Comparison of the behavioral effects of cigarette smoke and pure nicotine in rats

Abstract

Animal models of tobacco dependence typically rely on parenteral administration of pure nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. The primary goal of this study was to validate methods for administering cigarette smoke to rats using exposure conditions that were clinically relevant and also produced brain nicotine levels similar to those produced by behaviorally active doses of pure nicotine. A secondary goal was to begin examining the behavioral effects of smoke. Nose-only exposure (NOE) to smoke for 10-45 min or whole-body exposure (WBE) to smoke for 1-4 hr produced serum nicotine concentrations similar to those in smokers (14-55 ng/ml), without excessive carbon monoxide exposure. Daily nicotine (0.1 mg/kg, s.c.) induced locomotor sensitization whereas 45-min NOE producing brain nicotine levels within the same range did not. Nicotine 0.125 mg/kg s.c. reversed withdrawal from a chronic nicotine infusion as measured by elevations in intracranial self-stimulation thresholds whereas 4-hr WBE producing similar brain nicotine levels did not. These data demonstrate the feasibility of delivering cigarette smoke to rats at clinically relevant doses, and provide preliminary evidence that the behavioral effects of nicotine delivered in smoke may differ from those of pure nicotine.

The acute effects of tobacco smoking and alcohol consumption on video-lottery terminal gambling

“…Alternatively, it is possible that a combination of nicotine and non-nicotine tobacco constituents is necessary for nicotine to exert an effect on gambling behavior. A growing body of evidence suggests that non-nicotine tobacco ingredients contribute to the addictive properties of tobacco and interact with nicotine to produce tobacco's reinforcing effects (e.g., Barrett, 2010;Barrett and Darredeau, 2012;Clemens et al, 2009;Harris et al, 2010) and it is possible that nicotine-containing tobacco use rather than nicotine per se increases gambling behavior. Finally, because tobacco addicted gamblers likely had considerable previous experience pairing cigarette smoking with VLT gambling, it is possible that cigarette smoking rather than the pharmacological actions of nicotine themselves have come to serve as a conditioned cue for gambling through associative learning processes (see Crombag et al, 2008).…”

“…However, in two recent studies the acute administration of nicotine via inhalers (McGrath et al, 2012b) and lozenges (McGrath et al, 2013) did not impact upon VLT gambling behavior or the desire to gamble. Since the pharmacokinetics of nicotine delivery from inhalers and lozenges differs from nicotine administered through tobacco smoke (Benowitz et al, 2009;Schneider et al, 2008) and since there is growing evidence that nicotine may interact with various non-nicotine tobacco constituents to produce many of the subjective and behavioral effects of smoking (e.g., Barrett, 2010;Barrett and Darredeau, 2012;Clemens et al, 2009;Harris et al, 2010), it remains possible that McGrath et al's negative findings may not extend to the acute administration of tobacco smoke per se.…”

Animal models to assess the abuse liability of tobacco products: Effects of smokeless tobacco extracts on intracranial self-stimulation

“…Surgery, apparatus, and training procedure used here are described in detail elsewhere (Harris et al, 2010, 2011; Roiko et al, 2009). Briefly, animals were anesthetized with i.m.…”

The acute effects of nicotine on the subjective and behavioural responses to denicotinized tobacco in dependent smokers

“…However, a growing body of evidence suggests that non-nicotine smoking factors may also be critical to tobacco addiction. In animal models, the range of conditions that support nicotine self-administration (SA) is much more limited than that for other addictive substances (Matta et al, 2007), nicotine administered apart from tobacco has been shown to have distinct behavioural effects from tobacco smoke (Harris et al, 2010), and the combination of nicotine and certain non-nicotine tobacco ingredients is more readily self-administered than nicotine alone (Clemens et al, 2009). Moreover, there is some evidence that nicotine SA may depend on the presence of pharmacological or nonpharmacological conditioned stimuli (Sorge et al, 2009), and that nicotine may exert many of its effects by increasing the positive reinforcing value of such stimuli (Chaudhri et al, 2007) rather than by having strong primary positive reinforcing properties per se.…”