Ontogenetic differences in the psychopharmacological responses to separate and combined stimulation of D1 and D2 dopamine receptors during the neonatal to weanling age period

Abstract

The psychopharmacological responses to separate and combined stimulation of dopamine D1 and D2 receptors were examined in neonatal (postnatal day 3-4, P3-4), infant (P10-11) and weanling (P21-22) rat pups. Thirty minutes prior to testing rat pups received a subcutaneous (SC) injection of saline, 1.0 (P3-4, P10-11) or 0.5 (P21-22) mg/kg of the D2 agonist quinpirole. Fifteen minutes later all animals received an additional SC injection of 0, 0.01, 0.1, 1.0 or 10.0 mg/kg of the D1 agonist SKF-38393. Pups were tested for 5 min via a time-sampling procedure in a humidity controlled incubator for 3- and 10-day-old animals and in a divided glass aquarium for 21-day-old pups. Although administration of either agonist alone induced increases in forward locomotion and/or sniffing behavior at all test ages, the adult-typical grooming response to SKF-38393 and increase in vertical movements in response to quinpirole were not evident until weaning. Similarly, although combined administration of the agonists induced synergistic responding at each test age, only weanlings exhibited an adult-typical synergistic increase in licking. Thus, although the D1 and D2 receptor subtypes appear to be functionally present and coupled in some fashion throughout the neonatal to weanling age period, ontogenetic differences are evident in the behavioral responses elicited by separate and combined stimulation of these receptor subtypes.