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Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol.

Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol. Research Abstract Details 

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  • Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol. Abstract Text:

    candace e hofmannCandace E Hofmann,linda ellisLinda Ellis,wayne k yuWayne K Yu,joanne weinbergJoanne Weinberg,

    BACKGROUND: Prenatal ethanol exposure alters the development of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA hyper-responsiveness to stressors in adulthood. Prenatal ethanol exposure also alters the development and activity of the serotoninergic (5-HT) system. We have previously shown that 5-HT(1A) and 5-HT(2A/C) receptor-mediated behavioral and physiological function are altered in fetal ethanol-exposed offspring. As there are extensive interactions between the HPA axis and the 5-HT system, the present study tested the hypothesis that prenatal ethanol exposure would alter 5-HT(1A) and 5-HT(2A/C) receptor-mediated HPA function. METHODS: The 5-HT(1A) agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.2 mg/kg), and the 5-HT(2A/C) agonist, (+)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI; 0.3 mg/kg), or vehicle (1 mL/kg) were administered to adult female and male offspring from prenatal ethanol-exposed (E), pair-fed control (PF), and ad libitum-fed control (C) dams. The plasma concentration of adrenocorticotropin (ACTH) and corticosterone (CORT) were determined at 0, 15, 30, 60, and 120 minutes postinjection. In addition, corticotropin releasing hormone (CRH) mRNA expression in the paraventricular nucleus of the hypothalamus, and 5-HT(1A) and 5-HT(2A/C) receptor mRNA expression in the hippocampus and prefrontal cortex, respectively, were determined by in situ hybridization. RESULTS: Ethanol-exposed females showed a blunted ACTH response to 8-OH-DPAT at 15 and 30 minutes, and conversely, an increased ACTH response to DOI at all time points postinjection, compared with PF and C females. Differences among E, PF, and C males failed to reach significance. Centrally, however, DOI resulted in a trend toward lower CRH mRNA levels in E and PF compared with C females, but higher CRH mRNA levels in E compared with control males. There were no differences among prenatal groups in 5-HT(2A) receptor expression in the prefrontal cortex following either 8-OH-DPAT or DOI treatment. However, following 8-OH-DPAT, hippocampal 5-HT(1A) receptor expression was higher in E than in PF females in CA1, with a trend toward higher expression in E than in C females in CA2, whereas following DOI, a prenatal group by subfield interaction suggests lower 5-HT(1A) mRNA levels in E and PF compared with C females in CA1 and the dentate gyrus. CONCLUSIONS: These data are the first to demonstrate that prenatal ethanol exposure has differential long-term effects on 5-HT(1A)-mediated and 5-HT(2A)-mediated neuroendocrine function in females and males, and suggest a sex-specific ethanol-induced alteration in the interaction between the HPA axis and the serotonin system.

    Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol. Publishing Authors By Initials

    ce hofmannCE Hofmann,l ellisL Ellis,wk yuWK Yu,j weinbergJ Weinberg,

    For similar reproductive and urinary physiology: reproduction: sex characteristics research abstracts see: reproductive and urinary physiology: reproduction: sex characteristics research

    PUBMED ID PMID:

    MEDLINE DATE:

    Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Alcoholism, clinical and experimental research

    VOLUME: 31

    Page Numbers: 345-55

    Journal Abbreviation: Alcohol. Clin. Exp. Res.

    ISSN: 0145-6008

    DAY: 3

    MONTH: Feb

    YEAR: 2007

    Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7707242

    Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol. Keywords Mesh Terms:

    KEYWORDS: Sex Characteristics

    MESH TERMS: pharmacology

    Chemical & Substance for Abstract: Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol. Information

    Substance Name: Corticotropin-Releasing Hormone

    Registry Number: 9015-71-8

    Grant and Affiliation Information for Hypothalamic-pituitary-adrenal responses to 5-HT1A and 5-HT2A/C agonists are differentially altered in female and male rats prenatally exposed to ethanol.

    AFFILIATION: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

    Country: England

    England Research PublicationEngland Research Publication

    AGENCY: United States NIAAA

    GRANT: AA07789

    ACRONYM: AA

    MEDLINETA: Alcohol Clin Exp Res

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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