Abstinence from chronic cocaine self-administration alters striatal dopamine systems in rhesus monkeys

Abstract

Although dysregulation within the dopamine (DA) system is a hallmark feature of chronic cocaine exposure, the question of whether these alterations persist into abstinence remains largely unanswered. Nonhuman primates represent an ideal model in which to assess the effects of abstinence on the DA system following chronic cocaine exposure. In this study, male rhesus monkeys self-administered cocaine (0.3 mg/kg per injection, 30 reinforcers per session) under a fixed-interval 3-min schedule for 100 days followed by either 30 or 90 days abstinence. This duration of cocaine self-administration has been previously shown to decrease DA D2-like receptor densities and increase levels of D1-like receptors and DA transporters (DAT). Responding by control monkeys was maintained by food presentation under an identical protocol and the same abstinence periods. [(3)H]SCH 23390 binding to DA D1 receptors following 30 days of abstinence was significantly higher in all portions of the striatum, compared to control animals, whereas [(3)H]raclopride binding to DA D2 receptors was not different between groups. [(3)H]WIN 35 428 binding to DAT was also significantly higher throughout virtually all portions of the dorsal and ventral striatum following 30 days of abstinence. Following 90 days of abstinence, however, levels of DA D1 receptors and DAT were not different from control values. Although these results indicate that there is eventual recovery of the separate elements of the DA system, they also highlight the dynamic nature of these components during the initial phases of abstinence from chronic cocaine self-administration.

Figure 1

Representative autoradiograms of [³H] SCH 23390 binding to D1 receptors (top panel) and [³H]WIN 35428 binding to dopamine transporters (bottom panel) in coronal sections of rhesus monkey striatum. (a, d) Control animal responding for food reinforcement. (b, e) Cocaine self-administration animal with 30 days abstinence. (c, f) Cocaine self-administration animal with 90 days abstinence.

Figure 2

Binding densities of D1 receptors for individual animals averaged across the entire striatum following either food reinforcement (controls), or 30 or 90 days abstinence from chronic cocaine self-administration. Means for groups are depicted with black bars, ***p < 0.001 compared to food-reinforced controls.