Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2High receptors

Abstract

Rationale Responsiveness to acute psychostimulant administration varies across ontogeny. Objective The purpose of the present study was to determine if age-dependent changes in D2High receptors may be responsible for the ontogeny of cocaine sensitivity in preweanling, adolescent, and adult rats. Methods [3H]-Domperidone/dopamine competition assays were used to determine ontogenetic changes in the proportion of D2High receptors in male and female preweanling [postnatal day (PD) 5, 10, 15, and 20], adolescent (PD 40), and adult rats (PD 80). 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 two days prior to testing. Distance traveled data were presented both untransformed and as percent of saline controls. Results Male and female preweanling rats (PD 5–PD 20) had a significantly greater percentage of dorsal striatal D2High 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. Conclusions Data from the present study are consistent with the hypothesis that ontogenetic changes in D2High receptors are responsible for age-dependent differences in psychostimulant sensitivity.

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

“…Ontogenetic changes in D2 receptors may be partially responsible for differences in psychostimulant sensitivity (McDougall et al 2015) since functionality of the D2 receptor continues to mature beyond the preweanling period (Der-Ghazarian et al 2014) and likely through adolescence. Other groups, assessing D2 density via autoradiography after early MPH exposure (PND 21) do not report enduring effects of the drug on either D1 or D2 density (Gill et al 2013).…”

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

“…Because of the potential translational relevance to young humans (Spear 2000; Andersen 2003), we compared rats from the preadolescent (PD 21–25) and adolescent (PD 41–45) periods (for a discussion of ontogenetic epochs, see Smith 2003; Frantz et al 2006). Based on previously cited adult ketamine studies, as well as ontogenetic data using psychostimulants (Becker et al 2001; Parylak et al 2008; McDougall et al 2015), it was hypothesized that adolescent female rats would show stronger unconditioned and conditioned locomotor activity than male rats. Preadolescent rats were also hypothesized to show robust ketamine-induced unconditioned and conditioned activity, but no sex differences were predicted in this prepubertal age group.…”

Importance of D1 and D2 receptor stimulation for the induction and expression of cocaine-induced behavioral sensitization in preweanling rats

“…In adult rats, for example, females are often hyperresponsive to an acute injection of cocaine [71,72], and show a more pronounced sensitized response than do male rats [73,74]. Prepubescent rats, on the other hand, do not typically exhibit sex differences in locomotion or sensitized responding after DA agonist treatment [75–80]. Consistent with these past studies, we found that cocaine did not differentially affect the locomotor activity of male and female preweanling rats on the pretreatment day, or cause sex-dependent differences in sensitized responding on the test day.…”