The role of mesolimbic dopamine in nicotine dependence

It is now widely accepted that a majority of habitual tobacco smokers becom e addicted to the nicotine present in the smoke. This brief review focuses on the evidence that nicotine exerts on the mesolimbic dopamine (DA) system that are entirely consistent with it having the properties of a psychostim ulant drug of abuse, Thus, the ability of nicotine to reinforce self- admin istration in experimental animals depends upon its ability to stimulate the DA-secreting neurones which project to the nucleus accumbens. Microdialysi s studies show that acute nicotine preferentially stimulates DA overflow in the shell of the nucleus accumbens, whereas subchronic nicotine causes sen sitisation of its stimulatory effects on DA overflow in the core of the str ucture. The presentation discusses the evidence that stimulation of DA over flow in the accumbens shell is required to elicit or, more likely, signal t he 'rewarding' properties of the drug which reinforce self-administration. Based on the results of studies with other psychostimulant drugs, it is pos sible that these effects are mediated by the D-3 receptors that are found i n relatively high density in the subdivision of the structure. The sensitis ed effects of subchronic nicotine in the core of the accumbens are thought to mediate the transfer from 'drug-liking' to 'drug-seeking' behaviour and, therefore, to be of fundamental importance to the development of dependenc e. The nature of the receptor(s) involved remains to be established althoug h there is circumstantial evidence for a role of both D-1 and D-2 receptors . Studies reported in more recent years have suggested that increased DA ov erflow in the accumbens is not, in itself, sufficient to account for the re warding properties of addictive drugs. The review concludes by discussing t he evidence that drugs of dependence preferentially increase DA overflow in to an extra-synaptic compartment where it gains access, by a process of vol ume transmission, to extra-synaptic DA receptors located on adjacent cells. These receptors, it is proposed, facilitate the way in which we learn abou t cues associated with pleasurable stimuli and the ways in which the may be experienced again.