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

RATIONALE: Previously, we demonstrated that neonatal isolation increases acquisition of cocaine self-administration in adult male rats.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.