Increased Activity of the Hypothalamic-Pituitary-Adrenal Axis of Rats Exposed to Alcohol in Utero: Role of Altered Pituitary and Hypothalamic Function

Lee, Soon; Schmidt, Donne; Tilders, F. J. H.; Rivier, Catherine

doi:10.1006/mcne.2000.0890

Cited by 79 publications

(111 citation statements)

References 73 publications

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“…Previous work carried out in our laboratory had demonstrated that FAE mice (Kang et al, 2004) and rats (Lee et al, 2000a) released more ACTH in response to footshocks. In the present work, we only observed a significant main effect of FAE in female rats [F(1, 48) = 4.591, p = 0.037] (n = 6-7/group) ( Figure 1B).…”

Section: Effect Of Fae On Shock-induced Acth Releasementioning

confidence: 78%

“…The day on which a plug was found was designated as day 0 of gestation. Females assumed to be pregnant were divided into two groups: one control group and one group exposed to vapour alcohol for 6 consecutive hours (0700-1300) per day on gestational days 7-18 (Lee et al, 2000a). Vapour alcohol levels were increased daily in the chambers until maternal blood alcohol levels (BALs) reached 180-200 mg/dl, and were then maintained at these levels.…”

Section: Experimental Procedures Animals and Alcohol Exposurementioning

confidence: 99%

“…We used individual alcohol vapour chambers provided by La Jolla Alcohol Research, Inc. (La Jolla, CA, http://www.ljari.com), which we have validated for use in both adult male rats (Lee et al, 2000b) and pregnant animals (Lee et al, 2000a).…”

Section: Alcohol Treatmentmentioning

confidence: 99%

“…The upregulated activity of the HPA axis that is observed in adult rodents exposed to alcohol prenatally could therefore result from changes at the level of the PVN, pituitary and/or adrenal. While still controversial, at least in adrenal-intact animals (Lee et al, 2000a), possible alterations in pituitary sensitivity to its trophic factors remain Halasz et al, 1997;Osborn et al, 2000;Glavas et al, 2001) but probably only play a modest role. Indeed, at present, the most convincing evidence suggests that at least in rats, prenatal alcohol primarily increases CRF gene expression in PVN neurons (Gabriel et al, 2000;Lee et al, 2000a).…”

Section: Introductionmentioning

confidence: 99%

“…While still controversial, at least in adrenal-intact animals (Lee et al, 2000a), possible alterations in pituitary sensitivity to its trophic factors remain Halasz et al, 1997;Osborn et al, 2000;Glavas et al, 2001) but probably only play a modest role. Indeed, at present, the most convincing evidence suggests that at least in rats, prenatal alcohol primarily increases CRF gene expression in PVN neurons (Gabriel et al, 2000;Lee et al, 2000a). It also alters the activity of CRF neurons, which may be achieved by changes in PVN neuron responsiveness to stimuli, the neuronal input to the PVN and/or PVN responsiveness to secretagogues.…”

Section: Introductionmentioning

confidence: 99%

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Novel role of adrenergic neurons in the brain stem in mediating the hypothalamic–pituitary axis hyperactivity caused by prenatal alcohol exposure

2008

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Exposure to alcohol during embryonic development leads to changes in the hypothalamicpituitary-adrenal (HPA) axis such that adult offspring release more adrenocorticotrophic hormone (ACTH) than controls when exposed to stress. In the present work, we tested the hypothesis that changes in the activity of the catecholaminergic system modulate, at least in part, this upregulation of the HPA axis. Pregnant Sprague Dawley rats were exposed to alcohol 6 hours daily during gestation days 7-18 using the vapour chamber model, which generated mean blood alcohol levels of 188.6 ± 10 mg/dl. All experiments were performed on 2-3 month-old offspring. We measured the ACTH response to intracerebroventricular injection of adrenergic receptor agonists. In rats exposed to footshocks, we investigated the activity of corticotrophin-releasing factor (CRF) as well as indexes of catecholamine immunoreactivity, namely tyrosine hydroxylase (TH) immunopositive neurons in the paraventricular nucleus (PVN), TH immunopositive neurons in the locus coeruleus, and phenylethanolamine N-methyltransferase (PNMT) immunopositive neurons in the brain stem. While adult females exposed to alcohol during fetal development (FAE) displayed the expected enhanced ACTH response to stress, there were no significant differences in response to adrenergic receptor agonists or in shock-induced CRF/TH immunoreactivity (ir) and neuronal activity, as determined by c-fos colocalization. In contrast, FAE female offspring exposed to footshocks showed a significant increase in the activity of adrenergic neurons in the C1 region of the brain stem, a population of cells that project to the PVN. Collectively, these results suggest that while FAE-induced hyperactivity of the HPA axis is not accompanied by significant changes in CRF or TH-ir neurons, it is characterized by an upregulation of C1 adrenergic neurons of the brain stem. This novel finding should lead to the functional characterization of this brain region in the FAE model.

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Section: Effect Of Fae On Shock-induced Acth Releasementioning

confidence: 78%

Section: Experimental Procedures Animals and Alcohol Exposurementioning

confidence: 99%

Section: Alcohol Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Novel role of adrenergic neurons in the brain stem in mediating the hypothalamic–pituitary axis hyperactivity caused by prenatal alcohol exposure

2008

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Direct and Indirect Mechanisms of Alcohol Teratogenesis: Implications for Understanding Alterations in Brain and Behavior in FASD

Uban

Bodnar

Butts

et al. 2010

Fetal Alcohol Spectrum Disorder

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Long‐term depression in vivo: Effects of sex, stress, diet, and prenatal ethanol exposure

Titterness

Christie

2008

Hippocampus

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Long-term depression (LTD) of synaptic efficacy has proven a difficult phenomenon to examine in vivo, despite the ease with which it is induced in a variety of in vitro preparations. Prior exposure to an acute stressful episode does however seem to enhance the capacity of the hippocampus to exhibit LTD in vivo in male animals. In the present experiments, we examined the capacity for low-frequency stimuli (low-frequency stimulation (LFS)) to induce LTD in juvenile male and female animals following an acute stress episode. Interestingly, prior exposure to stress was only required for the induction of LTD in male animals, while both control and stressed female animals exhibited equivalent LTD. In animals that were exposed to ethanol in utero, a similar requirement for prior exposure to stress to elicit LTD was found for male, but not female animals. This prenatal ethanol exposure did not in itself alter the capacity for LTD induction in either sex; however, in utero food restriction did enhance LTD induction in both male and female animals, irrespective of whether they were exposed to stress just prior to being administered LFS. These results indicate that in utero dietary restriction more drastically affects CA1 LTD than in utero ethanol exposure. In addition, female animals seem to exhibit LTD in vivo in the absence of stress much more easily than their male counterparts.

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Increased Activity of the Hypothalamic-Pituitary-Adrenal Axis of Rats Exposed to Alcohol in Utero: Role of Altered Pituitary and Hypothalamic Function

Cited by 79 publications

References 73 publications

Novel role of adrenergic neurons in the brain stem in mediating the hypothalamic–pituitary axis hyperactivity caused by prenatal alcohol exposure

Novel role of adrenergic neurons in the brain stem in mediating the hypothalamic–pituitary axis hyperactivity caused by prenatal alcohol exposure

Direct and Indirect Mechanisms of Alcohol Teratogenesis: Implications for Understanding Alterations in Brain and Behavior in FASD

Long‐term depression in vivo: Effects of sex, stress, diet, and prenatal ethanol exposure

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