The role of stress and ACTH (4-10) in free -choice ethanol consummatory behavior in rats
Abstract
The effects of exposure to repetitive irregular, unpredictable immobilization stress or injections of ACTH$\sb{4-10}$ on free choice consumption of ethanol were studied in rats given a choice between 0.2% saccharin and 10% ethanol in 0.2% saccharin. Both stressor exposure and ACTH injections resulted in significant decreases in ethanol consumption during the exposure period followed by a significant rise in the post-stress or post-injection period. Saccharin consumption was not affected by any of the treatments. The metabolically stable and more potent analog of ACTH$\sb{4-9}$, Hoe 427 was also tested in the standardized animal test system. Hoe 427 completely blocked ethanol consumption during the exposure period in male rats; this was followed by a rise in the post-exposure period. This post exposure rise was not observed in the female animals which were exposed to Hoe-427. Examination of the female animals for estrus cycle related patterns in ethanol consummatory behavior demonstrated substantial decreases in consumption in the "proestrus" period. These patterns were abolished on exposure to stress or ACTH$\sb{4-10}$. Syracuse high (SHA) and low avoidance (SLA) strains of animals which had been bred for differences in avoidance behavior, and which would have differences in endogenous levels of ACTH, displayed differences in basal ethanol consumption levels. The SHA animals displayed a dose-related decrease in ethanol consumption in the presence of ACTH$\sb{4-10}$. The SLA animals required larger doses of the peptide to decrease consumption. The interactive effects of dopaminergic, serotonergic and gabaergic agonists and antagonists with stress or ACTH$\sb{4-10}$ were studied. The results seemed to suggest a serotonergic involvement in the effect produced by ACTH$\sb{4-10}$ on ethanol consumption. In summary, ACTH$\sb{4-10}$ seemed to exert some type of control over ethanol intake by rats in a free-choice consummatory paradigm. A hypothetical stress/ACTH$\sb{4-10}$ model of alcoholism which relates the release of ACTH$\sb{4-10}$ during stress to possible activation of the brain reward circuitry and a "priming mechanism" to induce periodic, repeated ethanol consumption has been suggested.
Degree
Ph.D.
Advisors
Maickel, Purdue University.
Subject Area
Pharmacology|Anatomy & physiology|Animals
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