CHRONIC ANTIDEPRESSANT DRUG-TREATMENT ATTENUATES MOTOR-SUPPRESSANT EFFECTS OF APOMORPHINE WITHOUT CHANGING [H-3] GBR-12935 BINDING

The effects of chronic administration (28 days s.c. via osmotic minipumps) of the antidepressants phenelzine sulphate, desipramine hydrochloride and clomipramine hydrochloride (each at 10 mg/kg per day) on dopamine function have been measured in rats. Both phenelzine and desipramine attenuated the suppression of locomotor activity induced by apomorphine hydrochloride (0.05 mg/kg s.c. 15 min). Clomipramine did not affect the behavioural response to apomorphine. Analyses of brain tissue from these animals using the radioligand [H-3]GBR 12935 revealed that there were no changes in dopamine uptake site density or affinity following the administration of phenelzine, desipramine or clomipramine. Analyses of brain monoamine oxidase activity and tricyclic levels were used to confirm the efficacy of the drug administration protocol. These data indicate that changes in dopamine uptake site density do not mediate antidepressant-induced changes in behavioural responses to apomorphine.