Ontogeny of the behavioral response to dopamine agonists after chronic cocaine

The behavioral response to separate and combined administration of dopamine D1 and D2 receptor agonists was assessed acutely and after chronic cocaine exposure (30 mg/kg s.c. b.i.d. for 5 days) in infant (PND11) and weanling (PND20) rats. In infants, quinpirole (quin) and SKF-38393 (SKF) elevated locomotion, mouthing and sniffing acutely. Rearing was increased and mouthing decreased by decreased by combined administration. In weanlings, quin increased by locomotion, mouthing and sniffing in weanlings, while SKF increased only mouthing. SKF inhibited quin-induced rearing and locomotion. Infants treated chronically with cocaine showed sensitized quin- and quin/SKF-induced locomotion and quin/SKF stimulated rearing and sniffing. In weanlings, locomotion was sensitized with all drug combinations, and rearing with SKF alone. These results indicate a developmental progression in the psychopharmacological response to dopamine receptor stimulation. While both D1 and D2 receptors are active in infants, the full complement of acute responses and complete capacity for sensitization develop later.