RELATIONSHIP BETWEEN UP-REGULATION OF NICOTINE BINDING-SITES IN RAT-BRAIN AND DELAYED COGNITIVE ENHANCEMENT OBSERVED AFTER CHRONIC OR ACUTENICOTINIC RECEPTOR STIMULATION

(-)-Nicotine tartrate (2 mg/kg), and a nicotinic agonist, RJR 2403 (1. 4 mg/kg), and antagonist, mecamylamine (1 mg/kg), were administered to separate groups of rats SC twice daily for 10 days. Two other groups received the same doses of nicotine or RJR 2403 for 1 day followed by saline for 9 days. Twenty-four hours after the final injection, the ra ts were compared to a 10-day saline-injected group on acquisition of a hidden platform position in the Morris water maze (20 trials, 30-min inter-trial interval). The rats were killed 48 h after the last drug i njection and frontal, entorhinal and posterior cingulate cortex and do rsal and ventral hippocampus assayed for [H-3]-nicotine binding densit y. Chronic nicotine significantly increased the number of frontal and entorhinal cortical and dorsal hippocampal, but not posterior cingulat e cortical or ventral hippocampal, nicotinic receptors, and improved r ate of learning. Chronic mecamylamine and RJR 2403 also significantly increased the number of nicotinic receptors in frontal cortex, though not other regions, but retarded rate of learning. Nicotine given for 1 day 11 days earlier marginally increased nicotinic receptors in entor hinal cortex (but not other regions) and significantly increased rate of learning, though significantly less than 10-day nicotine. Entorhina l cortical and dorsal hippocampal nicotinic receptor numbers were posi tively associated with rate of learning but not performance at asympto te. Thus cognitive enhancement after chronic nicotine is in part a del ayed consequence of nicotine administration 11 days earlier, and may r eflect regional changes in nicotinic receptor up-regulation.