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.