PROTECTIVE EFFECTS OF MATERNAL BUSPIRONE TREATMENT ON SEROTONIN REUPTAKE SITES IN ETHANOL-EXPOSED OFFSPRING

Previous work in this laboratory demonstrated that in utero ethanol ex posure is associated with abnormal development of the serotonergic sys tem. Specific abnormalities included deficiencies of serotonin (5-HT) and its metabolites, and cortical 5-HT reuptake sites. The concentrati on of 5-HT1A receptors was also altered. The serotonin deficit was det ected in the fetal ethanol-exposed brain, at an age when 5-HT would no rmally function as an essential trophic factor. Thus, it was hypothesi zed that the early 5-HT ethanol-associated deficit of an essential tro phic factor (e.g. 5-HT) could contribute to subsequent developmental a bnormalities in serotonergic neurons. In the present investigation we used quantitative autoradiography (QAR) to more fully characterize the developmental abnormalities in 5-HT reuptake sites in developing offs pring of ethanol-fed rats. In addition, we attempted to overcome the p otential negative impact of the ethanol-associated deficit of fetal 5- HT, by administering a 5-HT1A agonist, buspirone, to pregnant rats. Th ese investigations demonstrated that postnatal (PN) 19 and/or 35 day e thanol-exposed offspring had a significant decrease in [H-3]citalopram binding to 5-HT reuptake sites in the frontal cortex, parietal cortex , lateral hypothalamus, substantia nigra, medial septum, and striatum. In contrast, [H-3]citalopram binding was increased in the dorsal raph e on PN5 and in the median raphe on PN19. No significant ethanol-assoc iated changes were detected in the hippocampus CA3 region or in the am ygdala. When [H-3]citalopram binding was compared in the offspring of saline- and buspirone-treated dams, it appeared that maternal treatmen t with buspirone prevented or reversed most of the ethanol-associated developmental abnormalities in 5-HT reuptake sites. Buspirone prevente d the decline in binding of [H-3]citalopram in the frontal cortex, lat eral hypothalamus, substantia nigra and medial septum. Similarly, busp irone treatment prevented the ethanol-associated increase in binding i n the dorsal and median raphe. Additional experiments are needed to el ucidate the impact of maternal buspirone treatment on the development of other neurotransmitter systems in offspring.