Prenatal ethanol exposure: Sex differences in anxiety and anxiolytic response to a 5-HT1A agonist

Hofmann, Candace E.; Patyk, Izabella A.; Weinberg, Joanne

doi:10.1016/j.pbb.2005.10.010

Cited by 31 publications

(37 citation statements)

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“…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).…”

Section: Discussionmentioning

confidence: 95%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

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Hypothalamic–Pituitary–Adrenal Responses to 5‐HT_1A and 5‐HT_2A/C Agonists Are Differentially Altered in Female and Male Rats Prenatally Exposed to Ethanol

Hofmann

Ellis

et al. 2007

Alcoholism Clin & Exp Res

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Hypothalamic–Pituitary–Adrenal Responses to 5‐HT_1A and 5‐HT_2A/C Agonists Are Differentially Altered in Female and Male Rats Prenatally Exposed to Ethanol

Hofmann

Ellis

et al. 2007

Alcoholism Clin & Exp Res

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“…Apparently, these detrimental effects are obtained when ethanol is chronically administered during gestation or when relatively high ethanol doses are employed during a temporal window of brain vulnerability to the teratogenic properties of this drug (e.g. Hofmann, Patyk, & Weinberg, 2005;Hunt & Phillips, 2004).…”

Section: Discussionmentioning

confidence: 99%

Acute sensitivity and acute tolerance to ethanol in preweanling rats with or without prenatal experience with the drug

Arias

Molina

Mlewski

et al. 2008

Pharmacology Biochemistry and Behavior

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The present study examined behavioral sensitivity and acute tolerance to ethanol in infants with or without a moderate prenatal ethanol experience. During gestational days 17-20 dams received 0.0 or 2.0 g/kg ethanol. On postnatal day 13 pups were administered 0.0, 0.5 or 2.5 g/kg ethanol prior to assessment of locomotion. One third of the pups were evaluated at 5-10, 30-35 and 60-65 min after ethanol administration; another third was tested only during the last two post-administration periods; and the remaining third was tested only at 60-65 min. At 30-35 min blood ethanol levels were similar to those attained at 60-65 min. The main results of the study were: (a) The 2.5 g/kg ethanol dose induced biphasic motor effects: stimulation 5-10 minutes after drug administration and sedation after 30-35 or 60-65 minutes. (b) Infants exhibited acute tolerance to ethanol's sedative effects. (c) Although pups prenatally treated with ethanol exhibited heightened locomotor activity levels, acute sensitivity and tolerance were not affected by prenatal treatment. In summary, infants are sensitive to biphasic motor consequences of ethanol and readily exhibit acute tolerance to ethanol's sedative effects. In addition, moderate prenatal ethanol exposure was sufficient to induce hyper-reactivity in the offspring without affecting habituation. KeyboardsPrenatal ethanol; ethanol acute sensitivity; ethanol acute tolerance; locomotor activity; habituation; infant and rat There is a considerable body of experimental evidence indicating that prenatal exposure to ethanol can critically modulate subsequent ethanol intake. This association between prenatal ethanol exposure and later affinity for the drug has been detected in various strains of rats and mice when using a variety of modes of ethanol exposure during pregnancy (Chotro, Arias, & Laviola, 2007). Heightened ethanol consumption resulting from gestational exposure to ethanol has been observed through tests conducted during different ontogenetic periods, including infancy, adolescence and adulthood (Chotro et al., 2007;. Recent epidemiologic studies have found results analogous to those reported in this preclinical research. Even when controlling genetic and environmental factors known to modulate ethanol * Corresponding author. Center for Developmental Psychobiology, Binghamton University, Binghamton, NY 13902-6000, USA Email Address afelicidade@yahoo.es. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript affinity, prenatal exposure to ethanol st...

