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.