Affiliation:
1. Department of Physiology and Pharmacology Wake Forest School of Medicine Winston‐Salem North Carolina USA
2. Department of Neurosciences University of Mons Mons Belgium
3. Institute of Translational Biomedicine St. Petersburg State University St. Petersburg Russia
4. St. Petersburg University Hospital St. Petersburg State University St. Petersburg Russia
Abstract
AbstractMesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/−) were used in this study. First, using fast‐scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol‐naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/− rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two‐bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/− rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/− males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).
Funder
National Institute on Alcohol Abuse and Alcoholism
Subject
Behavioral Neuroscience,Neurology,Genetics
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