title: A 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, mitigates developmental neurotoxicity of ethanol to serotonergic neurons.
abstract: Prenatal ethanol exposure causes the reduction of serotonergic (5-HTergic) neurons in the midbrain raphe nuclei. In the present study, we examined whether an activation of signaling via 5-HT2A and 5-HT2C receptors during the fetal period is able to prevent the reduction of 5-HTergic neurons induced by prenatal ethanol exposure. Pregnant Sprague-Dawley rats were given a liquid diet containing 2.5 to 5.0% (w/v) ethanol on gestational days (GDs) 10 to 20 (Et). As a pair-fed control, other pregnant rats were fed the same liquid diet except that the ethanol was replaced by isocaloric sucrose (Pf). Each Et and Pf group was subdivided into two groups; one of the groups was treated with 1 mg/kg (i.p.) of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), an agonist for 5-HT2A/2C receptors, during GDs 13 to 19 (Et-DOI or Pf-DOI), and another was injected with saline vehicle only (Et-Sal or Pf-Sal). Their fetuses were removed by cesarean section on GD 19 or 20, and fetal brains were collected. An immunohistological examination of 5-HTergic neurons in the fetuses on embryonic day 20 using an antibody against tryptophan hydroxylase revealed that the number of 5-HTergic neurons in the midbrain raphe nuclei was significantly reduced in the Et-Sal fetuses compared to that of the Pf-Sal and Pf-DOI fetuses, whereas there were no significant differences between Et-DOI and each Pf control. Thus, we concluded that the reduction of 5-HTergic neurons that resulted in prenatal ethanol exposure could be alleviated by the enhancement of signaling via 5-HT2A/2C receptors during the fetal period.
authors.affiliation: Department of Anatomy and Developmental Neurobiology, Tokushima University Graduate School of Biomedical Science, Tokushima, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ishiguro
authors.affiliation: Department of Anatomy and Developmental Neurobiology, Tokushima University Graduate School of Biomedical Science, Tokushima, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakata-Haga
authors.affiliation: Department of Anatomy and Developmental Neurobiology, Tokushima University Graduate School of Biomedical Science, Tokushima, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukui
mesh_terms: D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D015870:Gene Expression; D066267:Midbrain Raphe Nuclei / Q000166:cytology / Q000378:metabolism; D009929:Organ Size; D011247:Pregnancy; D051381:Rats; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D059326:Serotonergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*
chemical_list: D000662:Amphetamines; D015306:Biogenic Monoamines; D044348:Receptors, Serotonin, 5-HT2; D058826:Serotonin 5-HT2 Receptor Agonists; D000431:Ethanol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
keywords: 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane; 5-HTergic neuron; fetal ethanol; midbrain raphe nuclei; rat