Effect of pilocarpine on striatal acetylcholine release in dopamine-depleted rats

We have previously demonstrated that the systemic administration of pilocarpine stimulates striatal acetylcholine (ACh) release in rats using a brain microdialysis technique. In the present study, we investigated whether a nigro-striatal dopaminergic system is involved in the pilocarpine-induced increase in striatal ACh release using dopamine-depleted rats under urethane anesthesia. The application of pilocarpine (0.1-10 mM) via the microdialysis tube increased striatal ACh release in normal rats in a concentration-dependent manner, but it had no effect on the release of glutamate or gamma-aminobutyric acid (GABA) from the striatum. The increase in striatal ACh release caused by pilocarpine (1 mM) was enhanced by reserpine and alpha-methyl-p-tyrosine treatment, which completely depleted dopamine in the striatum. These results suggest that pilocarpine selectively increases striatal ACh release by acting at the striatum, and that the nigro-striatal dopaminergic neurons play an inhibitory role in the pilocarpine-induced ACh release.