considered an important variable both in the assessment of the welfare of individual mice and in experiments addressing the impact of husbandry paradigms upon the behavior and welfare of laboratory mice.

Effects of intrastriatal administration of selective dopaminergic ligands on spontaneous stereotypy in mice

Abnormal repetitive behaviors are often associated with specific developmental, genetic, and neuropsychiatric disorders. Repetitive motor behaviors, often referred to as stereotypies, have been studied extensively as they can be readily induced by certain drugs (e.g., amphetamine). Recent work has shown, however, that such drug-induced models of stereotypy may not accurately reflect the neurobiological perturbations responsible for the spontaneous manifestation of these behaviors. The present study employed the deer mouse model of spontaneous and persistent stereotypy to evaluate the capacity of several selective dopaminergic agonists (apomorphine, SKF81297, and quinpirole) to exacerbate levels of spontaneously emitted stereotypic topographies when administered intrastriatally. Additionally, the effects of intrastriatal administration of the D2R antagonist raclopride on the expression of spontaneous stereotypic jumping were evaluated. No induction or exacerbation of stereotypy was observed following administration of the selective D1- or D2- receptor agonists, and the mixed agonist apomorphine induced hyperlocomotion and excessive grooming but failed to exacerbate spontaneous stereotypy. Thus, a dissociation was observed between spontaneously emitted and drug-induced stereotypy, suggesting significant limitations to the use of dopamine agonist-induced stereotypy as a model of clinical stereotyped movement disorder. Furthermore, an unexpected and statistically significant (P<.05) potentiation of locomotor activity was observed following intrastriatal raclopride administration, suggesting major alterations to the modulatory characteristics of the striatal dopaminergic system in these spontaneously stereotypic animals.

Stereotypies in caged parrots, schizophrenia and autism: evidence for a common mechanism

Spontaneously occurring abnormal behaviors in animals have recently received considerable attention, both in veterinary medicine and as a potential model for abnormal behavior in several human mental disorders. Stereotypies are abnormal repetitive, unvarying, and functionless behaviors that are often performed by captive and domesticated animals housed in barren environments. They closely resemble the stereotypies of autistic and mentally retarded patients, stereotypies of unmedicated chronic schizophrenic patients, certain classes of simple tic in Tourette’s syndrome, and several drug-induced behaviors. However, evidence for a common mechanism has been lacking. Stereotypies in human mental disorders are indicative of profound brain dysfunction involving the basal ganglia, and are associated with pervasive voluntary-motor impairments and psychological distress. Here we show that stereotypy in captive Orange-Wing Amazon Parrots ( Amazona amazonica) is correlated with poor performance on the same psychiatric task (the ‘gambling task’) as stereotypy in autistic and schizophrenic patients. The task measures recurrent perseveration—the tendency to inappropriately repeat responses. Thus, the more stereotypy a parrot performed, the more likely it was to inappropriately repeat itself from trial-to-trial on the task; and the more rapidly it made repeated, but not switched, responses. These results parallel the executive motor impairments seen in human patients, and therefore suggest that, like in human patients, stereotypy in caged parrots reflects a general disinhibition of the behavioral control mechanisms of the dorsal basal ganglia. If this result holds true in other laboratory species, stereotypic animals are likely to be of questionable utility in behavior, neuroscience, and neuropharmacological experiments. In humans, stereotypies and obsessive–compulsive behaviors are considered to be mutually exclusive categories of behavior, with different neural substrates, and different treatment strategies. These results, therefore, suggest that the pharmacological treatment of stereotypies in veterinary medicine based on the assumption that they are equivalent to human Obsessive–Compulsive Disorder may be inappropriate. As stereotypies in captive animals develop in response to the captive environment, these results also emphasize the role that the environment may play in eliciting or exacerbating stereotypy in human patients. Finally, by parallel to human patients, there is a potential psychological distress in animals showing these behaviors.

