Role of dopamine in the behavioural actions of nicotine related to addiction

Experimental impairment of dopamine function by 6-hydroxydopamine lesions o r by dopamine receptor antagonists shows that dopamine is involved in nicot ine's discriminative stimulus properties, nicotine-induced facilitation of intracranial self-stimulation, intravenous nicotine self-administration, ni cotine conditioned place-preference and nicotine-induced disruption of late nt inhibition. Therefore, nicotine depends on dopamine for those behavioura l effects that are most relevant for its reinforcing properties and are lik ely to be the basis of the abuse liability of tobacco smoke. On the other h and, in vivo monitoring studies show that nicotine stimulates dopamine tran smission in specific brain areas and in particular, in the shell of the nuc leus accumbens and in areas of the extended amygdala. These effects of nico tine resemble those of a reward like food except that nicotine-induced rele ase of dopamine does not undergo single-trial, long-lasting habituation. It is speculated that repeated non-habituating stimulation of dopamine releas e by nicotine in the nucleus accumbens shell abnormally facilitates associa tive stimulus-reward learning. Acute effects of nicotine on dopamine transm ission undergo acute and chronic tolerance; with repeated, discontinuous ex posure, sensitization of nicotine-induced stimulation of dopamine release i n the nucleus accumbens core takes place while the response in the shell is reduced. It is speculated that these adaptive changes are the substrate of a switch from abnormal incentive responding controlled by consequences (ac tion-outcome responding) into abnormal habit responding, triggered by condi tional stimuli and automatically driven by action schemata relatively indep endent from nicotine reward. These two modalities might coexist, being util ized alternatively in relation to the availability of tobacco. Unavailabili ty of tobacco disrupts the automatic, implicit modality of abnormal habit r esponding switching responding into the explicit, conscious modality of inc entive drug-seeking and craving. (C) 2000 Elsevier Science B.V. All rights reserved.