Sex mediates dopamine and adrenergic receptor expression in adult rats exposed prenatally to cocaine

Abstract

The extent of catecholaminergic receptor and respective behavioral alterations associated with prenatal cocaine exposure varies according to exogenous factors such as the amount, frequency, and route of maternal exposure, as well as endogenous factors such as specific brain regions under consideration and sex of the species. The goal of the current study was to use autoradiography to delineate possible moderators of dopaminergic and adrenergic receptor expression in adult rat offspring exposed to cocaine in utero. The current study demonstrated sex-dependent D1 receptor, alpha2, and noradrenergic transporter binding alterations in prelimbic, hippocampus, and anterior cingulate regions of adult rat brains exposed to cocaine during gestational days 8-21. Of further interest was the lack of alterations in the nucleus accumbens for nearly all receptors/transporters investigated, as well as the lack of alterations in D3 receptor binding in nearly all of the regions investigated (nucleus accumbens, prelimbic region, hippocampus, and cingulate gyrus). Thus, the current investigation demonstrated persistent receptor and transporter alterations that extend well into adulthood as a result of cocaine exposure in utero. Furthermore, the demonstration that sex played a mediating role in prenatal cocaine-induced, aberrant receptor/transporter expression is of primary importance for future studies that seek to control for sex in either design or analysis.

Figure 1. Saline Baselines

Specific binding (fmol/mg) for D1 receptors (A), D3 receptors (B), α2 adrenergic receptors (C), and NET (D) in the saline control group. There was a main effect of region for each receptor, however, no main effects of sex or Sex × Region interactions were present for any receptors and regions investigated.

Figure 2. SCH23390 and 7-OH-PIPAT (D1 and D3 receptors)

Change scores for males and females relative to saline baseline (fmol/mg) for SCH23390 and 7-OH-PIPAT (D1 and D3 receptors) in the prelimbic region (A), CG1 (B), and NAcc shell (C) for both 1/day and 2/day cocaine groups. For D1 receptors, main effect of sex only present when collapsing treatment groups. For D3 receptors, # = Sex × Treatment interaction.

Figure 3. Paraiodoclonidine (α2 receptors)

Change scores for males and females relative to saline baseline (fmol/mg) for Paraiodoclonidine (α2 receptors) in the prelimbic region (A), CG1 (B), CG2 (C), CA1 (D), and CA2 (E) for both 1/day and 2/day cocaine groups. * = p < .01, ** = p < .001 *** = p < .0001.

Figure 4. Nisoxetine (NET)

Change scores for males and females relative to saline baseline (fmol/mg) for Nisoxetine (NET binding) in the prelimbic region for both 1/day and 2/day cocaine groups. 2 × 2 ANOVA indicated a significant main effect of sex. * = p < .01