Neuronal nicotinic acetylcholine receptors in reward and addiction

Abstract

Drugs of abuse stimulate the pleasure centers of the brain to initiate addiction. During the beginning stages of addiction, the rewarding or reinforcing properties of abused drugs drive intake. However, as addiction develops drug intake is more likely to be dominated by negative reinforcement. The main reward center of the brain is the mesolimbic pathway which consists of dopaminergic neurons originating in the ventral tegmental area that project to the nucleus accumbens. Most, if not all, abused drugs stimulate this circuit resulting in increased release of the neurotransmitter, dopamine, in the nucleus accumbens, a phenomenon intimately associated with reward and reinforcement. Neuronal nAChRs are robustly expressed within the microcircuitry of this reward pathway. Drugs of abuse such as nicotine and alcohol directly interact with nAChRs expressed within the mesolimbic circuit to affect drug reward sensitivity, whereas with other drugs of abuse such as the psychostimulants and opioids, nAChRs play a more indirect, modulatory role on drug reward. In this chapter, the expression and function of nAChRs in the reinforcing/rewarding properties of drugs of abuse are explored.