Less is more: prolonged intermittent access cocaine self administration produces incentive sensitization and addiction like behavior
RationaleContemporary 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.ObjectiveTo model this, we combined prolonged access to cocaine ~70 days in total) with an intermittent access (IntA) self administration procedure and used behavioral economic indicators to quantify changes in motivation for cocaine.ResultsIntA 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.ConclusionsExposure 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 are especially effective in producing a number of addiction like behaviors and may be valuable for studying associated neuroadaptations and for assessing individual variation in vulnerability.
Psychopharmacology