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Prenatal Alcohol Exposure Results in Long‐Term Serotonin Neuron Deficits in Female Rats: Modulatory Role of Ovarian Steroids
Author(s) -
Sliwowska Joanna H.,
Song Hyun Jung,
Bodnar Tamara,
Weinberg Joanne
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12224
Subject(s) - medicine , endocrinology , dorsal raphe nucleus , ovariectomized rat , serotonin , brainstem , estrogen , serotonergic , receptor
Background Previous studies on male rodents found that prenatal alcohol exposure ( PAE ) decreases the number of serotonin immunoreactive (5‐ HT ‐ir) neurons in the brainstem. However, data on the effects of PAE in females are lacking. In light of known sex differences in responsiveness of the 5‐HT system and known effects of estrogen ( E 2 ) and progesterone ( P 4 ) in the brain, we hypothesized that sex steroids will modulate the adverse effects of PAE on 5‐ HT neurons in adult females. Methods Adult females from 3 prenatal groups (Prenatal alcohol‐exposed [ PAE ], Pair‐fed [ PF ], and ad libitum‐fed Controls [ C ]) were ovariectomized ( OVX ), with or without hormone replacement, or underwent Sham OVX . 5‐ HT ‐ir cells were examined in key brainstem areas. Results Our data support the hypothesis that PAE has long‐term effects on the 5‐HT system of females and that ovarian steroids have a modulatory role in these effects. Intact ( S ham OVX ) PAE females had marginally lower numbers of 5‐ HT ‐ir neurons in the dorsal raphe nucleus of the brainstem compared with PF and C females. This marginal difference became significant following removal of hormones by OVX . Replacement with E 2 restored the number of 5‐ HT ‐ir neurons in PAE females to control levels, while P 4 reversed the effects of E 2 . Importantly, despite these differential responses of the 5‐HT system to ovarian steroids, there were no differences in E 2 and P 4 levels among prenatal treatment groups. Conclusions These data demonstrate long‐term, adverse effects of PAE on the 5‐HT system of females, as well as differential sensitivity of PAE compared with control females to the modulatory effects of ovarian steroids on 5‐HT neurons. Our findings have important implications for understanding sex differences in 5‐HT dysfunction in depression/anxiety disorders and the higher rates of these mental health problems in individuals with fetal alcohol spectrum disorder.