Comparison of cigarette, little cigar, and waterpipe tobacco smoke condensate and e-cigarette aerosol condensate in a self-administration model

Abstract

The pharmacological effects of tobacco products are primarily mediated by nicotine; however, research suggests that several non-nicotine tobacco constituents may alter the reinforcing effects of nicotine. This study evaluated the reinforcing effects of aqueous solutions of smoke/aerosol condensate from cigarettes, little cigars, electronic cigarettes (e-cigarettes), and waterpipe tobacco in a self-administration procedure to determine if abuse liability of these tobacco products differed. Adult male Sprague-Dawley rats (n = 64 total) were trained to self-administer intravenous nicotine (30 μg/kg/infusion) on a fixed ratio 5 schedule of reinforcement. Following nicotine dose-effect assessment (1, 7.5, 15, and 30 μg/kg/infusion), rats were given access to smoke/aerosol condensate derived from their assigned tobacco product. Rats responded for smoke/aerosol condensate containing 1, 7.5, 15, and 30 μg/kg/infusion nicotine, with the ratio of nicotine:non-nicotine constituents held constant across doses for each tobacco product. Responding for nicotine or smoke/aerosol condensate was also assessed on a progressive ratio schedule of reinforcement. Cigarette, little cigar, and e-cigarette smoke/aerosol condensates shifted the nicotine dose-effect curve leftward, whereas waterpipe tobacco smoke condensate shifted the dose-effect curve rightward. Smoke/aerosol condensate from all tobacco products produced similar levels of responding compared to nicotine alone during the progressive ratio phase. Results suggest that non-nicotine constituents in cigarettes, little cigars, and e-cigarettes differentially enhance nicotine’s reinforcing potency. In contrast, waterpipe tobacco blunted nicotine’s reinforcing potency, suggesting that it may contain unique constituents that dampen nicotine’s reinforcing effects.

Comparison of the Relative Abuse Liability of Electronic Cigarette Aerosol Extracts and Nicotine Alone in Adolescent Rats: A Behavioral Economic Analysis

“…The current findings are consistent with our previous studies indicating the similar acquisition and elasticity of demand for nicotine alone and EC liquid in adult rats [9,12], as well as findings from another lab indicating a similar reinforcing efficacy for a different EC aerosol extract and nicotine alone under a progressive ratio schedule of reinforcement in adults [25]. That study also found similar SA of nicotine alone and EC extract under the FR 5 schedule of reinforcement at three of the four nicotine unit doses studied [25]. Overall, these data contrast with some findings indicating greater reinforcing effects of cigarette smoke extract compared to nicotine alone in adults [25,41,51], suggesting that cigarette smoke may have greater abuse liability than EC aerosol.…”

“…That study also found similar SA of nicotine alone and EC extract under the FR 5 schedule of reinforcement at three of the four nicotine unit doses studied [25]. Overall, these data contrast with some findings indicating greater reinforcing effects of cigarette smoke extract compared to nicotine alone in adults [25,41,51], suggesting that cigarette smoke may have greater abuse liability than EC aerosol. The unique constituent profile of cigarette smoke, which includes higher levels of several behaviorally active non-nicotine constituents than are present in EC liquid or aerosol (e.g., volatile organic compounds such as acetaldehyde) (e.g., [52][53][54]), presumably accounts for this difference.…”

“…The unique constituent profile of cigarette smoke, which includes higher levels of several behaviorally active non-nicotine constituents than are present in EC liquid or aerosol (e.g., volatile organic compounds such as acetaldehyde) (e.g., [52][53][54]), presumably accounts for this difference. However, one study showed no difference in the reinforcing efficacy between cigarette smoke extract and EC aerosol extract when they were substituted for nicotine alone under a progressive-ratio schedule [25]. Further studies are needed using other models to provide a more comprehensive comparison of the relative abuse liability of cigarette smoke and EC aerosol.…”

“…In addition, despite our use of a relatively high nicotine unit dose, nicotine intake in the current SA model may not have been sufficient to allow any aversive effects to manifest. Further evaluation of EC extracts in SA models that exploit nicotine's aversive effects (e.g., dose escalation models) is needed to examine further the relevance of the reduced aversive effects of EC liquids or extracts seen in ICSS or CTA assays to their reinforcing effects [25]. On the other hand, differences in SA between an EC aerosol extract and nicotine alone have been shown at a very low nicotine dose (0.0075 mg/kg/inf) [25], suggesting further comparison of the nicotine reinforcement threshold (i.e., the lowest reinforcing dose) for EC aerosols versus nicotine alone is warranted.…”

“…SA in adolescent rats. Recent data indicate a greater SA for EC aerosol extract compared to nicotine alone in adult rats under certain conditions [25], indicating that SA models are sufficiently sensitive for evaluating the abuse liability of EC aerosol extracts (see below for further discussion). In contrast to that study, the current study used a 23 h/day access SA model.…”