Enkephalin inhibits dopamine synthesis in vitro in the median eminence portion of rat hypothalamic slices

The effect of enkephalin on dopamine synthesis in vitro in tuberoinfundibular dopaminergic (TIDA) neurons was investigated in rat hypothalamic slices. Dopamine synthesis in vitro in TIDA neurons was estimated by 3,4-dihydroxyphenylalanine (DOPA) accumulation in the median eminence after incubation of slices with a DOPA decarboxylase inhibitor. The enkephalin agonist [D-Ala2]Met-enkephalinamide (ENKamide) decreased the rate of basal DOPA accumulation in the median eminence portion of hypothalamic slices from ovariectomized rats at concentrations over 2 microM. The inhibitory action of ENKamide was more pronounced in hypothalamic slices from haloperidol-treated rats in which basal DOPA accumulation in the median eminence was stimulated by increased PRL secretion. In contrast, ENKamide decreased neither the rate of depolarization- induced CA2+-dependent DOPA accumulation nor the rate of (Bu)2cAMP- or forskolin-induced DOPA accumulation in the median eminence of normal or haloperidol-treated rats. The rank order of the potencies of enkephalins and their analogs for inhibition of DOPA accumulation in the median eminence was similar to that of their binding capacities for opioid receptors. ENKamide inhibited basal DOPA accumulation even when hypothalamic slices were incubated in Ca2+-free medium to which tetrodotoxin was added or when the median eminence was incubated alone without the remainder of the hypothalamic slice. These results suggest that enkephalin, by acting directly on axon terminals of TIDA neurons in the median eminence, inhibits basal dopamine synthesis.