CHRONIC NICOTINE TREATMENT COUNTERACTS DOPAMINE D-2 RECEPTOR UP-REGULATION INDUCED BY A PARTIAL MESO-DIENCEPHALIC HEMITRANSECTION IN THE RAT

To further elucidate the previously demonstrated protective actions of nicotine on lesioned nigrostriatal dopamine (DA) systems (Janson and Moller, Neuroscience, 57 (1993) 931-941), the present receptor binding experiments were carried out. Rats were partially hemitransected at t he meso-diencephalic junction and the effects of chronic continuous (- )nicotine treatment (osmotic pumps s.c., 0.125 mg/kg/h, 14 days) on [H -3]N-propylnorapomorphine ([H-3]NPA) and [H-3]methylcarbamylcholine ([ H-3]MCC) binding were investigated in striatal coronal sections to stu dy the agonist binding sites of DA D-2 receptors and nicotinic cholino ceptors, respectively. In saline-treated but not in nicotine-treated r ats, the lesion led to an increased B-max value of [H-3]NPA binding. T he B-max value of [H-3]MCC binding was increased by nicotine treatment and decreased by the partial hemitransection. These results indicate that chronic nicotine treatment counteracts the lesion-induced upregul ation of the high-affinity agonist binding site of the DA D-2 receptor , which may be explained by an increased presence of DA via a protecti ve effect of nicotine on neostriatal DA terminals. This action of nico tine may be of interest in the treatment of neurodegenerative diseases such as Parkinson's disease.