Parametric analysis of the effects of cocaine and cocaine pretreatment on dopamine release in the nucleus accumbens measured by fast cyclic voltammetry.

Fast cyclic voltammetry was used to measure dopamine (DA) release in the nucleus accumbens of anaesthetized rats, in response to electrical sine-wave stimulation of the ventral tegmental area. Voltammetric signals followed increases in either frequency (50-100 Hz), intensity (50-100 microA) or duration (0.5-5.0 s) of the stimulus. Cocaine administration (10 mg/kg) preferentially increased DA release by weak electrical stimuli. Cocaine pretreatment (3 x 10 mg/kg, two weeks earlier) preferentially increased DA release by stronger stimuli, and the effects of acute cocaine were potentiated in these animals. The effects of increasing stimulus duration conformed to first order kinetics. Cocaine pretreatment selectively increased the kinetic parameter representing maximal release, while acute cocaine administration preferentially decreased the parameter representing the stimulus duration eliciting half maximal release. The lack of statistical interaction between these two effects suggests that sensitization of the response to acute cocaine by cocaine pretreatment may simply reflect an increase in the size of the releasable pool of DA.