Effects of cocaine self-administration history under limited and extended access conditions on in vivo striatal dopamine neurochemistry and acoustic startle in rhesus monkeys

Abstract

The transition from infrequent and controlled cocaine use to dependence may involve enduring changes in neurobiology as a consequence of persistent drug use. The present study utilized an intravenous drug self-administration protocol of increasing cocaine access to evaluate potential changes in dopamine function in vivo, including changes in sensitivity to psychostimulants. Drug-naïve rhesus monkeys were provided limited access (1 h) to cocaine self-administration for 60 days followed by 60 days under an extended access condition (4 h). Basal levels of striatal extracellular dopamine and its metabolites, as well as the effectiveness of cocaine and amphetamine to elevate dopamine, were determined with in vivo microdialysis before the initiation of cocaine self-administration and during limited and extended access. The effect of cocaine and amphetamine on the acoustic startle response was also examined to assess complementary behavioral changes as a function of drug history. Extended access to cocaine self-administration lead to increased daily intake compared to limited access conditions but did not result in escalated intake over time. However, cocaine- and amphetamine-induced increases in striatal dopamine were diminished as a function of cocaine self-administration history. Surprisingly, there was no effect of drug-taking history on sensitivity to psychostimulant-induced enhancement of startle amplitude. The present experiments provide evidence of a hypofunctional dopamine system that is not associated with an escalation in drug intake or reflected in measures of acoustic startle.