THE EFFECT OF EXPOSURE TO REPETITIVE UNPREDICTABLE STRESSFUL STIMULI ON THE FREE-CHOICE CONSUMPTION OF ETHANOL AND OTHER MOOD-ALTERING DRUGS (HPA AXIS, ACTH)
Abstract
The effects of exposure to repetitive irregular/unpredictable stressful stimuli on the free-choice consumption of ethanol were studied in rats given a choice of consuming either 0.1% saccharin (SAC) or 10% ethanol in 0.1% saccharin (ETOH). Stressful stimuli were isolation in a novel environment (ISO) and immobilization (IMM), presented randomly over a two week period of time. During stressor exposure no differences were detected in the volume of ethanol consumed by: control/nonstressed (CON), ISO or IMM. During the two weeks following the last exposure to stressful stimuli, the animals in both stressed groups consumed significantly greater quantities of ethanol as compared to nonstressed controls. The post-stress induced consumption of ethanol was consistent and reproducible. Since stressful stimuli also activate the hypothalamic-pituitary-adrenocortical (HPA) axis, a systematic evaluation of the HPA axis and its involvement in ethanol consummatory behavior was undertaken. Exposure to repetitive irregular stressful stimuli did not induce the free-choice consumption of ethanol in hypophysectomized (HPX) or chronic dexamethasone-treated (DEX) rats. The results in adrenalectomized (ADX) rats mirrored those of intact animals; that is ADX animals exposed to repetitive unpredictable stress consumed increasing quantities of ethanol during the post-stress period. Repeated intravenous administration of exogenous ACTH also induced ethanol-consuming behavior, post-administration. When ethanol was replaced (as one drinking solution) by either d-amphetamine, methamphetamine or phenylpropanolamine, exposure to repetitive irregular stressful stimuli did not induce the free-choice consumption of drug either during or after stressor presentation. In summary, rats exposed to repetitive unpredictable stress increase their free-choice consumption of ethanol following cessation of exposures to stress. Chronic DEX treatment or HPX blocks the post-stress increase in ethanol consumption; ADX rats mimic the results obtained with intact animals. Repetitive administration of ACTH induces ethanol consuming behavior in rats which increases upon discontinuation of ACTH injections. The results suggest that the hormones secreted from the pituitary gland, specifically ACTH, play a critical role in the initiation of ethanol-consummatory behavior seen in stressed animals. No stress-induced consumption of any phenethylamine was seen; therefore the abuse of different pharmacological classes of drugs may depend on their "stress-reducing" properties.
Degree
Ph.D.
Subject Area
Pharmacology
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