Relationship between up-regulation of nicotine binding sites in rat brain and delayed cognitive enhancement observed after chronic or acute nicotinic 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 rats 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 injection and frontal, entorhinal and posterior cingulate cortex and dorsal and ventral hippocampus assayed for [3H]-nicotine binding density. Chronic nicotine significantly increased the number of frontal and entorhinal cortical and dorsal hippocampal, but not posterior cingulate cortical or ventral hippocampal, nicotinic receptors, and improved rate 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 entorhinal cortex (but not other regions) and significantly increased rate of learning, though significantly less than 10-day nicotine. Entorhinal cortical and dorsal hippocampal nicotinic receptor numbers were positively associated with rate of learning but not performance at asymptote. Thus cognitive enhancement after chronic nicotine is in part a delayed consequence of nicotine administration 11 days earlier, and may reflect regional changes in nicotinic receptor up-regulation.
Abdulla
F A
FA
Department of Psychology, Institute of Psychiatry, London, UK.
Bradbury
E
E
Calaminici
M R
MR
Lippiello
P M
PM
Wonnacott
S
S
Gray
J A
JA
Sinden
J D
JD
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology*; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine