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Effects of prenatal ethanol exposure in rats on multiple endpoints of central serotonergic function Hofmann, Candace Erica

Abstract

Maternal consumption of alcohol during pregnancy produces a wide range of abnormalities in the offspring. The main objective of this thesis was to examine long-term functional changes in central 5-HT receptor function of female and male rats prenatally exposed to ethanol. Serotonin receptor function was assessed through pharmacological challenge with the 5-HT[sub 1A] and 5-HT[sub 2A] receptor agonists 8-hydroxy-2-(di-npropylamino) tetralin (8-OH-DPAT) and (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), respectively. Adult offspring of Sprague-Dawley rats from prenatal ethanol-fed (E), pair-fed (PF) and ad libitum-fed (C) dams were examined. The first study (Chapter III) investigated 8-OH-DPAT-induced hypothermia and DOI-induced Wet Dog Shakes (WDS). Both E females and males showed a greater hypothermic response to 8-OH-DPAT than PF and C animals. In addition, E females and males also showed less of a differential response to a low and high dose of 8-OH-DPAT than PF and C animals. In response to DOI, E females but not males, showed a significantly greater rate of WDS than PF and C females. The second study (Chapter IV) examined expression of anxiety-like behaviour and the anxiolytic response to 8-OH-DPAT in the novelty-induced suppression of feeding task. There was a marked drop in the number of E animals feeding in the novel environment compared to PF and C animals. The observed increase in anxiety-like behaviour in E females was ameliorated by 8-OH-DPAT, suggesting that expression of anxiety-like behaviour in this task is partially mediated by the 5-HT[sub 1A] receptor. The third study (Chapter V) examined 8-OH-DPAT- and DOI-induced increases in plasma adrenocorticotropin (ACTH) and corticosterone. Corticotropin releasing hormone (CRH) mRNA and 5-HT[sub 1A] and 5-HT[sub 2A] receptor mRNA expression was also measured. E females had an attenuated ACTH response to 8-OH-DPAT, but a potentiated ACTH response to DOI, in comparison to PF and C females. Furthermore, 8-OH-DPAT increased 5-HT[sub 1A] mRNA expression in the hippocampus in E females compared to PF and C females. E males also showed increased CRH mRNA levels in response to DOI. These data indicate that prenatal ethanol exposure results in long-term effects on 5- HT[sub 1A] and 5-HT[sub 2A] receptor-mediated behavioural and physiological function in adult animals and that some of these effects may be sex specific.

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