Protective effects of maternal buspirone treatment on serotonin reuptake sites in ethanol-exposed offspring.
Previous work in this laboratory demonstrated that in utero ethanol exposure is associated with abnormal development of the serotonergic system. Specific abnormalities included deficiencies of serotonin (5-HT) and its metabolites, and cortical 5-HT reuptake sites. The concentration of 5-HT1A receptors was also altered. The serotonin deficit was detected in the fetal ethanol-exposed brain, at an age when 5-HT would normally function as an essential trophic factor. Thus, it was hypothesized that the early 5-HT ethanol-associated deficit of an essential trophic factor (e.g. 5-HT) could contribute to subsequent developmental abnormalities 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 offspring of ethanol-fed rats. In addition, we attempted to overcome the potential negative impact of the ethanol-associated deficit of fetal 5-HT, by administering a 5-HT1A agonist, buspirone, to pregnant rats. These investigations demonstrated that postnatal (PN) 19 and/or 35 day ethanol-exposed offspring had a significant decrease in [3H]citalopram binding to 5-HT reuptake sites in the frontal cortex, parietal cortex, lateral hypothalamus, substantia nigra, medial septum, and striatum. In contrast, [3H]citalopram binding was increased in the dorsal raphe on PN5 and in the median raphe on PN19. No significant ethanol-associated changes were detected in the hippocampus CA3 region or in the amygdala. When [3H]citalopram binding was compared in the offspring of saline- and buspirone-treated dams, it appeared that maternal treatment with buspirone prevented or reversed most of the ethanol-associated developmental abnormalities in 5-HT reuptake sites. Buspirone prevented the decline in binding of [3H]citalopram in the frontal cortex, lateral hypothalamus, substantia nigra and medial septum. Similarly, buspirone treatment prevented the ethanol-associated increase in binding in the dorsal and median raphe. Additional experiments are needed to elucidate the impact of maternal buspirone treatment on the development of other neurotransmitter systems in offspring.
Kim
J A
JA
Neuroscience Program, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
Druse
M J
MJ
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000254:growth & development*; D001923:Brain Chemistry / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D015283:Citalopram / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D002065:Buspirone; D002492:Central Nervous System Depressants; D015283:Citalopram; D000431:Ethanol; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors