[3H]Nicotine binding in rat brain: alteration after chronic acetylcholinesterase inhibition

(+/-)-[3H]Nicotine binds specifically to rat brain membranes. The binding is stereospecific, (+)-nicotine being 57 times less potent than (-)-nicotine in displacing labeled (+/-)-nicotine. Saturation binding experiments revealed the presence of two binding sites with dissociation constant (Kd) values of 23.7 and 590 nM, and binding site density (Bmax) values of 76 and 646 fmol/mg of protein, respectively. The substrate specificity of the binding site suggests that it represents the nicotinic cholinergic receptor. [3H] Nicotine binding was found to be highest in the hypothalamus and hippocampus and lowest in the cerebellum. Chronic treatment with the acetylcholinesterase inhibitor disulfoton (2 mg/kg/day for 10 days) decreased the number of cholinergic muscarinic and nicotinic binding sites in rat brain. Moreover, the antinociceptive effect of nicotine was found to be markedly reduced in rats chronically treated with disulfoton.