Neonatal exposure to oestradiol increases dopaminergic transmission in nucleus accumbens and morphine-induced conditioned place preference in adult female rats.

Steroid sex hormones produce physiological effects in reproductive tissues and also in nonreproductive tissues, such as the brain, particularly in cortical, limbic and midbrain areas. Dopamine (DA) neurones involved in processes such as prolactin secretion (tuberoinfundibular system), motor circuit regulation (nigrostriatal system) and driving of motivated behaviour (mesocorticolimbic system) are specially regulated by sex hormones. Indeed, sex hormones promote neurochemical and behavioural effects induced by drugs of abuse by tuning midbrain DA neurones in adult animals. However, the long-term effects induced by neonatal exposure to sex hormones on dopaminergic neurotransmission have not been fully studied. The present study aimed to determine whether a single neonatal exposure with oestradiol valerate (EV) results in a programming of dopaminergic neurotransmission in the nucleus accumbens (NAcc) of adult female rats. To answer this question, electrophysiological, neurochemical, cellular, molecular and behavioural techniques were used. The data show that frequency but not amplitude of the spontaneous excitatory postsynaptic current is significantly increased in NAcc medium spiny neurones of EV-treated rats. In addition, DA content and release are both increased in the NAcc of EV-treated rats, caused by an increased synthesis of this neurotransmitter. These results are functionally associated with a higher percentage of EV-treated rats conditioned to morphine, a drug of abuse, compared to controls. In conclusion, neonatal programming with oestradiol increases NAcc dopaminergic neurotransmission in adulthood, which may be associated with increased reinforcing effects of drugs of abuse.

Neonatal exposure to estradiol valerate reprograms the rat ovary androgen receptor and anti-Müllerian hormone to a polycystic ovary phenotype.

To understand the impact of exposure to steroids in the early step of ovary development (a stage occurring in uterus in humans), we studied neonatal exposure to estradiol valerate (EV) in rats regarding polycystic ovary (PCO) development as well as expression of androgen receptor (Ar) and anti-Müllerian hormone (AMH), a marker of ovarian follicular development. Rats exposed to one dose of EV (10mg/kg, sc) during their first 12h of life were euthanized at 2, 30 and 60days of age. Gene array and real-time PCR studies showed Ar and AMH up regulation in the ovary at 2days of age and persisted at 60days of age, when a PCO phenotype was evident with increased levels of Ar and AMH proteins. The single neonatal exposure in rats suggests participation of EV in developing PCO syndrome. Its persistence also suggests that estradiol reprograms ovarian function and disease during adulthood.