Amphetamine enhances latent dopaminergic neurotransmission in the rat striatum. Effects on 3H-acetylcholine release

The electrically evoked, calcium-dependent release of 3H-acetylcholine from slices of rat striatum was inhibited in a concentration-dependent manner by (+)-amphetamine (0.2-20 microM). This inhibitory effect of (+)-amphetamine was unaffected by depletion of the endogenous stores of dopamine by pretreatment with reserpine (5 mg/kg, 24 h). However, the combined treatment of reserpine with alpha-methyl-p-tyrosine (300 mg/kg) or NSD 1015 (100 mg/kg) reduced significantly these inhibitory effects of (+)-amphetamine. Similar results were obtained after chronic 6-hydroxydopamine lesions of the corpus striatum. The inhibition of 3H-acetylcholine release by (+)-amphetamine in rats pretreated with reserpine was potentiated in the presence of 10 microM pargyline. These results support the view that the inhibitory effects of (+)-amphetamine on the electrically-evoked release of 3H-acetylcholine are mediated by dopamine released from a special pool of newly synthetized transmitter rather than through a direct action on an amphetamine recognition site or receptor.