BACKWARD WALKING AND CIRCLING: BEHAVIOURAL RESPONSES INDUCED BY DRUG TREATMENTS WHICH CAUSE SIMULTANEOUS RELEASE OF CATECHOLAMINES AND 5‐HYDROXYTRYPTAMINE

Backward walking and circling in rats require simultaneous release of both dopamine and serotonin. A high dose of amphetamine (which releases dopamine) or drugs that release serotonin (p-chloroamphetamine or fenfluramine) each produced these behaviors. Combining smaller doses of amphetamine with either serotonin-releasing drug also triggered backward walking and circling. However, typical dopamine-driven behaviors (rearing, licking, gnawing) from amphetamine were greatly reduced by the serotonin drugs, while typical serotonin-driven behaviors (wet dog shake, hind limb abduction) were unaffected by amphetamine. Fragmentary backward walking and circling from levallorphan were reduced by low-dose amphetamine. The findings strengthen evidence that these movements depend on both dopamine and serotonin release, with possible relevance to hallucinogenic activity, amphetamine psychosis, schizophrenia, and abnormal movements from L-DOPA treatment.

Study at a glance

Abstract

The roles of catecholamine and 5‐hydroxytryptamine (5‐HT) release in mediating backward walking and circling were studied in rats. These behaviours occurred in animals given 15mg/kg intraperitoneally of (+)‐amphetamine (which predominantly releases catecholamines) or either p ‐chloroamphetamine or fenfluramine (which predominantly release 5‐HT). They also occurred when smaller doses of (+)‐amphetamine (5mg/kg) and either p ‐chloroamphetamine (2–5 mg/kg) or fenfluramine (5 mg/kg) were given together. Characteristic dopamine‐dependent behaviours (rearing, licking, gnawing) resulting from (+)‐amphetamine injection were greatly reduced by p ‐chloroamphetamine or fenfluramine. Characteristic 5‐HT‐dependent behaviours (wet dog shake, hind limb abduction) resulting from injection of either p ‐chloroamphetamine or fenfluramine were unaffected by (+)‐amphetamine. Fragmentary backward walking and circling resulting from levallorphan injection (50 mg/kg s.c.) were decreased by (+)‐amphetamine at low dosage. Results in general strengthen previous evidence that backward walking and circling are mediated by simultaneous dopamine and 5‐HT release. The possible relevance of the above findings to hallucinogenic activity, amphetamine psychosis, schizophrenia and abnormal movements due to l ‐DOPA treatment is discussed.