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“…Of note, PAE animals are hyperresponsive to stressors and show central dysregulation of HPA function in a manner consistent with that observed in major depressive disorder (Hellemans et al, 2008; Weinberg et al, 2008). Furthermore, PAE induces physiological and behavioral abnormalities consistent with altered HPA and 5-HT function, including lack of response inhibition, and increased depressive-/anxiety-like behaviors (e.g., Hellemans et al, 2008; Hofmann et al, 2002, 2005; Weinberg et al, 2008). …”

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Prenatal Alcohol Exposure Results in Long-Term Serotonin Neuron Deficits in Female Rats: Modulatory Role of Ovarian Steroids

Śliwowska

Song

Bodnar

et al. 2013

Alcohol Clin Exp Res

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Background Previous studies on male rodents found that prenatal alcohol exposure (PAE) decreases the number of serotonin immunoreactive (5-HT-ir) neurons in the brainstem. However, data on the effects of PAE in females are lacking. In light of known sex differences in responsiveness of the 5-HT system and known effects of estrogen (E2) and progesterone (P4) in the brain, we hypothesized that sex steroids will modulate the adverse effects of PAE on 5-HT neurons in adult females. Methods Adult females from 3 prenatal groups (Prenatal alcohol-exposed [PAE], Pair-fed [PF], and ad libitum-fed Controls [C]) were ovariectomized (OVX), with or without hormone replacement, or underwent Sham OVX. 5-HT-ir cells were examined in key brainstem areas. Results Our data support the hypothesis that PAE has long-term effects on the 5-HT system of females and that ovarian steroids have a modulatory role in these effects. Intact (Sham OVX) PAE females had marginally lower numbers of 5-HT-ir neurons in the dorsal raphe nucleus of the brainstem compared with PF and C females. This marginal difference became signiffcant following removal of hormones by OVX. Replacement with E2 restored the number of 5-HT-ir neurons in PAE females to control levels, while P4 reversed the effects of E2. Importantly, despite these differential responses of the 5-HT system to ovarian steroids, there were no differences in E2 and P4 levels among prenatal treatment groups. Conclusions These data demonstrate long-term, adverse effects of PAE on the 5-HT system of females, as well as differential sensitivity of PAE compared with control females to the modulatory effects of ovarian steroids on 5-HT neurons. Our findings have important implications for understanding sex differences in 5-HT dysfunction in depression/anxiety disorders and the higher rates of these mental health problems in individuals with fetal alcohol spectrum disorder.

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Prenatal ethanol exposure: Sex differences in anxiety and anxiolytic response to a 5-HT1A agonist

Cited by 31 publications

References 47 publications

Hypothalamic–Pituitary–Adrenal Responses to 5‐HT_1A and 5‐HT_2A/C Agonists Are Differentially Altered in Female and Male Rats Prenatally Exposed to Ethanol

Hypothalamic–Pituitary–Adrenal Responses to 5‐HT_1A and 5‐HT_2A/C Agonists Are Differentially Altered in Female and Male Rats Prenatally Exposed to Ethanol

Acute sensitivity and acute tolerance to ethanol in preweanling rats with or without prenatal experience with the drug

Prenatal Alcohol Exposure Results in Long-Term Serotonin Neuron Deficits in Female Rats: Modulatory Role of Ovarian Steroids

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Prenatal ethanol exposure: Sex differences in anxiety and anxiolytic response to a 5-HT1A agonist

Cited by 31 publications

References 47 publications

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

Acute sensitivity and acute tolerance to ethanol in preweanling rats with or without prenatal experience with the drug

Prenatal Alcohol Exposure Results in Long-Term Serotonin Neuron Deficits in Female Rats: Modulatory Role of Ovarian Steroids

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Hypothalamic–Pituitary–Adrenal Responses to 5‐HT_1A and 5‐HT_2A/C Agonists Are Differentially Altered in Female and Male Rats Prenatally Exposed to Ethanol

Hypothalamic–Pituitary–Adrenal Responses to 5‐HT_1A and 5‐HT_2A/C Agonists Are Differentially Altered in Female and Male Rats Prenatally Exposed to Ethanol