The influence of chronic or acute DHEA exposure on β-endorphin levels in the nucleus accumbens

Background: As cocaine dependence becomes highly prevalent among a diverse population, there is a need for innovative treatments that target both the physiological and behavioral aspects of addiction. We have previously published that Dehydroepiandrosterone (DHEA), a neurosteroid, reduces cocaine-seeking behavior and relapse for cocaine use. As drug addiction manifestation is affected by upregulation of β-endorphin levels in the Nucleus Accumbens (NAc), which is vital for the brain's reward system and to the rewarding properties of drugs, the current study aims to determine the effects of DHEA on β-endorphin levels in the NAc and its implications for cocaine addiction treatment. Methods: Utilizing Male Sprague-Dawley rats, DHEA was administered acutely (30 nM and 300 nM) directly into the NAc or as a chronic (14-day) intraperitoneal (i.p.) treatment, and β-endorphin levels were evaluated using microdialysis. Results: Our results revealed that acute DHEA administration significantly increased β-endorphin levels in the NAc, similar to the response elicited by cocaine. Conversely, chronic DHEA treatment prevents cocaine-induced β-endorphin upregulation in the NAc. Conclusions: Our findings reveal the dual mechanisms by which DHEA alters β-endorphin levels, highlighting its potential as a therapeutic agent to decrease the rewarding effects of cocaine, by maintaining β-endorphin stability in the NAc. This novel insight may explain the mechanism by which DHEA reduces drug-seeking behavior, suggesting that DHEA may be a viable candidate for the treatment of cocaine addiction.