Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2(High) receptors

Responsiveness to acute psychostimulant administration varies across ontogeny. The purpose of the present study was to determine if age-dependent changes in D2(High) receptors may be responsible for the ontogeny of cocaine sensitivity in preweanling, adolescent, and adult rats. [(3)H]-Domperidone/dopamine competition assays were used to determine ontogenetic changes in the proportion of D2(High) receptors in male and female preweanling [postnatal day (PD) 5, 10, 15, and 20], adolescent (PD 40), and adult (PD 80) rats. In the behavioral experiment, responsiveness to cocaine (2.5, 5, 10, or 20 mg/kg) was assessed on PD 20, PD 40, and PD 80 for 60 min. Male and female rats were habituated to the apparatus on the 2 days prior to testing. Distance traveled data were presented both untransformed and as percent of saline controls. Male and female preweanling rats (PD 5-PD 20) had a significantly greater percentage of dorsal striatal D2(High) receptors than adolescent or adult rats. Likewise, preweanling rats (PD 20) were more sensitive to the behavioral effects of cocaine than the two older age groups. Adolescent and adult rats responded in a generally similar manner; however, analysis of the untransformed locomotor activity data suggested that adolescent rats were hyporesponsive to 2.5 and 20 mg/kg cocaine when compared to adults. Data from the present study are consistent with the hypothesis that ontogenetic changes in D2(High) receptors are responsible for age-dependent differences in psychostimulant sensitivity.