Characterization of nicotinic acetylcholine receptor-mediated [H-3]-dopamine release from rat cortex and striatum

The objective of this study was to use a new high throughput method to comp are nicotinic acetylcholine receptor (nAChR)mediated [H-3]-dopamine (DA) re lease from slices of rat striatum and cortex. (-)Nicotine, (-)-cytisine, 1, 1-dimethyl-4-phenylpiperazinium (DMPP), and (+/-)-epibatidine evoked releas e of striatal [3H]-DA with pEC(50) values of 6.7, 8.25, 5.11, and 9.08, res pectively. The same agonists evoked release of cortical [H-3]-DA with pEC(5 0) values of 6.98, 8.06, 5.58, and 9.59. Relative to (-)-nicotine, (-)-cyti sine was a partial agonist in both tissues. In contrast, the maximal respon se evoked by DMPP differed between the two tissues. The rank order of poten cy for antagonists to block DA release was the same (mecamylamine (Mec) > d ihydro-beta -erythroidine (DH betaE) > hexamethonium (Hex) > D-tubocurarine (D-TC)); however, the pIC(50) values varied between the two regions. Where as Mec potently antagonized (-)-nicotine-evoked DA release similarly from s triatum and cortex, with pIC(50) values of 6.07 and 6.53 respectively, the values obtained for DH betaE, D-TC and Hex differed. Additionally, the pres ent study was able to distinguish exocytotic vesicular-mediated from transp orter-mediated DA release, by altering temperature of the incubation and ex clusion of calcium. Assays carried out under these conditions indicate that approximately 60% of nicotine-evoked cortical DA release was likely mediat ed through the DA transporter. In contrast, under the same conditions only 15%-20% of striatal release appeared to be transporter-mediated. We conclud e that the relative contributions of the mechanisms by which (-)-nicotine e vokes DA release differ between striatum and cortex. In addition, the data suggest that the subtypes of nAChRs involved in regulating [H-3]-DA release may be somewhat different in the two tissues. (C) 2000 Elsevier Science Lt d. All rights reserved.