The Effect of Telmisartan, an angiotensin receptor blocker, on Alcohol Consumption and Alcohol-Induced Dopamine Release in the Nucleus Accumbens.

Abstract

Alcohol use disorder remains a major health problem. Mesocorticolimbic dopaminergic system including nucleus accumbens region and multiple neural circuits are involved in its complex underlying mechanism. For instance, alcohol intake stimulates central and peripheral renin-angiotensin system and increases angiotensin II levels, which predominantly affect angiotensin 1 receptors both in periphery and brain. In this study, we aimed to investigate the effects of intracerebroventricularly administered angiotensin 1 receptor blocker telmisartan on the alcohol consumption of male Sardinian alcohol-preferring (sP) rats and on the alcohol-induced dopamine levels in the nucleus accumbens region in Wistar rats. Acute intracerebroventricularly administration of telmisartan (100 nM) reduced the alcohol intake for 24 hours without affecting food and water consumption in sP rats. Acute intracerebroventricularly injection of the opioid receptor antagonist naloxone (75 nM), tested as a reference compound, also reduced the alcohol consumption in sP rats; however, naloxone s effect lasted only for 30 min. In microdialysis experiments, telmisartan administered intracerebroventricularly did not change dopamine levels in nucleus accumbens induced by acute intraperitoneal alcohol administration in Wistar rats. According to these results, further studies are needed to elucidate the role of renin-angiotensin system on alcohol use disorder pathophysiology.