The mineralocorticoid receptor antagonist spironolactone reduces alcohol self-administration in female and male rats

Pharmacology, Biochemistry, and Behavior
Viren H MakhijaniJoyce Besheer

Abstract

Cortisol/corticosterone and the hypothalamic-pituitary-adrenal (HPA) axis serve an important role in modulating alcohol drinking behaviors. To date most alcohol research has focused on the functional involvement of corticosterone and the glucocorticoid receptor (GR), the primary receptor for corticosterone. Recent studies have indicated that the related mineralocorticoid receptor (MR), which binds both corticosterone and aldosterone, may also play a role in alcohol drinking. Therefore, the purpose of the present study was to test the functional role of MR signaling in alcohol self-administration via pharmacological antagonism of the MR with spironolactone. Male and female Long-Evans rats were trained to self-administer a sweetened alcohol solution (15% (v/v) alcohol +2% (w/v) sucrose). The effects of spironolactone (0, 10, 25, 50 mg/kg; IP) were tested on alcohol self-administration and under "probe extinction" conditions to measure the persistence of responding in the absence of the alcohol reinforcer. Parallel experiments in sucrose self-administration trained rats were used to confirm the specificity of spironolactone effects to an alcohol reinforcer. In female rats spironolactone (50 mg/kg) reduced alcohol self-administrati...Continue Reading

Citations

Sep 3, 2020·The Journal of Pharmacology and Experimental Therapeutics·Vanessa A JimenezKathleen A Grant
Aug 4, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Vanessa A PalzesFelicia W Chi

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