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Boris Gutkin"A Neurocomputational Hypothesis for Nicotine Addiction".

Abstract :

Tobacco addiction is a multistage behavioural process leading to the development of persistent cycles of smoking, craving and relapse.
Chronic smoking has been tied to long-lasting effects of nicotine - the main addictive substance in tobacco smoke - on mesolimbic dopaminergic (DA) signalling pathway. While much is known about the pharmacological action of nicotine in this pathway, there are few answers to the key question of how such effects translate into addictive behavior. Particularly puzzling is the ease with which nicotine addiction is acquired and its persistence, since nicotine appears to have only a limited, or even negative, hedonic impact.

To address some of these issues we present a hypothetical neurocomputational model that combines a set of neural circuits at the molecular, cellular, and system levels and accounts for several neurobiological and behavioral processes leading to nicotine addiction. We propose that combining changes in the nicotinic receptor response, expressed by mesolimbic dopaminergic neurons, with dopamine-gated learning in action-selection circuits, suffices to capture the acquisition of nicotine addiction. We show that an opponent process enhanced by persistent nicotine-taking renders self-administration rigid and habitual by inhibiting the learning process, resulting in long-term impairments in the absence of the drug. The model implies distinct thresholds on the dosage and duration for the acquisition and persistence of nicotine addiction. Our hypothesis unites a number of prevalent ideas on nicotine action into a coherent formal network for further understanding of compulsive drug addiction.

Selected publications

Gutkin B, Ermentrout GB.
Neuroscience: spikes too kinky in the cortex?
Nature. 2006 Apr 20;440(7087):999-1000.

Gutkin BS, Dehaene S, Changeux JP.
A neurocomputational hypothesis for nicotine addiction.
Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1106-11.

Serge Ahmed