Selective blockade of spontaneous motor stereotypy via intrastriatal pharmacological manipulation

Abnormal repetitive behavior, including stereotypy, is often observed in conjunction with developmental, neuropsychiatric, and genetic disorders. The present work employed the deer mouse model of spontaneous and persistent stereotypy to identify basal ganglia involvement in the mediation of these abnormal behaviors. To evaluate the hypothesis that stereotypy is expressed in these mice due to alterations in the activity of cortico-basal ganglia motor circuits, intrastriatal pharmacological manipulations aimed at attenuating the spontaneously emitted stereotypy were performed. Bilateral striatal infusion of the NMDA or dopamine D 1 receptor antagonists MK-801 or SCH23390, respectively, produced a substantial reduction in levels of stereotypic jumping without inhibiting nonstereotypic motor behavior. These findings support the hypothesis that environmentally related stereotypy is expressed as a consequence of elevated feedback activity occurring along motor circuits of the basal ganglia.

Development of spontaneous stereotyped behavior in deer mice: Effects of early and late exposure to a more complex environment

Abnormal repetitive behaviors such as stereotypies are associated with neurodevelopmental disorders and are often observed under conditions of environmental restriction, particularly early in development. Few studies, however, have systematically assessed the effects of environmental enrichment and almost no information is available as to whether a sensitive period exists for such enrichment effects. We hypothesized that spontaneous stereotypies exhibited by deer mice housed under standard laboratory conditions were the result of environmental restriction and that a sensitive period exists for the development/prevention of stereotypies. Exposure to a more complex environment early in the post-weaning period resulted in substantially less stereotypy in the complex environment. Importantly, this outcome was maintained even after mice were housed in standard cages for an identical period of time. Later exposure to the more complex environment also resulted in significantly lower levels of stereotypy compared to controls. These effects were observed in the experimental housing condition as well as in a standard test context. The effects of early and late enrichment support the importance of environmental restriction in the genesis of stereotypye and provide support for the efficacy of early and late enrichment in the prevention of stereotypies. © 2000 John Wiley & Sons, Inc. Dev Psychobiol 37: 100–108, 2000

Development of spontaneous stereotyped behavior in deer mice: Effects of early and late exposure to a more complex environment

Abnormal repetitive behaviors such as stereotypies are associated with neurodevelopmental disorders and are often observed under conditions of environmental restriction, particularly early in development. Few studies, however, have systematically assessed the effects of environmental enrichment and almost no information is available as to whether a sensitive period exists for such enrichment effects. We hypothesized that spontaneous stereotypies exhibited by deer mice housed under standard laboratory conditions were the result of environmental restriction and that a sensitive period exists for the development/prevention of stereotypies. Exposure to a more complex environment early in the post-weaning period resulted in substantially less stereotypy in the complex environment. Importantly, this outcome was maintained even after mice were housed in standard cages for an identical period of time. Later exposure to the more complex environment also resulted in significantly lower levels of stereotypy compared to controls. These effects were observed in the experimental housing condition as well as in a standard test context. The effects of early and late enrichment support the importance of environmental restriction in the genesis of stereotype and provide support for the efficacy of early and late enrichment in the prevention of stereotypies.

Varieties of repetitive behavior in autism: comparisons to mental retardation.

Systematic study of abnormal repetitive behaviors in autism has been lacking despite the diagnostic significance of such behavior. The occurrence of specific topographies of repetitive behaviors as well as their severity was assessed in individuals with mental retardation with and without autism. The occurrence of each behavior category, except dyskinesias, was higher in the autism group and autistic subjects exhibited a significantly greater number of topographies of stereotypy and compulsions. Both groups had significant patterns of repetitive behavior co-occurrence. Autistic subjects had significantly greater severity ratings for compulsions, stereotypy, and self-injury. Repetitive behavior severity also predicted severity of autism. Although abnormal repetition is not specific to autism, an elevated pattern of occurrence and severity appears to characterize the disorder.

Neurobehavioural Correlates of Abnormal Repetitive Behaviour

Conditions in which echolalia and echopraxia occur are reviewed, followed by an attempt to elicit possible mechanisms of these phenomena. A brief description of stereotypical and perseverative behaviour and obsessional phenomena is given. It is suggested that abnormal repetitive behaviour may occur partly as a result of central dopaminergic dysfunction.

Neurobehavioural correlates of abnormal repetitive behaviour.

Conditions in which echolalia and echopraxia occur are reviewed, followed by an attempt to elicit possible mechanisms of these phenomena. A brief description of stereotypical and perseverative behaviour and obsessional phenomena is given. It is suggested that abnormal repetitive behaviour may occur partly as a result of central dopaminergic dysfunction.