The influence of reinforcing effects of cocaine on cocaine-induced increases in extinguished responding in cynomolgus monkeys

Abstract

Rationale: Although reinstatement of extinguished cocaine self-administration is widely used as an animal model of relapse, it is unclear which behavioral effects of the drug stimulus (i.e., unconditioned, discriminative or reinforcing) mediate the increases in responding after extinction.

Objective: To examine the influence of experience with cocaine as a reinforcer on the ability of response-independent cocaine injections to increase extinguished responding.

Materials and methods: Effects of noncontingent injections of cocaine (0.01-1.0 mg/kg, i.v.) were assessed in two groups of cynomolgus monkeys, those with extensive histories of cocaine self-administration when responding was maintained under a concurrent fixed ratio (FR) 50 schedule of saline and food presentation (n = 8) and cocaine-naive monkeys (n = 5) responding under an FR 50 schedule of food presentation. In the latter group, the effects of noncontingent cocaine and food (one or five pellets) were examined before and after a brief history of cocaine (0.03 mg/kg/inj) self-administration under an FR 50 schedule.

Results: In the cocaine-experienced subjects responding under a concurrent schedule of saline and food availability, noncontingent cocaine dose-dependently increased injection-lever responding. In the initially cocaine-naive subjects, no dose of cocaine increased extinguished food-maintained responding before or after a brief exposure to cocaine self-administration. In contrast, noncontingent delivery of five food pellets significantly increased extinguished food-maintained responding after cocaine self-administration.

Conclusions: These results support the view that, under self-administration conditions, the discriminative stimulus effects of cocaine play a prominent role in the ability of cocaine to increase extinguished responding.

Figure 1

Effects of noncontingent injections of cocaine (0.01-0.56 mg/kg) on response distribution under a concurrent schedule of saline and food presentation in monkeys with extensive cocaine self-administration histories. Ordinate, percent of total responses emitted on the injection lever, Abscissa, dose of noncontingent cocaine injection. Point above “S” represent response distribution when saline was the alternative to food. Data are expressed as mean ± SEM. *, significant difference from response distribution in the absence of the response-independent cocaine (p<0.05).

Figure 2

Effects of noncontingent cocaine or food on the number of fixed ratios completed during extinction before (open symbols) and after (closed symbols) a brief history of cocaine self-administration. Points above EXT are the mean (± SEM) data from last three extinction sessions. *, significantly different from EXT conditions (p<0.05).