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 minipu mps) of the antidepressants phenelzine sulphate, desipramine hydrochlo ride and clomipramine hydrochloride (each at 10 mg/kg per day) on dopa mine function have been measured in rats. Both phenelzine and desipram ine attenuated the suppression of locomotor activity induced by apomor phine hydrochloride (0.05 mg/kg s.c. 15 min). Clomipramine did not aff ect 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 foll owing the administration of phenelzine, desipramine or clomipramine. A nalyses of brain monoamine oxidase activity and tricyclic levels were used to confirm the efficacy of the drug administration protocol. Thes e data indicate that changes in dopamine uptake site density do not me diate antidepressant-induced changes in behavioural responses to apomo rphine.