Basal extracellular dopamine is decreased in the rat nucleus accumbens during abstinence from chronic cocaine

Abstract

Rats were treated for 10 days with cocaine (20 mg/kg, i.p.) followed by either 1 or 10 days of abstinence. On the test day a microdialysis method was performed in which dopamine (DA) was added to the perfusate at concentrations above and below the expected extracellular concentration (0, 2.5, 5, and 10 nM) to generate a series of points that can be interpolated to determine the concentration of no net flux, which represents the extracellular DA concentration. The slope of the line generated by this method is the in vivo recovery of the dialysis probe. After 1 day of abstinence, there was no significant difference in basal DA levels in the nucleus accumbens (N ACC) between cocaine treated (4.1 ± 0.3 nM; mean ± SEM) and saline‐treated (3.9 ± 0.2 nM) groups. However, there was a significant increase in the slope of the cocaine‐treated group (0.91 ± 0.04 vs. 0.67 ± 0.08; P >0.03). After 10 days of abstinence, there were reduced basal extracellular levels of DA in the N ACC of the cocaine‐treated group as compared with saline‐treated controls (P <0.002). The basal extracellular DA concentration in the N ACC was 2.1 ± 0.3 nM for the cocaine group and 3.9 ± 0.2 nM for the control group. The slopes of the curves were not significantly different for the cocaine (0.63 ± 0.07) and saline (0.64 ± 0.09) groups. There was a significant interaction between cocaine and the length of abstinence with respect to the reduction in basal extracellular DA in the N ACC (P <0.0008) and also an interaction between cocaine and the length of abstinence with respect to the slope of the regression lines (P <0.03). The results suggest that both basal levels and the dynamics of extracellular DA in the N ACC are altered by chronic cocaine. These alterations may have relevance to the dopamine depletion hypothesis of cocaine addiction.