Effects of stress and aversion on dopamine neurons: implications for addiction.

Stress plays a key role in modulating the development and expression of addictive behavior, and is a major cause of relapse following periods of abstinence. In this review we focus our attention on recent advances made in understanding how stress, aversive events, and drugs of abuse, cocaine in particular, interact directly with dopamine neurons in the ventral tegmental area, and how these interactions may be involved in stress-induced relapse. We start by outlining how dopamine neurons respond to aversive stimuli and stress, particularly in terms of firing activity and modulation of excitatory synaptic inputs. We then discuss some of the cellular mechanisms underlying the effects of cocaine on dopamine neurons, again with a selective focus on synaptic plasticity. Finally, we examine how the effects of stress and cocaine interact and how these cellular mechanisms in ventral tegmental area dopamine neurons may be engaged in stress-induced relapse.