Changes in dopamine oxidation currents in the nucleus accumbens during unlimited-access self-administration of d-amphetamine by rats.

Abstract

In-vivo chronoamperometry in conjunction with stearate-modified carbon paste electrodes was used to monitor changes in dopamine (DA) oxidation currents in the nucleus accumbens during extended 24h and 48h sessions of i.v. self-administration of d-amphetamine (0.1mg/infusion) by rats. Animals in two control groups received "yoked" administration of d-amphetamine or saline vehicle. In a separate experiment, microdialysis with probes adjacent to the electrochemical electrodes was employed to estimate the sensitivity of these electrodes to different extracellular concentrations of DA reverse dialyzed at the probe surface in the presence of pharmacological blockade of the DA transporter. During unlimited access to d-amphetamine self-administration, several distinct changes in basal DA oxidation currents were observed: 1) a significant elevation that peaked after asymptotically equal to 4h; 2) a steady decline to values that were not significantly different from the values in the "yoked" vehicle group at asymptotically equal to 9h; 3) a further decline below control levels, reaching a nadir at asymptotically equal to 24h; 4) in the 48h session, a second phase of increased DA oxidation currents accompanied the reinstatement of a second bout of d-amphetamine self-administration, which followed an abstinence period. Examination of chronoamperometric records for individual rats, before, during and after the abstinence periods revealed 1) a significant reduction in basal DA oxidation currents in the self-administration group, relative to both "yoked" groups; 2) resumption of self-administration when DA currents were still attenuated; 3) an increase in DA currents following reinitiation of d-amphetamine self-administration. Comparison of changes in DA oxidation currents between groups revealed 1) significantly greater increases with self-administration vs "yoked" d-amphetamine administration; 2) a significant decrease in the self-administration vs the "yoked" d-amphetamine group during abstinence and 3) a circadian variation in the "yoked" vehicle group that was out of phase with the groups receiving the drug.