Enhancement of dopamine-stimulated adenylate cyclase activity in rat caudate after lesions in substantia nigra: evidence for denervation supersensitivity.

Unilateral radiofrequency lesions or chemical lesions with 6-hydroxydopamine were produced in the substantia nigra of rat brain in order to destroy dopaminergic innervations to caudate nucleus and thereby to produce functional denervation supersensitivity. Both types of lesions resulted in enhanced stimulation of caudate adenylate cyclase (EC 4.6.1.1) activity by dopamine at all dopamine concentrations tested, with more marked enhancement at the lower concentrations. Response to another dopamine agonist, 1-(3,4-dihydroxybenzyl)-4-(20pyrimidinyl) piperazine (S584) was also enhanced. 6-Hydroxydopamine lesions resulted in selective enhancement of the dopamine-stimulated component of adenylate cyclase, whereas radiofrequency lesions resulted also in a marked decrease in basal activity. It is postulated that the basal activity of caudate represents primarily an adenylate cyclase distinct from that stimulated by dopamine and destroyed only by the less selective radiofrequency lesion. The enhancement of dopamine-sensitive adenylate cyclase after lesions serves as indirect evidence for a significant role of this system in the transmitter function of dopamine and indicates, furthermore, that it is directly involved in dopamine receptor supersensitivity in vivo produced by denervation.