Intrastriatal kainic acid elicits functional supersensitivity of muscarinic receptors regulating dopamine release

Acetylcholine enhanced in a concentration-dependent way the K(+) (15 mM)-evoked release of [(3)H]dopamine from synaptosomes isolated from rat corpus striatum and prelabeled with the radioactive catecholamine. The concentration-effect curve of ACh obtained in presence of 1.2 mM Ca(2+) was progressively shifted to the left when [Ca(2+)] was lowered to 0.4 and to 0.2 mM. Intrastriatal injections of kainic acid reduced (70%) the uptake of [(3)H]choline in synaptosomes prepared 8 days after the lesion but did not affect significantly the uptake of [(3)H]dopamine. Also the release of [(3)H]dopamine evoked by K(+) was minimally affected by kainic acid treatment. In contrast, acetylcholine (tested in presence of 1.2 or 0.2 mM Ca(2+)) was much more effective in enhancing [(3)H]dopamine release in synaptosomes from kainic acid-lesioned than from unlesioned striata. The results suggest that muscarinic receptors located on dopamine nerve terminals undergo supersensitivity following intrastriatal kainic acid injection.