Effects of oxotremorine and pilocarpine on striatal acetylcholine release as studied by brain dialysis in anesthetized rats.

1. The effects of oxotremorine and pilocarpine on striatal acetylcholine (ACh) release were investigated using brain microdialysis techniques in urethan-anesthetized rats. 2. Oxotremorine (0.1 and 0.5 mg/kg, IV), a preferential M2 agonist, dose-dependently decreased ACh release in the striatum. On the other hand, pilocarpine, at 5 mg/kg (IV), showed a tendency to decrease ACh release in the striatum but, at 7.5 and 10 mg/kg (IV), significantly enhanced release in a dose-dependent manner. 3. The effect of oxotremorine was blocked by scopolamine (0.1 mg/kg, IV) but not by pirenzepine (10 mg/kg, IV), a selective M1 antagonist. 4. Pilocarpine (10 mg/kg, IV) enhancement of striatal ACh release was not affected by 10 mg/kg pirenzepine, but 5 mg/kg pilocarpine significantly increased ACh release in scopolamine (0.1 mg/kg)-pretreated rats without affecting the release by itself. 5. These results suggest that oxotremorine-induced decrease in striatal ACh release is due to stimulation of presynaptic M2 autoreceptor, and that the increase of striatal ACh release by pilocarpine is mediated by mechanism(s) other than effects on muscarinic ACh receptors.