Role of nicotinic acetylcholine receptors in regulating dopamine neuron activity

Midbrain dopamine (DA) neurons play a central role in a wide range of behaviors, from attention and motivation to motor control and reinforcement. The release of DA is modulated by a number of factors, and its deregulation has been implicated in multiple psychiatric disorders, such as addiction. In particular, nicotinic acetylcholine receptors (nAChRs) are key modulators of DA cells. Nicotine, the main addictive component in tobacco, strongly interacts with these receptors in the midbrain DA systems, resulting in reinforcing effects that are at the core of tobacco addiction. nAChRs are virtually expressed on every cell of the DA system, both at pre-, post- and extra-synaptic locations. The complex issue of interpreting the role of the large portfolio of different nAChR subtypes expressed on ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) neurons, and especially their role in defining functional DAergic subpopulations, is far from being solved. In this review we will try to provide the reader with an integrative view of the nicotinic modulation of DA neurons and its influence at the cellular, systemic and behavioral levels (exploratory behavior), as well as its implication in the reinforcing effects of nicotine.