A SINGLE (-)-NICOTINE INJECTION CAUSES CHANGE WITH A TIME-DELAY IN THE AFFINITY OF STRIATAL D-2 RECEPTORS FOR ANTAGONIST, BUT NOT FOR AGONIST, NOR IN THE D-2 RECEPTOR MESSENGER-RNA LEVELS IN THE RAT SUBSTANTIA-NIGRA

The in vitro and in vivo effects of (-)-nicotine on dopamine D-2 receptors in the rat neostriatum have been studied using biochemical binding, in situ hybridization and immunocytochemistry. A single i.p. injection (1 mg/kg) of(-)-nicotine resulted in a reduction of the K-D value of the D-2 antagonist [H-3]raclopride binding sites in rat neostriatal membrane preparations at 12 h without any significant change in the B-max value. This action of (-)-nicotine was counteracted by pretreatment 15 min earlier with the nicotine antagonist mecamylamine (1 mg/kg, i.p.). However, the K-D and the B-max values of the D-2 agonist [H-3]NPA binding sites in the rat neostriatal membrane preparations were not significantly affected 0.5-48 h after a single i.p. injection with 1 mg/kg of(-)-nicotine. No significant change in neostriatal D-2 receptor mRNA levels was observed at any time interval after the (-)-nicotine injection. No significant change was observed in tyrosine hydroxylase (TH) immunoreactivity in either the substantia nigra or the neostriatum, nor in nigral TH mRNA levels during the time interval studied (4-24 h posttreatment). Furthermore, addition of low (10 nM) or high (1 mu M) concentrations of(-)-nicotine in vitro to rat neostriatal membranes did not alter the characteristics of [H-3]raclopride or [H-3]NPA binding. These results indicate that a single (-)-nicotine injection can produce a selective and delayed increase in the affinity of D-2 receptors for the antagonist, but not for the agonist without modifying the levels of D-2 receptor mRNA, probably via the activation of central nicotinic receptors.