COMPARISON OF CHANGES IN EXTRACELLULAR DOPAMINE CONCENTRATIONS IN THENUCLEUS-ACCUMBENS DURING INTRAVENOUS SELF-ADMINISTRATION OF COCAINE OR D-AMPHETAMINE

Changes in extracellular concentrations of dopamine (DA) were measured in vivo in the nucleus accumbens of the rat during intravenous self-a dministration of either cocaine (0.25, 0.5, 1.0 mg/infusion) or d-amph etamine (0.05, 0.1, 0.2 mg/infusion). Drug intake was limited to 12 se lf-administered infusions per session for each drug/dose combination. Changes in extracellular DA concentrations were measured by two differ ent techniques: chronoamperometry in conjunction with chronically-impl anted stearate-modified carbon paste electrodes, or intracerebral micr odialysis with off-line analyses using high performance liquid chromat ography with electrochemical detection (HPLC-ED). Significant increase s in extracellular DA concentrations were observed with both in vivo t echniques during self-administration of each dose of cocaine or d-amph etamine. For each drug, the magnitude of change during the first hour of the test session was comparable across doses. However, the change o bserved over the first 2 h period, as measured by microdialysis and HP LC-ED, revealed a dose effect for cocaine, but no dose-response effect for d-amphetamine. The duration of the drug-induced elevation was inc reased significantly as a function of dose with both cocaine and d-amp hetamine. Data from the microdialysis experiments indicated that the h igh dose of d-amphetamine (0.2 mg/infusion) produced a significantly g reater increase in extracellular DA concentrations in the nucleus accu mbens than did the high dose of cocaine (1.0 mg/infusion), but that co mparable changes were induced by doses of 0.1 mg/infusion of d-ampheta mine and 1.0 mg/infusion of cocaine, respectively. Each dose of both p sychostimulant drugs also produced a significant decrease in dihydroxy phenylacetic acid (DOPAC) levels. The latter finding indicated that th e electrochemical signal measured in these studies was not due to the oxidation of DOPAC. These results confirm that self-administration of cocaine or d-amphetamine by the rat is accompanied by a significant in crease in extracellular DA concentrations in the nucleus accumbens. Th e fact that two different psychomotor stimulant drugs of abuse have qu alitatively similar neurochemical correlates when self-administered, a dds credence to the hypothesis that their reinforcing properties are r elated to dynamic changes in DA concentrations in the ventral striatal region of the brain.