Abstract

l-Nicotine stimulates a biphasic release of [³H]dopamine from mouse striatal synaptosomes which does not persist after agonist is removed. Approximately 80% of the initial release is transient and disappears with 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 perfusion 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 rates for both phases for agonists,K _i values for antagonists andK _i values for low concentrations of agonists. The results are consistent with both phases being mediated by a single type of receptor. In addition, the effects of chronic nicotine treatment on transient and persistent [³H]DA release were measured. For both phases, release was decreased approximately 15% by chronic infusion of 4.0 mg/kg/hr l-nicotine. Correlation of the results with inactivation of a portion of the receptors rather than a reversible desensitization is discussed.