Effects of chronic antidepressant treatment on nigrostriatal and mesolimbic dopamine autoreceptors in the rat.
Dopamine autoreceptors were studied by determining the effects of chronic antidepressant treatment on the ability of several doses of apomorphine to decrease 3,4-dihydroxyphenylalanine accumulation (an index of dopamine synthesis in vivo) after saline or ?-hydroxybutyric acid lactone (?-butyrolactone). 3,4-Dihydroxyphenylalanine accumulation was measured in nigrostriatal [nucleus caudatus putamen] and mesolimbic [nucleus accumbens and tuberculum olfactorium] nerve terminals. Apomorphine decreased 3,4-dihydroxyphenylalanine accumulation in the nucleus caudatus putamen, tuberculum olfactorium and nucleus accumbens in a dose-related manner. Chronic imipramine (10 days) treatment attenuated the low and high dose apomorphine-induced decrease in 3,4-dihydroxyphenylalanine accumulation in the nucleus caudatus putamen to a greater extent than the tuberculum olfactorium or nucleus accumbens. In ?-butyrolactone-treated animals chronic treatment with imipramine, amitriptyline or bupropion (10 days) attenuated the low dose apomorphine effect in the nucleus caudatus putamen, but not the tuberculum olfactorium or nucleus accumbens. Only 2 days of imipramine treatment had no effect on the apomorphine-induced decrease in 3,4-dihydroxyphenylalanine accumulation in the nucleus caudatus putamen with or without ?-butyrolactone treatment. These data suggest that chronic treatment with three antidepressants produces dopamine autoreceptor subsensitivity in nigrostriatal neurons more than mesolimbic neurons and that this effect is not seen with short-term imipramine treatment.
Nielsen
J A
JA
Department of Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, U.S.A.