Nicotine and Tobacco Particulate Self-Administration: Effects of Mecamylamine, SCH23390 and Ketanserin Pretreatment
Katharine A. Brennan, Fraser Putt, Vicky Roper, Uta Waterhouse and Penelope TrumanAffiliation:
Victoria University, School of Psychology, P.O. Box 600, Wellington 6140, New Zealand.
AbstractAqueous tobacco particulate matter (TPM) is a tobacco smoke extract that contains nicotine and a number of other smoke constituents, thus TPM self-administration in rats might better represent the more complex pharmacological effects of smoke. The present study sought to examine the effects of several receptor antagonists on nicotine and TPM self-administering rats to compare underlying neurochemical systems involved in maintaining self-administration. Male Sprague Dawley rats were implanted with indwelling jugular catheters for self-administration (n=33). Rats were separated into treatment groups that self-administered nicotine (0.0 or 30.0μg/kg/inf) or cigarette TPM (with matched nicotine content) for a 20-day training period on an ascending fixed ratio schedule. Within subjects dose-response curves were produced (7.5, 15.0, 30.0 and 60.0μg/kg/inf nicotine) for both nicotine and TPM groups. Then the effects of pre-session administration of mecamylamine (0.0, 1.0 and 3.0mg/kg), SCH23390 (0.02mg/kg) and ketanserin (2.0mg/kg) were assessed at each nicotine/TPM dose. The main finding was that nicotine self-administration was attenuated by mecamylamine, SCH23390 and ketanserin pretreatment. TPM-self-administration was comparably attenuated by SCH23390 pretreatment, but was more resilient to the effects of mecamylamine, and was unaffected by ketanserin. Nicotine is the primary driver behind TPM self-administration, thus the non-nicotinic components did not affect baseline behaviour. However, the results from the antagonist trials indicate that differential mechanisms contribute to the reinforcing capacity of nicotine versus TPM.
Ketanserin, mecamylamine, nicotine, tobacco dependence, tobacco particulate matter, SCH23390, selfadministration.
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