Fetal Ethanol Exposure: Hypothalamic‐Pituitary‐Adrenal and β‐Endorphin Responses to Repeated Stress

Abstract

Previous studies provide evidence that fetal ethanol exposure induces hypothalamic-pituitary-adrenal (HPA) and pituitary beta-endorphin (beta-EP) hyperresponsiveness to acute stressors. The present study demonstrates significant effects of in utero ethanol exposure on the parallel response patterns of the HPA axis and the pituitary beta-EP system to repeated exposures to a stressor, restraint stress, and indicates sex differences in response. Together, data from the two experiments indicate that, after repeated restraint exposures, fetal ethanol-exposed (E) males and females both show significantly increased plasma levels of adrenocorticotropin (ACTH), and E males also show significantly increased plasma levels of beta-endorphin-like immunoreactivity (beta-EPLIR), compared with their respective pair-fed and control counterparts. Marginal increases in the corticosterone response of E males and the beta-EPLIR response of E females, compared with their controls, were also observed. In addition, delayed or deficient habituation to restraint stress was observed in the beta-EPLIR response of E males and the ACTH response of E females. These data demonstrate that fetal E-exposed males and females both exhibit hormonal hyperresponsiveness and/or deficits in recovery after repeated exposures to restraint stress, but that the patterns of response may differ depending on the number and duration of restraint exposures, the time course measured, and whether the endpoint measured is corticosterone, ACTH, or beta-EPLIR. In addition, the finding that E and pair-fed animals both differed from their respective controls in certain developmental and hormonal measures suggests that prenatal nutritional factors may play a role in mediating some of the changes that are observed.

Ethanol Induces Apoptotic Death of Developing β-Endorphin Neurons via Suppression of Cyclic Adenosine Monophosphate Production and Activation of Transforming Growth Factor-β1-Linked Apoptotic Signaling

“…It has been shown that the neurotransmitter system that regulates the neuroendocrine response to stress is especially vulnerable to ethanol during the developmental period in rats. Behavioral and neurochemical studies indicate that defects in the ability of these rats to respond appropriately to stress seem to be because of alterations in the function of hypothalamic peptides (Weinberg et al, 1996). ␤-EP is one of these peptides that participates in bringing about the body's homeostasis after a stress response (Plotsky, 1986).…”

Behavioral deficits associated with fetal alcohol exposure are reversed by prenatal thyroid hormone treatment: a role for maternal thyroid hormone deficiency in FAE

“…First, FAE offspring are known to be stress-hyper-responsive. 47,48 Hence, a visual platform test at the beginning of the training could affect the results of the spatial learning task differentially. Presenting the visual platform at the end of the training would not differentiate the learning impairment from the visual impairment.…”

Exposure to Repeated, Intermittent d-amphetamine Induces Sensitization of HPA Axis to a Subsequent Stressor

“…Animal and human studies have demonstrated that environmental manipulation, such as exposure to alcohol or stress during the pre-and early postnatal period (Liang and Boyce 1993;Weinberg et al 1996;Day et al 1998), can modify an organism's response to stressors. Such manipulations may lead to an increased reactivity to stressors ("sensitization"), which can be expressed both behaviourally and neurochemically (Pitman et al 1990;Badiani et al 1996;Pani et al 2000).…”

“…A wealth of evidence suggests that an increased reactivity to stressors and/or the inability to respond effectively and appropriately to stressors plays an important role in the development and expression of many forms of mental illness (Ehlert and Straub 1998;Kreek and Koob 1998;Dohrenwend 2000;Heim et al 2000). Clearly, a better understanding of the underlying neurobiology of this sensitivity to stressors may help in the prophylaxis and treatment of these disorders.Animal and human studies have demonstrated that environmental manipulation, such as exposure to alcohol or stress during the pre-and early postnatal period (Liang and Boyce 1993;Weinberg et al 1996;Day et al 1998), can modify an organism's response to stressors. Such manipulations may lead to an increased reactivity to stressors ("sensitization"), which can be expressed both behaviourally and neurochemically (Pitman et al 1990;Badiani et al 1996;Pani et al 2000).…”