PHARMACOLOGICAL COMPARISON OF TRANSIENT AND PERSISTENT [H-3] DOPAMINERELEASE FROM MOUSE STRIATAL SYNAPTOSOMES AND RESPONSE TO CHRONIC L-NICOTINE TREATMENT

L-Nicotine stimulates a biphasic release of [H-3]dopamine from mouse s triatal synaptosomes which does not persist after agonist is removed. Approximately 80% of the initial release is transient and disappears w ith a half-time of less than 1 min; the other 20% persists for several minutes (t(1/2), 5-10 min). Both the transient and persistent phases were investigated by 10-min exposures to agonists with an in vitro per fusion technique. A series of nicotinic agonists and antagonists were used to determine the pharmacological relationship of the two phases. Parameters measured included EC50 and V-max values and desensitization sensitization rates for both phases for agonists, K-i values for anta gonists and K-i values for low concentrations of agonists. The results are consistent with both phases being mediated by a single type of re ceptor. In addition, the effects of chronic nicotine treatment on tran sient and persistent [H-3]DA release were measured. For both phases, r elease was decreased approximately 15% by chronic infusion of 4.0 mg/k g/hr L-nicotine. Correlation of the results with inactivation of a por tion of the receptors rather than a reversible desensitization is disc ussed.