Nicotine dependence, midbrain dopamine systems and psychiatric disorders.

Compelling evidence exists that tobacco-smoking represents a form of drug addiction to nicotine. Like several drugs of abuse, nicotine activates the mesolimbic dopamine system and this effect appears to be of critical importance for the reinforcing properties of the drug. Specifically, nicotine has been shown to increase burst activity in dopamine neurones of the ventral tegmental area, i.e. a mode of firing pattern in these cells which is physiologically associated with basic motivational processes underlying learning and cognitive behaviour. The stimulatory action of nicotine on mesolimbic dopamine neurones is exerted both at the somatodendritic and at the terminal levels. Yet, the release of dopamine in the nucleus accumbens induced by systemically administered nicotine is abolished by the nicotine receptor antagonist, mecamylamine when administered locally in the ventral tegmental area, but not in the nucleus accumbens. Whereas continuous infusion of nicotine into the ventral tegmental area produces a long-lasting increase in accumbal dopamine release, analogously to the effect of systemically administered nicotine, continuous infusion of nicotine into the nucleus accumbens produces a very short-lasting dopamine release. Thus, nicotinic receptors in the ventral tegmental area appear to be more significant than those located in the nucleus accumbens for mediating the stimulatory effect of nicotine on dopamine release in the nucleus accumbens. The effect of nicotine on midbrain dopamine systems may help to explain the extremely high prevalence of tobacco-smoking in schizophrenics, who frequently display so-called hypofrontality, i.e. a reduced functional activity in the prefrontal cortex which provides a direct input to the ventral tegmental area dopamine cells.(ABSTRACT TRUNCATED AT 250 WORDS)