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Vol. 282, Issue 1, 32-43, 1997
Institute for Behavioral Genetics, University of Colorado, Boulder,
Colorado
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
(t1/2, 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 Vmax values
and desensitization rates for both phases for agonists,
Ki values for antagonists and
Ki 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.
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