Determination of an Estradiol Dose-Response Relationship in the Modulation of Ethanol Intake

Authors

  • Matthew M. Ford,

    Corresponding author
    1. Portland Alcohol Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
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  • J. C. Eldridge,

    1. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon; and the Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
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  • Herman H. Samson

    1. Center for the Neurobehavioral Study of Alcohol, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
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  • Supported through Grants P50AA11997 (HHS) and T32AA07565 (MMF) awarded by the NIAAA.

Matthew M. Ford, PhD, Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97239; Fax: 503-273-5351; E-mail: fordma@ohsu.edu.

Abstract

Abstract: Background: Estradiol (E2) potentiates the self-administration of numerous psychoactive drugs in female rodents. An analogous modulatory role of E2 on ethanol consumption remains unresolved because of examination of limited doses. The purpose of this study was to delineate a dose-response relationship for E2 on ethanol intake with an extended range and number of E2 doses.

Methods: Female Long-Evans rats had continuous access (22 hr/day) to both 10% ethanol (10E) solution and water. After the establishment of stable 10E intake baselines, rats were assigned to one of seven dose groups balanced for 10E intake [sham-operated (Shm) or ovariectomized (Ovx) plus E2 (μg/kg)]: Shm + 0, Ovx + 0, Ovx + 0.05, Ovx + 0.15, Ovx + 0.5, Ovx + 1.5, and Ovx + 5. Ethanol preference drinking was evaluated during 25 consecutive days of E2 replacement treatment, and trunk blood was collected for the determination of plasma E2 and progesterone concentrations.

Results: Chronic E2 replacement regimens (0.05–1.5 μg/kg) dose-dependently augmented 10E intakes and ethanol preference ratios without concomitantly altering water consumption. Despite the maintenance of 2- to 3-fold greater plasma E2 levels, a supraphysiologic E2 dose (5 μg/kg) failed to precipitate ethanol intakes in excess of levels observed after treatment with a high physiologic E2 dose (1.5 μg/kg). Plasma progesterone concentrations were significantly increased in treatment groups (1.5 and 5 μg/kg E2) that exhibited corresponding significant increases in ethanol consumption.

Conclusions: A positive dose-response relationship between E2 and ethanol intake (incremental increases in E2 dose corresponded to incremental increases in intake) was apparently limited to a physiologic concentration range, because a supraphysiologic dose failed to elicit an additional stepwise increase in ethanol intake. These findings stipulate a modulatory role for E2 in the regulation of moderate ethanol intake and suggest that endogenous fluctuations of E2 may alter the propensity toward consumption in women and in female animal models of ethanol self-administration.

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