Chronic neonatal isolation stress enhances cocaine-induced increases in ventral striatal dopamine levels in rat pups.

Cocaine-induced increases in ventral striatal dopamine levels are enhanced in adult rats previously exposed to chronic stress. In neonatal rats, isolation from dam, nest, and siblings is stressful as evidenced by elevated corticosterone levels, an effect that increases with chronic isolation. Whether chronic neonatal isolation cross-sensitizes to cocaine leading to greater increases in ventral striatal dopamine levels was assessed in this study. Litters were assigned to isolate or non-handled conditions. After culling on postnatal Day 1 (PN1), pups in the neonatal isolation condition were isolated individually for 1 h/day on PN days 2-9 while pups in the non-handled condition were left undisturbed. On PN10, pups were implanted with probes aimed at the ventral striatum. Baseline measures of dopamine and its metabolite, DOPAC, were obtained. Separate groups of male and female pups were then administered 0, 2.5, 5.0, or 10 mg/kg cocaine and samples were collected for 2-h. Isolate pups showed greater cocaine-induced increases in ventral striatal dopamine levels than non-handled pups. However, DOPAC levels did not differ by isolation condition or gender. Neonatal isolation-induced increases in the effects of cocaine on ventral striatal dopamine levels are consistent with our previous study using amphetamine in 10-day-old pups and show that chronic stress sensitizes the dopamine response to psychostimulants in infant rats.