SEROTONERGIC INVOLVEMENT IN BEHAVIORAL-RESPONSES TO AMPHETAMINE AT HIGH DOSAGE

Administration of 15 mg/kg d-amphetamine to rats caused increased motor activity of normal type (forward locomotion, rearing) and stereotyped behaviour (head swaying, gnawing). Motor activity of abnormal type (backward locomotion, circling) also occurred. The latter activities were increased when 5-hydroxytryptamine (5HT) synthesis was increased by tryptophan administration and were decreased by the inhibitor of 5HT synthesis p-chlorophenylalanine, by the 5HT receptor blockers metergoline and cyproheptadine, by fluoxetine (which inhibits uptake of drugs into 5HT neurons) and by the dopamine receptor blocker α-flupenthixol. Therefore, the backward locomotion and circling appear to be activated by dopamine and 5HT released by d-amphetamine at high dosage. Effects of the above drugs on motor activities of normal type and gnawing provoked by amphetamine on the whole suggest that these behaviours although activated by dopamine are inhibited by 5HT. © 1979.