TRANSMITTER-LIKE 3,4-DIHYDROXYPHENYLALANINE IS TONICALLY RELEASED BY NICOTINE IN STRIATA OF CONSCIOUS RATS

Microdialysis and high performance liquid chromatography with an electrochemical detector were applied to compare the characteristics of nicotine-evoked release of endogenous 3,4-dihydroxyphenylalanine (DOPA) from striata of conscious rats and those of the release of dopamine (DA). Dialysates were collected every 20 min 3-8 h after the start of perfusion. Nicotine was perfused for 20 min through a probe. (+/-)-Nicotine (100-300 muM) constantly and repeatedly released DOPA and DA over a similar time course in a dose-dependent manner. The ratio of the DOPA and DA release evoked was approximately 1:3. The (+/-)-nicotine (200 muM)-induced DOPA release was mecamylamine (500 muM)-sensitive, tetrodotoxin (100 nM)-sensitive and Ca2+ (removal plus 12.5 mM Mg2+ addition)-dependent. The (+)-isomer produced no DOPA release. These characteristics of DOPA release were almost the same as those of DA release. Furthermore, mecamylamine alone inhibited the basal release of DOPA but not of DA. Nicotine released stereoselectively endogenous DOPA via nicotinic acetylcholine receptors from striata of freely moving rats in a manner similar to transmitter DA. These acetylcholine receptors function tonically for the release of DOPA. These findings are further support for our proposal that DOPA is an endogenous neuroactive substance.