A D-1 DOPAMINE AGONIST STIMULATES ACETYLCHOLINE-RELEASE FROM DISSOCIATED STRIATAL CHOLINERGIC NEURONS

We tested the hypothesis that a D-1 dopamine agonist could stimulate a cetylcholine release directly from striatal cholinergic neurons. A sus pension of viable dissociated striatal cells was made enzymatically an d mechanically from normal adult male rats. The heterogeneous suspensi on was incubated in [H-3]choline to allow synthesis of [H-3]acetylchol ine selectively by cholinergic neurons. Fractional [H-3]acetylcholine release from the cholinergic cells in the suspension was recorded duri ng continuous dynamic perifusion. The D-1 agonist, 50 mu M (+/-) SKF 3 8393, increased the basal rate of release from the cholinergic cells b y 50% and the action was inhibited by the D-1 antagonist, SKF 83566. S timulation of [H-3]acetylcholine secretion was recorded as low as 500 nM SKF 38393. The (S,-) SKF 38393 stereoisomer was significantly less effective than the (R,+) isomer in stimulating release. The D-1-mediat ed stimulation of acetylcholine secretion was abolished in a low-calci um environment that also inhibited basal release. The data suggest tha t striatal cholinergic cells express D-1 receptors functionally couple d to the regulation of acetylcholine release. These D-1 actions in the absence of synaptic circuitry imply that such circuitry is not requir ed in situ. In vivo however, indirectly mediated D-1 actions and those of other transmitters may modify the manifestations of this direct ch olinergic stimulation.