TY - JOUR

T1 - Patterns of ethanol intake in male rats with partial dopamine transporter deficiency

AU - Kuiper, L. B.

AU - Roberts, J. B.

AU - Estave, P. M.

AU - Leo, D.

AU - Gainetdinov, R. R.

AU - Jones, S. R.

PY - 2023/12

Y1 - 2023/12

N2 - Mesolimbic 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).

AB - Mesolimbic 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).

KW - Wistar

KW - alcohol use disorder

KW - binge

KW - dopamine

KW - dopamine transporter

KW - drinking

KW - ethanol

KW - fast-scan cyclic voltammetry

KW - hypodopaminergia

KW - intermittent access

KW - locomotor activity

KW - novelty

KW - nucleus accumbens

KW - quinine

KW - reuptake

KW - Alcohol Drinking/genetics

KW - Rats, Wistar

KW - Humans

KW - Dopamine Plasma Membrane Transport Proteins/genetics

KW - Male

KW - Nucleus Accumbens

KW - Dopamine

KW - Ethanol

KW - Rats

KW - Animals

UR - https://www.mendeley.com/catalogue/f3694d7d-ac94-339c-a106-f6daffb235a3/

U2 - 10.1111/gbb.12847

DO - 10.1111/gbb.12847

M3 - Article

C2 - 37461188

VL - 22

JO - Genes, Brain and Behavior

JF - Genes, Brain and Behavior

SN - 1601-1848

IS - 6

M1 - e12847

ER -