Effects of maternal ethanol consumption and buspirone treatment on 5-HT1A and 5-HT2A receptors in offspring.
In utero ethanol exposure results in a decreased concentration of serotonin (5-HT) in brain regions containing the cell bodies of 5-HT neurons and their cortical projections. The concentration of 5-HT reuptake sites is also reduced in several brain areas. The present study extended prior work by evaluating the effects of chronic maternal ethanol consumption and maternal buspirone treatment on 5-HT1A and 5-HT2A receptors in multiple brain areas of offspring. Receptors were quantitated early in postnatal development and at an age when the 5-HT networks are normally well-established. Because fetal 5-HT functions as an essential neurotrophic factor, these studies also determined whether treatment of pregnant rats with buspirone, a 5-HT1A agonist, could overcome the effects of the fetal 5-HT deficit and prevent ethanol-associated receptor abnormalities. The results demonstrated that in utero ethanol exposure significantly alters the binding of 0.1 nM [3H]-8-hydroxy-dipropylaminotetralin to 5-HT1A receptors in developing animals. Ethanol impaired the development of 5-HT1A receptors in the frontal cortex, parietal cortex, and lateral septum; these receptors did not undergo the normal developmental increase between postnatal days 19 and 35. The dentate gyrus was also sensitive to the effects of in utero ethanol exposure. 5-HT1A receptors were increased in this region at 19 days. Maternal buspirone treatment prevented the ethanol-associated abnormalities in 5-HT1A receptors in the dentate gyrus, frontal cortex, and lateral septum. Neither maternal ethanol consumption nor buspirone treatment altered the binding of 2 nM [3H]ketanserin to 5-HT2A receptors in the ventral dentate gyrus, dorsal raphe, parietal and frontal cortexes, striatum, substantia nigra, or nucleus accumbens.
Kim
J A
JA
Neuroscience Program, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA.
Gillespie
R A
RA
Druse
M J
MJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001931:Brain Mapping; D002065:Buspirone / Q000493:pharmacokinetics / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D005865:Gestational Age; D009474:Neurons / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D000431:Ethanol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone