Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor

Abstract

Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or over-representation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose- dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that over-representation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards.

Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

“…These observations highlighted the divergent nature of the two isoforms. Our results were consistent with the findings of Bulwa et al [68] who reported that both D2L and D2S isoforms played differential roles in alcohol and sugar intakes. On the one hand, Chen et al [4] reported that the specific D2 receptor antagonist, sulpiride, stimulated consumption of ethanol.…”

Central Neuropeptide Y Modulates Binge-Like Ethanol Drinking in C57BL/6J Mice via Y1 and Y2 Receptors

“…First, it should also be noted that baseline binge-like ethanol drinking (in vehicle-treated groups) varied between studies, but were within a range that we and others have similarly observed using DID procedures (Bulwa et al, 2011;Lowery et al, 2010;Sparta et al, 2008). Importantly, ethanol intake levels within this range were associated with BEC levels that were approximately at or above the BEC level consistent with binge drinking (80 mg/dl).…”

The gut in the brain: the effects of bariatric surgery on alcohol consumption

“…Together, these data suggest that RYGB induces transcriptional alterations within brain circuits known to regulate dopamine function, alcohol intake, and reward processes. Notably, decreases in the dopamine signaling in the mesoaccumbens dopamine pathway have been linked to increases in appetitive behaviors, as well as increases in subjective pleasure from the use of dopamine-enhancing substances (Bello et al 2011; Bulwa et al 2011; Volkow et al 1999). …”