Less is more: prolonged intermittent access cocaine self-administration produces incentive-sensitization and addiction-like behavior

Abstract

Rationale

Contemporary animal models of cocaine addiction focus on increasing the amount of drug consumption to produce addiction-like behavior. However, another critical factor is the temporal pattern of consumption, which in humans is characterized by intermittency, both within and between bouts of use.

Objective

To model this we combined prolonged access to cocaine (~70 days in total) with an intermittent access self-administration procedure (IntA), and used behavioral-economic indicators to quantify changes in motivation for cocaine.

Results

IntA produced escalation of intake, a progressive increase in cocaine demand (incentive-sensitization), and robust drug- and cue-induced reinstatement of drug-seeking behavior. We also asked whether rats that vary in their propensity to attribute incentive salience to reward cues (sign-trackers, STs vs. goal-trackers, GTs) vary in the development of addiction-like behavior. Although STs were more motivated to take cocaine after limited drug experience, after IntA, STs and GTs no longer differed on any measure of addiction-like behavior.

Conclusions

Exposure to large quantities of cocaine is not necessary for escalation of intake, incentive-sensitization or other addiction-like behaviors (IntA results in far less total cocaine consumption than ‘long access’ procedures). Also, the ST phenotype may increase susceptibility to addiction, not because STs are inherently susceptible to incentive-sensitization (perhaps all individuals are at risk), but because this phenotype promotes continued drug use, subjecting them to incentive-sensitization. Thus, the pharmacokinetics associated with the IntA procedure is especially effective in producing a number of addiction-like behaviors, may be valuable for studying associated neuroadaptations, and for assessing individual variation in vulnerability.