Prenatal Alcohol Exposure Results in Long-Term Serotonin Neuron Deficits in Female Rats: Modulatory Role of Ovarian Steroids
Version of Record online: 5 AUG 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 38, Issue 1, pages 152–160, January 2014
How to Cite
Sliwowska, J. H., Song, H. J., Bodnar, T. and Weinberg, J. (2014), Prenatal Alcohol Exposure Results in Long-Term Serotonin Neuron Deficits in Female Rats: Modulatory Role of Ovarian Steroids. Alcoholism: Clinical and Experimental Research, 38: 152–160. doi: 10.1111/acer.12224
- Issue online: 21 JAN 2014
- Version of Record online: 5 AUG 2013
- Manuscript Accepted: 29 APR 2013
- Manuscript Received: 7 FEB 2013
- Canadian Institutes for Health Research STIHR
- Prenatal Alcohol Exposure;
- Serotonin (5-HT);
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 (E2) and progesterone (P4) in the brain, we hypothesized that sex steroids will modulate the adverse effects of PAE on 5-HT neurons in adult females.
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.
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 (Sham 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 E2 restored the number of 5-HT-ir neurons in PAE females to control levels, while P4 reversed the effects of E2. Importantly, despite these differential responses of the 5-HT system to ovarian steroids, there were no differences in E2 and P4 levels among prenatal treatment groups.
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.