Within‐subject sensitization of striatal dopamine release after a single injection of cocaine: An in vivo microdialysis study

Abstract

Repeated microdialysis measurements, conducted 1 week apart at the same tissue site, were used to investigate the changes in basal and cocaine‐stimulated extracellular dopamine (DA) levels after a single prior exposure to either saline or cocaine. Dialysis probes were placed into rats previously implanted with guide cannulas and basal levels of dopamine (DA), and its metabolites (DOPAC and HVA) were estimated in 20‐min fractions of the dialysate. Basal levels in the extracellular fluid (ECF), estimated from pre‐implantation calibration of the probes, were 7.9 ± 0.7 nM DA, 4.9 ± 0.8 μM DOPAC, and 3.6 ± 0.6 μM HVA. After a stable baseline was obtained saline (1 ml/kg, i. p.) or cocaine (20 mg/kg, i. p.) was injected. Saline produced no significant changes in any of the neurochemical markers. A cocaine injection produced a sixfold increase in DA, while DOPAC and HVA were unchanged. One week later the same procedure was repeated except this time both groups received cocaine. In rats that had received cocaine 1 week earlier, basal DA levels in the ECF were doubled, whereas they were unchanged in rats that received saline a week earlier. Furthermore, the dopamine release in response to acute cocaine during the second week was elevated in animals which had been previously exposed to cocaine. Rotation was also measured during both weeks and, while a tendency toward behavioral sensetization was observed, it did not reach significance. Thus, a single exposure to cocaine, while not sufficient to induce behavioral sensitization in these rats, was sufficient to produce an elevated basal DA level and a sensitization of cocaine‐stimulated DA release when in vivo microdialysis measurements were repeated within the same rat. © Wiley‐Liss, Inc.