Intermittent access cocaine self-administration produces context-specific escalation and increased motivation

Abstract

The intermittent-access (IntA) self-administration procedure has been reported to produce intensified addiction-like behavior compared to continuous-access (ContA) procedures. In a common variation of the IntA procedure, cocaine is available for 5 min at the beginning of each half hour of a 6-h session. In contrast, during ContA procedures, cocaine is available continuously throughout a session, typically lasting one or more hours. Previous studies comparing procedures have used between-subjects designs, where separate groups of rats self-administer cocaine on either IntA or ContA procedures. The present study used a within-subjects design where subjects self-administered cocaine on the IntA procedure in one context and self-administered cocaine on the continuous short-access (ShA) procedure in another context during separate sessions. Across sessions, rats escalated cocaine intake in the IntA, but not ShA, context. Following sessions eight and 11, rats were administered a progressive ratio test in each context to monitor the change in cocaine motivation. Rats obtained more cocaine infusions on the progressive ratio test in the IntA context than in the ShA context following 11 sessions. These results suggest that addiction-like behaviors following IntA self-administration may be influenced by context-specific learning factors.

Keywords: Cocaine; Context; Intermittent-access; Learning; Self-administration; Short-access.

Figure 1.

Reinforcers Earned During Training. Mean (+/− SEM) reinforcers earned following acquisition training (“acq”) and per training session in each IntA or ShA context. **** indicates p < .0001, ** indicates p < .01

Figure 2.

Within-Session Reinforcers and Estimated Cocaine-Concentrations for IntA and ShA Contexts. (a) Mean (+/− SEM) reinforcers earned per minute within each availability component of the final IntA session. (b) Estimated whole-body cocaine concentration (mg/kg) for a representative rat chosen at random (“R8”) during the final IntA session. (c) Mean (+/− SEM) reinforcers earned per minute of the final ShA session. (d) Estimated whole-body cocaine concentration (mg/kg) for a representative rat chosen at random (“R8”) during the final ShA session.

Figure 3.

Progressive Ratio Test 1: Reinforcers, Breakpoints, and Total Responses. (a) Mean (+/− SEM) reinforcers earned and associated breakpoints (right y-axis) on the first set of progressive ratio testing between IntA and ShA conditions. Individual data for each subject indicated by connecting lines between points for each condition. (b) Mean (+/− SEM) total responses made on the first set of progressive ratio testing between IntA and ShA conditions.

Figure 4.

Progressive Ratio Test 2: Reinforcers, Breakpoints, and Total Responses. (a) Mean (+/− SEM) reinforcers earned and associated breakpoints (right y-axis) on the second set of progressive ratio testing between IntA and ShA conditions. Individual data for each subject indicated by connecting lines between points for each condition. (b) Mean (+/− SEM) total responses made on the second set of progressive ratio testing between IntA and ShA conditions. * indicates p < .05