EFFECTS OF CHLORISONDAMINE ON NICOTINIC RECEPTOR-BINDING IN WHOLE-BRAIN AND NICOTINE-INDUCED CHANGES IN LOCOMOTOR-ACTIVITY IN RATS

Chlorisondamine, a nicotinic cholinergic receptor antagonist, can bloc k many of the in vivo effects of nicotine for weeks after a single icv injection. The time course of this effect was examined in a single gr oup of rats by assessing the effects of nicotine on locomotor activity at 1, 3, and 6 weeks after the icv administration of 23 nmol of chlor isondamine. The effects of nicotine on locomotor activity were biphasi c as has been previously reported, with decreases in activity early in the session and increases in activity later in the session. These eff ects of nicotine were blocked in chlorisondamine-treated rats at 1 or 3 weeks but not 6 weeks after administration of chlorisondamine. Nicot inic receptor binding in the brains of chlorisondamine-treated rats re vealed no change in B-max but a significant increase in affinity (47-5 9% decrease in K-d) 1, 3, 6, or 7 weeks after treatment. In contrast t o its effects on affinity when administered icv, chlorisondamine did n ot alter binding affinity when added directly to the incubation buffer in vitro. Thus, although chlorisondamine significantly alters neurona l nicotinic cholinergic receptor binding affinity, this effect of chlo risondamine on binding affinity does not appear to be a direct effect of chlorisondamine on the receptor or to match the time course of chlo risondamine blockade of nicotine-induced changes in locomotor activity . (C) 1994 Wiley-Liss, Inc.