Chronic mild stress increases alcohol intake in mice with low dopamine D2 receptor levels.

Abstract

Alcohol use disorders emerge from a complex interaction between environmental and genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to play a central role in alcoholism. To better understand the interactions between DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at the end of the experiment, the animals were tested in the forced swim and open field tests. We measured ethanol intake and preference, immobility in the force swim test, and activity in the open field. We show that under no CMS, Drd2+/- and Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+. Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had significantly lower activity in the open field than Drd2+/+, whereas no genotype differences were observed in the forced swim test. Exposure to CMS increased immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed in open field test measures. These findings suggest that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood.

Dopamine and glucose, obesity, and reward deficiency syndrome

“…While, for example, high levels of enkephalins are associated with pain suppression and low serotonin levels with depression, an individual with the Taq1 A1 allele of the Dopamine Receptor Gene ( DRD2 ), lacks enough dopamine receptor sites to release the normal amount of dopamine into the Reward Center of the brain and dopamine function is reduced (Noble et al, 1991; Delis et al, 2013). Humans possessing the A1 variant crave and seek substances and behaviors known to cause dopamine release preferentially at the nucleus accumbens (NAc) in the meso-limbic system (Stice and Dagher, 2010).…”

“…They may become serious cocaine abusers or have unhealthy appetites, which lead to, eating disorders like obesity, overeating or at the other extreme, anorexia nervosa (AN), they also suffer from high levels of stress over an extended period of time. To activate their dopaminergic pathways, a self-healing process to offset their low D2 receptors, individuals are driven to engage in activities which will increase brain dopamine function (Noble et al, 1991, 1993; Delis et al, 2013). The consumption of alcohol in large quantities or carbohydrate binging stimulates the brain’s production of and utilization of dopamine (Blum et al, 1996, 2000).…”

Reward Deficiency Solution System (RDS): A Tale of Three Scientists

“…Along these lines Delis et al [25] observed that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood this also supports dopamine agonist therapy not antagonistic. Moreover, recent work by Willuhn et al [26] surprisingly found that phasic dopamine decreased in the ventral medium striatum (VSM) as the rate of cocaine intake increased, with the decrement in dopamine in the VMS significantly correlated with the rate of escalation.…”

Reward Deficiency Syndrome (RDS): Is there a Solution?

“…It is our hypothesis that D2 receptor stimulation In fact, stress and dopamine D2 receptor levels play a significant role in alcohol seeking behaviors. Delis et al [39] observed that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake. Under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood, which further supports dopamine agonist therapy.…”