Prenatal ethanol exposure in rats alters serotonergic-mediated behavioral and physiological function

Abstract

Our findings indicate that prenatal ethanol exposure alters 5-HT(1A) and 5-HT(2A) receptor function in adulthood and does so in a sex-specific manner. These findings have important implications for altered hormonal and behavioral responsiveness observed in ethanol-exposed animals.

Hypothalamic–Pituitary–Adrenal Responses to 5‐HT1A and 5‐HT2A/C Agonists Are Differentially Altered in Female and Male Rats Prenatally Exposed to Ethanol

“…Data from our lab (Hofmann et al, 2005;Weinberg, 1988Weinberg, , 1992Weinberg et al, 1996) and others Lee and Rivier, 1996) have shown that the prenatal ethanol exposure may differentially alter the HPA response pattern of females and males depending on the experimental time course, the stressor, and the hormonal endpoint measured Zhang et al, 2005). Furthermore, we have shown that DOI-induced ''wet dog shakes'' are increased in E females but not E males (Hofmann et al, 2002), and that there are sex differences in prenatal ethanol effects on anxiety and anxiolytic responses to 8-OH-DPAT (Hofmann et al, 2005). Together, these data suggest that the gonadal steroids play a role in mediating the differential effects of ethanol on females and males, and that females may be more vulnerable to the effects of in utero exposure to ethanol on 5-HT receptor-mediated responses.…”

“…Treatment with 5-HT agents normalizes many of the neuroendocrine abnormalities (Holsboer, 1999;Holsboer and Barden, 1996;Keck and Holsboer, 2001;Maes et al, 1995;Nemeroff and Owens, 2004;Rybakowski and Twardowska, 1999;Weizman et al, 1988), and the response to 5-HT has been used as a marker of clinical improvement following drug treatment (Bhagwagar et al, 2002;Raap and Van de Kar, 1999). Data from our laboratory have shown altered physiological and behavioral responses to the 5-HT 1A agonist 8-OH-DPAT (Hofmann et al, 2002) as well as an increase in anxiety-like behavior and anxiolytic responses to 8-OH-DPAT in E compared with control animals (Hofmann et al, 2005). Together with the present data showing that E animals have altered ACTH responses to 5-HT agonists and 5-HT 1A receptor mRNA expression, these findings suggest that E animals have altered 5-HT-HPA interactions, and/or an imbalance between 5-HT 1A and 5-HT 2A receptor function (Lanfumey et al, 2000;Zhang et al, 2005).…”

“…The finding that E females have opposite patterns of response to 8-OH-DPAT and DOI was unexpected. Our previous data showed that E females exhibit both an increased 8-OH-DPAT-induced hypothermic response and increased DOI-induced ''wet dog shakes'' compared with controls, (Hofmann et al, 2002), and therefore we hypothesized that an ACTH increase in response to both agonists would be observed.…”

“…Similarly, decreased numbers of 5-HT neurons, reduced serotonergic innervation, and compromised development of the forebrain along the serotonergic pathway were reported in mouse pups exposed to ethanol in utero (Sari and Zhou, 2004;Zhou et al, 2005). Finally, our laboratory has recently shown that prenatal ethanol exposure increases hypothermic responses to the 5-HT 1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and ''wet dog shakes'' in response to the 5-HT 2A/C agonist, (1)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI; Hofmann et al, 2002), and increases anxiety-like behavior in adulthood, which is in part mediated by the 5-HT 1A receptor (Hofmann et al, 2005).…”

Altered responsiveness of serotonin receptor subtypes following long-term cannabinoid treatment

“…Twenty-four hours following the final injection, both groups were then divided into three subgroups : (1) vehicle (0.9 % saline) ; (2) 0.3 mg/kg 8-hydroxy-2-(N,N-dipropylamino)tetralin (8-OH-DPAT ; a 5-HT 1A receptor agonist ; Sigma-Aldrich, Oakville, ON, Canada) ; (3) 1 mg/kg ((1-)2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI ; a 5-HT 2A/2C receptor agonist ; Sigma-Aldrich). These doses were based on previous psychopharmacological studies and are within normal testing range (Akiyoshi et al, 1995 ;Hofmann et al, 2002 ;Mikklesen et al, 2004). Separate cohorts of animals were used for the hormonal studies (n=5 per group) and the behavioural/ thermal (n=7 per group) studies.…”