Role of alpha6 nicotinic receptors in CNS dopaminergic function: relevance to addiction and neurological disorders.

摘要

Although a relative newcomer to the nicotinic acetylcholine receptor (nAChR) family, substantial evidence suggests that alpha6 containing nAChRs play a key role in CNS function. This subtype is unique in its relatively restricted localization to the visual system and catecholaminergic pathways. These latter include the mesolimbic and nigrostriatal dopaminergic systems, which may account for the involvement of alpha6 containing nAChRs in the rewarding properties of nicotine and in movement. Here, we review the literature on the role of alpha6 containing nAChRs with a focus on the striatum and nucleus accumbens. This includes molecular, electrophysiological and behavioral studies in control and lesioned animal models, as well as in different genetic models. Converging evidence suggest that the major alpha6 containing nAChRs subtypes in the nigrostriatal and mesolimbic dopamine system are the alpha6beta2beta3 and alpha6alpha4beta2beta3 nAChR populations. They appear to have a dominant role in regulating dopamine release, with consequent effects on nAChR-modulated dopaminergic functions such as reinforcement and motor behavior. Altogether these data suggest that drugs directed to alpha6 containing nAChRs may be of benefit for the treatment of addiction and for neurological disorders with locomotor deficits such as Parkinson's disease.