Effects of cocaine context on NAcc dopamine and behavioral activity after repeated intravenous cocaine administration

Abstract

In two conditioning experiments, identical procedures (previously shown to produce place preferences for a cocaine-paired environment) were used to assess dopaminergic and behavioral activity correlates of cocaine reward conditioning and sensitization. In these experiments, animals received repeated injections of intravenous cocaine (4.2 mg/kg×6) or saline (0.2 ml×6) on alternating days. One group in each of these experiments (‘Cocaine Cues’) occupied a consistent distinctive environment during cocaine treatments and testing sessions. For the other conditioned group (‘Novel’), all procedures were the same, except that the last cocaine injection was administered while animals were occupying a novel environment. During day 1 and day 6 of the cocaine treatment, behavioral activity was assessed in experiment 1 and in vivo microdialysis procedures were conducted in experiment 2. Over the course of the conditioning sessions, cocaine-induced behavioral activity (locomotion and rearing) increased significantly in the Cocaine Cues group, but not in the Novel group. In addition, cocaine-induced increases in NAcc dopamine levels were significantly greater when cocaine-experienced animals were tested in a cocaine-paired environment compared to equally experienced and cocaine-naive animals tested in a novel environment. Context-dependent behavioral sensitization is a well-documented phenomenon. The observation of a corresponding enhancement of dopamine efflux in lieu of a lengthy withdrawal period is uncommon, but can be attributed to methodological differences across studies. The present study uniquely demonstrates concurrent context-dependent potentiation of behavioral and dopaminergic responses to cocaine occurring in conjunction with cocaine reward.