Acquisition of cocaine self-administration after social stress: role of accumbens dopamine

Abstract

Exposure to either aversive or rewarding environmental stimuli increases extracellular dopamine (DA) concentrations in terminal areas of the mesocorticolimbic dopamine system. Furthermore, behavioral reactivity to an environmental stressor has been shown to correlate with latency to initiate self-administration of psychomotor stimulant drugs. The present study examined the behavioral and dopaminergic responses of rats to social defeat stress and compared latencies to initiate cocaine self-administration in defeated and non-defeated rats. In vivo microdialysis was used to examine the effects of social defeat stress on DA concentrations in nucleus accumbens of freely-moving rats. During the experimental session, dialysate and video recording samples were collected from previously-defeated and non-defeated “intruder” rats in consecutive phases, while (1) in the home cage, (2) when placed in the empty, soiled cage of a resident rat which had previously defeated them, and (3) when exposed to threat of defeat by the resident. Immediately following threat of defeat, previously-defeated and non-defeated intruders were given the opportunity to self-administer cocaine IV. When exposed to the olfactory cues of an aggressive resident, extracellular DA levels in nucleus accumbens increased to approximately 135% of baseline in previously defeated rats versus 125% of baseline in non-defeated rats. When exposed to social threat by the resident, DA levels further increased to 145% of baseline in previously defeated rats versus 120% in non-defeated rats. Previously defeated rats acquired cocaine self-administration in approximately half the time of non-defeated rats, consistent with the hypothesis that prior stress exposure may induce a cross-sensitization to the rewarding effects of cocaine. These results are consistent with the idea that exposure to stress may induce changes in central dopaminergic activity, which may render an individual more vulnerable to acquiring psychomotor stimulant self-administration.