Catalepsy and stereotypies in rats treated with methadone; Relation to striatal dopamine

Abstract

To study methadone-induced catalepsy and stereotyped behaviour, rats were treated for 8 weeks with (±)-methadone. Acute administration of 10 mg/kg of methadone produced catalepsy but no stereotypies in control rats. After 5 weeks of chronic administration methadone still produced dose-dependent catalepsy, the degree of which gradually decreased with continuing treatment. However, all rats showed stereotypies which appeared after 4–5 days and were at their maximum after 5–6 weeks of chronic administration. Naloxone administered before methadone completely prevented the appearance of catalepsy and stereotypy; naloxone administered 0.5–1 hr after methadone abolished the catalepsy and stereotyped symptoms. Reserpine pretreatment prevented the appearance of stereotypies. 2 hr after methadone, 10 mg/kg, the striatal homovanillic acid (HVA) concentration of rats receiving methadone for 8 weeks was increased to about the same degree as in control (saline) rats receiving the same dose of methadone as a single injection; however, 19 hr after the last injection of methadone the striatal HVA concentrations of rats receiving methadone for 8 weeks was decreased to 55% of that of untreated control rats. The results suggest that the primary effect of methadone is catalepsy which causes increased dopamine production as a compensatory mechanism. The additional dopamine is a probable cause of stereotyped behaviour in rats which are partially tolerant to the cataleptic effect of methadone.