Exposure to nicotine enhances the behavioral stimulant effect of nicotine and increases binding of [3H]acetylcholine to nicotinic receptors.
Rats were given daily injections of nicotine sulfate in doses ranging from 0.1 to 0.4 mg/kg. The behavioral effect of these injections was measured as locomotor activity in photocell cages. Repeated administration of the same dose to each rat resulted in an enhancement of the stimulant effect of nicotine. This enhanced behavioral effect was quite pronounced within 5 days of repeated injection. Tissue from the cerebral cortex of these rats, exposed to nicotine for 5 days, was assayed for binding of [3H]acetylcholine to nicotinic receptors. These relatively small doses of nicotine resulted in 18-26% increases in cortical nicotinic receptors, compared to saline-treated rats. Rats exposed to 0.2 mg/kg of nicotine for 5 days and then given saline for 7 days still showed an enhanced behavioral response to nicotine on the eighth day after exposure, and nicotinic binding in the cortex was still elevated. However, 21 days after exposure to nicotine both the behavioral response to nicotine and the binding values had returned to the same values as those of saline-treated rats. These data imply that increased binding of [3H]acetylcholine to nicotinic sites and the enhanced behavioral effect of nicotine are functionally linked.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D013997:Time Factors
D011978:Receptors, Nicotinic; D009538:Nicotine; D000109:Acetylcholine