Behavioral responses to a D1 dopamine agonist in weanling rats treated neonatally with cocaine and delta9-tetrahydrocannabinol.

We determined whether neonatal exposure to cocaine with or without delta9-tetrahydrocannabinol (THC) altered the behavioral responses of weanling rats to the full D1 dopamine (DA) agonist SKF 81297. Rats were injected SC once daily from postnatal day (PD) 1 through 5 with cocaine (20 mg/kg), the same dose of cocaine plus THC (10 mg/kg), or drug vehicle. On PDs 24, 25, or 26, male and female littermates were administered 3 or 10 mg/kg of SKF 81297 or saline vehicle, and then tested 15 min later in an open-field apparatus. Neither neonatal drug treatment nor gender influenced the behavioral responses to SKF 81297. The drug challenge did, however, produce several dose-dependent behavioral effects, including increases in locomotor activity, line crossing, sniffing, and headshakes, and a decreased incidence of rearing, grooming, and stationary behavior. Furthermore, even though earlier administration of cocaine and THC failed to alter D1 receptor sensitivity, animals in both neonatal treatment groups exhibited an overall increase in grooming behavior and a decrease in sniffing compared to controls when the results were combined across doses of SKF 81297. These findings indicate that early postnatal exposure to cocaine can alter certain behaviors independently of functional changes in the D1 receptor system.