Enhancement of haloperidol-induced catalepsy by nicotine: an investigation of possible mechanisms.
Nicotine has been reported to potentiate the cataleptic effect of the dopamine receptor antagonist haloperidol in rats. This effect is paradoxical, since nicotine alone tends to increase nigrostriatal dopamine release. In the present experiments, a pro-cataleptic effect of nicotine was confirmed statistically but was small and variable. Three potential mechanisms underlying this effect were investigated. (i) Desensitization of brain nicotinic receptors appears to make little if any contribution to the pro-cataleptic effect of nicotine, insofar as the latter was not mimicked by two centrally active nicotinic antagonists (mecamylamine and chlorisondamine). (ii) Depolarization inactivation resulting from combined treatment with haloperidol and nicotine does not appear to be critical, since the pro-cataleptic effect of nicotine was not enhanced by chronic haloperidol administration, a treatment designed to enhance depolarization inactivation. (iii) The slow emergence and persistence of the acute pro-cataleptic effect of nicotine suggested possible mediation by a nicotine metabolite. However, neither cotinine nor nornicotine, the principal pharmacologically-active metabolites of nicotine, exerted a significant pro-cataleptic effect. In conclusion, the pro-cataleptic effect of nicotine was weak and variable in the present study, and its mechanism remains obscure.
Boye
S M
SM
Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada. sboye@pharma.mcgill.ca
Clarke
P B
PB
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced*; D002714:Chlorisondamine / Q000494:pharmacology; D003367:Cotinine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004357:Drug Synergism; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018492:Dopamine Antagonists; D008464:Mecamylamine; D009538:Nicotine; C005311:nornicotine; D006220:Haloperidol; D002714:Chlorisondamine; D003367:Cotinine