The Effects of the Selective Kappa Antagonist Nor-Binaltorphimine on Dopaminergic Systems of the Rat Brain and Posterior Pituitary
La Vigne, Suzette D.
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The specific effects of a selective kappa opioid-receptor antagonist nor-binaltorphimine (nor-bni) on the activity of nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophysial dopamine (DA) neurons were examined in the rat brain and posterior pituitary. The ability of U50488, a selective kappa opioid agonist, to reverse the effects of nor-bni was also investigated in order to determine if nor-bni was acting specifically at a kappa receptor. DA neuronal activity was estimated by measuring: (1) DA synthesis (dihydroxyphenylalanine (DOPA) accumulation after the administration of an aromatic amino acid decarboxylase inhibitor), (2) DA metabolism (dihydroxyphenylacetic acid (DOPAC) concentrations), and (3) plasma levels of prolactin and a-MSH, hormones know to be regulated by tuberoinfundibular and tuberohypophysial DA neurons , respectively. Nei ther U50488 or nor-bni had any effect on the activity of nigrostriatal or mesolimbic DA neurons, indicating that these neurons are not regulated by kappa receptors. Tuberoinfundibular DA neurons were activated by nor-bni, but this effect was not reversed by U50488 and therefore represents a non-specific action of nor-bni. Tuberohypophysial DA neurons are also activated by nor-bni, and this effect was reversed by U50488, revealing a kappa receptor-mediated tonic inhibition of tuberohypophysial DA neurons.With honors.