Behavioral responses to dopamine agonists in adult rats exposed to cocaine during the preweaning period.

In order to determine whether developmental cocaine exposure altered the functional responses of dopamine systems, the behavioral responses to selective D1 or D2/D3 agonists were examined and compared to rats treated during the same period with a selective inhibitor of the dopamine transporter, GBR 12909. Sprague-Dawley rats were administered cocaine or GBR 12909 at 25 or 50 mg/kg/day during postnatal days (PND) 11-20. At 60+ days of age, rats were administered a challenge drug (either SKF 82958, a full D1 agonist, at 1.0 or 10 mg/kg, or quinpirole, a D2/D3 agonist, at 0.08 or 0.5 mg/kg, or saline) and subjected to 1 h of behavioral assessment. The cocaine or GBR treatments produced significant effects in three behavioral categories: distance traveled, sniffing, and rearing. For distance traveled, preweaning treatments interacted with sex since in the males, all cocaine- and GBR-treated groups showed relatively flat patterns of locomotor activity across time blocks, while in the treated females, locomotor activity typically increased across the time blocks. For other behaviors, the treatments generally produced enhanced responses to the challenge drugs. These results suggest that intermittent inhibition of the dopamine transporter with either cocaine or GBR during PND 11-20 produces long-term alterations in the functional responses of dopaminergic systems but that the neural substrates for these effects depend upon the sex of the animal.