EFFECTS OF CHLORIMIPRAMINE ON THE SYNTHESIS AND METABOLISM OF DOPAMINE IN THE RAT STRIATUM

In the rat, chlorimipramine (7.5, 15, and 60 mg/kg IP and 15 and 60 mg/kg orally) increased the rate of the striatal in vivo tyrosine hydroxylation measured as the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition. The demethylated metabolite of chlorimipramine desmethylchlorimipramine increased the DOPA accumulation only after a dose of 60 mg/kg IP, but did not significantly change the DOPA accumulation after oral administration. Protriptyline (7.5-30 mg/kg) and benztropine (25 mg/kg) decreased the DOPA accumulation. After inhibition of the impulse flow in the nigroneostriatal pathway by treatment with gammabutyrolactone (GBL), benztropine decreased the DOPA accumulation, while no significant effect was observed after chlorimipramine or protriptyline. Neither chlorimipramine nor protriptyline counteracted the decreased DOPA accumulation after apomorphine in rats treated with GBL. After treatment with reserpine, benztropine decreased the DOPA accumulation. Chlorimipramine and protriptyline did not significantly alter the DOPA accumulation after reserpine. Neither did chlorimipramine or protriptyline counteract the effect of apomorphine on the DOPA accumulation after reserpine. Chlorimipramine (15 mg/kg IP) increased the striatal 3,4-dihydroxyphenylacetic acid (DOPAC) levels, while protriptyline (15 mg/kg IP) had no significant effect. The effects of chlorimipramine on the DOPA accumulation and on the DOPAC levels in the striatum may be mediated directly via central dopamine receptors, but more probably indirectly via central 5-hydroxy-tryptaminergic mechanisms. © 1979 Springer-Verlag.