Developmental effects of prenatal cocaine exposure on 5-HT1A receptors in male and female rat offspring

Abstract

Prenatal cocaine exposure results in behavioral abnormalities throughout development in rats, but little is known regarding the biological mechanisms underlying these abnormalities. Pregnant rats received subcutaneous twice-daily injections (1 ml/kg) of normal saline or 15 mg/kg of cocaine hydrochloride throughout gestation (gestation days 1-20). Following delivery, pups were placed with untreated surrogates. Male and female pups were killed on postnatal days 30, 60 or 120 for assessment of 5-HT(1A) receptor development in the forebrain, diencephalon, midbrain and pons using radiolabel immunocytochemistry. Findings revealed gender and age differences in developmental regulation of 5-HT(1A) receptors, indicating that male rats are more susceptible to long-term consequences of prenatal cocaine exposure in comparison to females. This study also demonstrates gender-specific development of serotonin (5-HT(1A)) receptors across postnatal ages, demonstrating a fundamentally different pattern of development of 5-HT(1A) receptors between males and females.

Fig. 1

Gender differences throughout development. Males and females of both control and treatment groups display gender specific levels of 5-HT_1A receptors (5-HT_1A IB) at different ages (* p < 0.01). Males exhibited a peak of 5-HT_1A IB at PND 60, whereas females showed a steady decrease in IB, beginning at PND 30.

Fig. 2

Prenatal cocaine treatment significantly decreased 5-HT_1A expression (levels of 5-HT_1A IB) in 60- (c) and 120-day-old (e) males in the whole brain (forebrain, diencephalon, midbrain, and pons) compared to controls (* p < 0.01). Reduced 5-HT_1A expression is seen in females prenatally exposed to cocaine compared to control offspring at 30 days of age only (b), returning to control levels by 60 (d) and 120 days of age (f).