Cue-induced reinstatement of cocaine seeking in the rat "conflict model": effect of prolonged home-cage confinement

Abstract

Rationale and objectives: Drug addiction is not just the repeated administration of drugs, but compulsive drug use maintained despite the accumulation of adverse consequences for the user. In an attempt to introduce adverse consequences of drug seeking to laboratory animals, we have developed the "conflict model," in which the access of rats to a reinforcing lever allowing self-administration requires passing of an electrified grid floor. In this model, the current intensity leading to complete abstinence from drug seeking can be measured individually. The present study was designed to evaluated whether reinstatement of drug or natural reward seeking, despite the presence of the electrical barrier, can be achieved by presentation of discrete cues that were associated with the reward, and whether prolonged home-cage confinement can facilitate such reinstatement in this model.

Methods: The "conflict model" was used to test cue-induced reinstatement in the presence of the electrical barrier, after 1 or 14 days of home-cage confinement, in groups of rats that were previously trained to self-administer cocaine or sucrose.

Results: Although similar shock intensity was required to suppress sucrose or cocaine self-administration, subjects exhibited significantly lower response to sucrose-associated as compared to cocaine-associated cues, during the reinstatement test. Importantly, cue-induced reinstatement of cocaine seeking was attenuated following 14 days of home-cage confinement.

Conclusions: The incorporation of aversive consequence in the self-administration model enable detection of what can be interpreted as a compulsive component unique to drug reinforcers. Moreover, the effect of the aversive consequence seems to increase following home-cage confinement.

Fig 1. Experimental design utilizing the ‘conflict’ model procedure

A procedure designed to model reinforced drug seeking under adverse consequences, abstinence induced and maintained by adverse consequences (even though seeking would still procure the drug), and cue-induced reinstatement in face of adverse consequences.

Fig 2. Individual performance of cocaine and sucrose SA groups during the reinstatement test

The number of previously active (black bars) and inactive (white bars) lever responses during reinstatement tests are presented for each individual rat from each of the indicated groups. The diamond shapes present the individual AT of each rat. Panels a and b present reinstatement to cocaine seeking under the AT condition; panels c and d present reinstatement to cocaine seeking under the 0.85AT condition, and panels e and f present reinstatement to sucrose seeking under the 0.85AT condition.

Fig 3. Group rates of cue-induced reinstatement behavior

Panel a presents the total cue-reinstatement rate for the groups tested after 1d (black bars) and 14d (white bars) of home-cage confinement. Panel b present the mean ± SEM number of previously active lever responses during the cue-induced reinstatement test, for the groups tested after 1d (black bars) and 14d (white bars) of home-cage confinement (*p<0.05).

Fig 4. Cocaine or sucrose seeking behavior during the no-shock reinstatement test

The mean ± SEM number of lever presses on the previously active (black bars) and inactive (white bars) levers during the ‘free access’ (no shock) reinstatement test is presented for the various cocaine or sucrose groups that were previously tested under the 0.85AT condition.