Nicotine Addiction and Impulsive Behaviour: Disentangling the Relationship

Abstract

Drug addiction can now be considered a global epidemic with considerable psychological, physical, social and economicc osts. Substantial research remains focused upon furthering our understating of the disorder, for which current treatments are limited in their effectiveness. More recently there has been an increased interest in the multidimensional construct of impulsivity and its association with addiction. Impulsivity is a hallmark feature of drug addiction, with drug users frequently displaying a preference for immediate over delayed gratification (impulsive choice) and a loss of inhibitory control (disinhibition) (Madden et al.,1997). To date, our understanding of the complex association between impulsivity and drug addiction has been hindered by the cross sectional nature of the majority of research conducted. As a result of this it has been unclear whether impulsivity is a risk factor or a consequence of drug abuse. The experiments of this thesis were primarily concerned with exploring the latter of these theories, in the hope of elucidating the role of drug induced impulsivity in the establishment maintenance and relapse of drug dependence. This was achieved by exploring the effects of nicotine in two animal paradigms of impulsivity; the delayed reward paradigm which assessed impulsive choice,and the symmetrically reinforced go/no-go visual discrimination task which measured behavioural disinhibition. A series of preliminary experiments confirmed the suitability of both tasks for exploring the relationship between impulsivity and nicotine dependence. Behavioural disinhibition in the go/no-go task was stable, lacked sensitivity to changes in primary motivation and furthermore appeared not to be dependent on timing mechanisms. Impulsive choice in the delay discounting task was stable and delay sensitive. Whilst decreasing primary motivation was without effect on impulsive choice, increasing motivation for food reward was found to reduce levels of impulsivity. Acutely, nicotine increased both disinhibition (0.5mg/kg,s .c .) and impulsive choice (0.125,0.25,0.5mg/kg,s .c .). The acute effects of nicotine on both components of impulsivity were effectively antagonised by the centrally acting antagonism tecamylamine which alone was without effect in either model. Adopting a longitudinal design, the effects of chronic nicotine administration (3.16mg/kg/day for seven days, osmotic mini pumps), nicotine withdrawal and the residual sensitivity to nicotine following a sustained period of abstinence were then explored. Chronic nicotine administration enhanced disinhibition and impulsive choice, an effect that was greatest at the initial stages of treatment, suggesting that drug tolerance may have developed. Nicotine withdrawal had differential effects on impulsive choice and disinihibition. In the delay discounting task both initial and long-term withdrawal was associated with enhanced sensitivity to delayed reward. This effect, however, was restricted to low "trait" impulsive animals. Conversely, initial withdrawal induced a short-lived rebound increase in inhibitory control, following which a gradual decreasein inhibitory control was observed that reached significance during the second week of withdrawal. Evidence that the effects of nicotine on impulsivity were temporary was shown, with behaviour returning to base line levels three weeks following termination of treatment. Finally, acute nicotine challenges (0.125,0.25,0.5mg/kg, s. c. ) demonstrated that chronic nicotine exposurer endered animals hypersensitive to the effects of nicotine on disinhibition. Overall the present experimental investigations provide evidence to suggest that impulsivity may be a key componenant both the initial and end stages of addiction. Behavioural and pharmacological treatments that target impulsivity may prove to be effective future treatments for the disorder