Comparison of dopamine synthesis regulation in the terminals of nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal neurons

Abstract

Summary The rate of accumulation of DOPA after the administration of a decarboxylase inhibitor (NSD 1015) was determined in the striatum, olfactory tubercle, median eminence and posterior pituitary of the rat brain in order to obtain an index of the rate of synthesis of dopamine (DA) in the terminals of nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal neurons, respectively. In all brain regions an increase in the concentration of DA by the administration of a monoamine oxidase inhibitor decreased DOPA accumulation while a decrease in the concentration of DA by the administration of reserpine increased DOPA accumulation. These results indicate that end product inhibition plays a role in regulating DA synthesis in all four neuronal systems. Injections of DA agonists decreased and DA antagonists increased the accumulation of DOPA in striatum, olfactory tubercle and posterior pituitary, but not in median eminence. The administration ofγ-butyrolactone (GBL) and baclofen increased the concentration of DA and the accumulation of DOPA in the striatum, olfactory tubercle and posterior pituitary, and these effects were reversed by the administration of apomorphine. On the other hand, GBL and baclofen had no effect on the concentration of DA or the accumulation of DOPA in the median eminence. These two drugs did, however, reduce theα-methyltyrosine-induced decline of DA in the median eminence suggesting that they inhibit the activity of tuberoinfundibular nerves just as they do DA nerves in other systems. These results suggest that the regulation of DA synthesis in terminals of nigrostriatal, mesolimbic and tuberohypophyseal nerves is different from that in tuberoinfundibular nerves in that the latter nerves appear to lack an autoreceptor regulatory mechanism.