Dopamine/dopaminergic system nicotine

Indirect mechanisms Nicotine has indirect effects on monoamine systems. A considerable amount of research has examined the relationships between nicotine and dopamine activity in the brain, in light of dopamine s role in reinforcement and nicotine s addictive properties. Nicotine increases dopamine turnover in the striatum and cerebral cortex (Clarke and Reuben 1996 Tani et al. 1997 Nanri et al. 1998). It also increases burst activity in dopamine neurons of the ventral tegmental area (VTA), a primary source of dopamine to the forebrain (Nisell et al. 1995 Fisher et al. 1998). Such a firing pattern in the VTA is associated with processes of reinforcement, learning, and cognitive activity. Nicotine actions on dopaminergic neurons occur at both somatodendritic sites and synaptic terminals. Further, both systemic nicotine and direct administration into the VTA increase dopamine release in the nucleus ac-... 

Bupropion is another alternative pharmacological approach to tobacco abstinence. It is an antidepressant drug that blocks reuptake of norepinephrine and dopamine, and also blocks nicotinic receptors in the low to intermediate micromolar range (Fryer and Lukas 1999). Thus, the effects of bupropion on nicotine addiction may be through dual effects on dopaminergic and nicotinic systems. Further, it has been an effective treatment in controlled studies, both alone and in combination with the nicotine patch. Bupropion alone or in combination with a nicotine patch was more effective than placebo or the nicotine patch alone. 

Smokers who have been abstinent for several weeks, or those who smoke for the first time, often experience nausea even at low blood nicotine concentrations. This aversive effect is due to the action of the drug on the chemoreceptor trigger zone whereby it indirectly activates the release of dopamine. Apomorphine and related dopamine agonists also cause nausea by activating the dopaminergic system in this brain region. 

Treatment for tobacco dependence involves a combination of behavioral therapies and pharmacological treatment. The most common pharmacological treatments involve nicotine repiacement therapy (NRT) and non-nicotine medications, including antidepressants. The antidepressant with the greatest weight of evidence for efficacy in the treatment of tobacco dependence is bupropion. The efficacy of bupropion for the treatment of tobacco dependence is attributed to the blockade of dopamine reuptake in the mesolimbic dopaminergic system. This area of the brain is believed to mediate reward for nicotine use and for other drug dependences. 

The nucleus accumbens is part of the limbic system. It receives dopaminergic input through the mesolimbic system that originates from cell bodies in the ventral segmental area (A 10 cell group). This mesolimbic dopaminergic pathway is part of the reward pathways. Drugs of abuse (cocaine, amphetamine, opiates or nicotine) have been shown to increase the level of dopamine release in these neurons. 

Owman, C., Fuxe, K., Jason, A., Kahrstrom, J., 1989. Studies of the protective actions of nicotine on neuronal and vascular functions in rats comparison between sympathetic noradrenergic and mesostriatal dopaminergic fiber system and the effect of a dopamine agonist. Prog. Brain Res. 79, 267-276. 

Abused drugs, including alcohol, opiates, cannabinoids, and psychostimulants, such as nicotine, activate the mesolimbic dopaminergic brain reward systems and increase dopamine levels in the nucleus accumbens. Specific CBl receptors modulate the... 

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