The effect of p-chlorophenylalanine on the pethidine- or methadone-induced decrease in locomotor activity of rats.

Either pethidine HCl (50 mg/kg s.c.) or methadone HCl (8 mg/kg s.c.) produced a prominent decrease in locomotor activity of rats. Pretreatment of rats with p-chlorophenylalanine (p-CPA, 320 mg/kg i.p.) 48 h before the narcotic injection significantly antagonized the activity-decreasing effects of narcotics. When rats pretreated with p-CPA were given 5-hydroxytryptophan (75 mg/kg s.c.) 30 min before narcotic administration, the activity-decreasing response to narcotics was restored. Thus, a decrease in locomotor activity induced in rats by either pethidine or methadone is probably mediated by serotonergic mechanisms.