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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This laboratory previously demonstrated that in utero ethanol exposure markedly impairs the development of the serotonergic system in rat brain. Developmental abnormalities could be detected as early as G15 in the brainstem and G19 in the cortex. Because of the importance of fetal serotonin (5-HT) and 5-HT1A receptors for the normal development of 5-HT containing neurons, we initiated studies to determine whether administration of a 5-HT1A agonist, buspirone, to pregnant rats could overcome the adverse effects of in utero ethanol exposure on the developing serotonergic system in offspring. Female, Sprague-Dawley rats were given daily subcutaneous injections of buspirone (4.5 mg/kg) from gestational day 13 (G13) to G20. 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content were determined in the cortex and cortical regions. These experiments demonstrated that the ethanol-associated abnormalities in the development of the serotonergic system can be partially overcome by in utero exposure to buspirone. Specifically, whereas untreated ethanol rats had a deficiency of 5-HT and/or 5-HIAA in whole cortex on PN5, and in the motor cortex on PN19 and 35, no significant differences were detected in these regions of the age-matched offspring of buspirone-treated, ethanol-fed rats. In contrast, the 5-HT and 5-HIAA deficiency in the somatosensory cortex of 19-day-old offspring of ethanol-fed rats was not corrected by in utero buspirone treatment. These results suggest that the abnormal development of cortical projections of serotonergic neurons may be due in part to the low fetal 5-HT content in ethanol-exposed rats and may potentially be overcome by in utero treatment with a 5-HT1A agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of pregnant alcohol-consuming rats with buspirone: effects on serotonin and 5-hydroxyindoleacetic acid content in offspring. 768 Aug 41

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.
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PMID:Protective effects of maternal buspirone treatment on serotonin reuptake sites in ethanol-exposed offspring. 873 26