Mecamylamine pretreatment increases subsequent nicotine self-administration as indicated by changes in plasma nicotine level

Abstract

Acute administration of mecamylamine, a centrally active nicotinic cholinergic agonist, has been shown to increase amount of smoking as indicated by smoking topography (e.g., puff rate, puff duration), expired carbon monoxide changes, and other inferential measures. In the present study, subjects showed significantly greater increases in plasma nicotine following smoking of two high-nicotine research cigarettes when pretreated with mecamylamine than when pretreated with placebo, even though no significant differences in puff volume or puff number were detected. Interestingly, none of our subjects reported nausea, although some achieved plasma nicotine levels at which nausea would typically be expected. We attribute the observed increases in nicotine intake to compensatory behavior designed to overcome mecamylamine's blocking effects.

Effects of acute abstinence, reinstatement, and mecamylamine on biochemical and behavioral measures of cigarette smoking in schizophrenia

“…The lack of effects of MEC are consistent with a previous report that acute MEC administration at doses of up to 20 mg/day did not precipitate tobacco withdrawal in dependent cigarette smokers (Eissenberg et al, 1996), and extends the lack of MEC pre-treatment effects on cigarette withdrawal and craving to a subchronic (e.g., six doses over a three day period) dosing paradigm, in which MEC plasma levels presumably reached steady state (the half-life of MEC is ∼10 hours; Young et al, 2001). Several studies in cigarette smokers have demonstrated that acute doses of MEC in the dose range used in the present study (5-10 mg/day) increase cigarette smoking (Stolerman et al, 1973;Nemeth-Coslett et al, 1986;Pomerleau et al, 1987;Rose et al, 2001), suggesting a compensatory increase in smoking behavior in the presence of a nicotinic antagonist. At the first testing session (Day 2AM), SS and CS had received three doses of MEC, but there was no alteration in the amount of cigarettes smoked or in baseline nicotine or cotinine levels.…”

Age-Related Effects of the Nicotinic Antagonist Mecamylamine on Cognition and Behavior

“…Through its action on presumed presynaptic nicotinic receptors, mecamylamine appears to antagonize anticholinester ase-induced release of acetylcholine in vitro (Nordberg et al 1989). Mecamylamine has also been shown to pro duce an increase in cigarette smoking (Stolerman et al 1973;Pomerleau et al 1987), to slow cortical EEG (Pick worth et al 1988), and to block the positive effects of nicotine on learning in monkeys (Elrod et al 1988). We have presented preliminary data suggesting that mecamylamine administered acutely to young healthy males produces impairment of several cognitive processes (Newhouse et al 1992).…”

“…These are doses both below and above that which produce a signifIcant increase in smoking be havior and a measurable drop in BP (Stolerman et a1. 1973;Pomerleau et al 1987).…”

Acute nicotinic blockade produces cognitive impairment in normal humans

“…The doses administered were 5, 10, and 20 mg of mceamylamine and placebo. These are doses both below and above that which produce a significant increase in smoking behavior and a measurable drop in blood pressure (Stolerman et al 1973;Pomerleau et al 1987).…”

“…1989). Mecamylamine has also been shown to produce an increase in cigarette smoking (Stolerman et al 1973;Pomerleau et al 1987), slow cortical EEG (Pickworth et al 1988), and block the positive effects of nicotine on learning in monkeys (Elrod et al 1988). If nicotinic mechanisms are important in human cognitive functioning, mecamylamine may produce measurable cognitive changes at acute doses similar to those which have been shown to produce increases in cigarette smoking.…”