Nicotine and Tobacco Particulate Self-Administration: Effects of Mecamylamine, SCH23390 and Ketanserin Pretreatment

Aqueous 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.