Neonatal isolation enhances maintenance but not reinstatement of cocaine self-administration in adult male rats.

Abstract

Previously, we demonstrated that neonatal isolation increases acquisition of cocaine self-administration in adult male rats. Now we examine whether neonatal isolation enhances maintenance and cocaine-induced reinstatement of extinguished self-administration behavior. To test the specificity of the effect, a separate study examined maintenance of food responding. Litters were subjected to neonatal isolation (individual isolation; 1 h/day; postnatal days 2-9) or were non-handled. In experiment 1, adult male rats trained to self-administer cocaine (0.5 mg/kg per infusion; fixed-ratio 3 or FR3) were tested under fixed and progressive ratio (PR) schedules with different cocaine doses (0.125-1.0 mg/kg per infusion). After cocaine self-administration was extinguished, cocaine (0.5 or 2 mg/kg)-induced reinstatement of responding was assessed. In experiment 2, responding for food under an FR15 and two PR schedules were assessed in separate groups of neonatally isolated and non-handled male rats. Neonatally isolated rats responded for low cocaine doses at higher rates and infused more cocaine relative to non-handled rats under both FR and PR schedules. However, there are no group differences in cocaine-induced reinstatement or in responding for food under the PR schedules. However, neonatally isolated rats lever pressed for food at lower rates under the FR schedule. Together with our previous studies, the results of the present study suggest that the early life stress of neonatal isolation enhances cocaine-taking (acquisition and maintenance) at lower doses but does not alter drug-induced cocaine-seeking (reinstatement) behavior.