Apremilast reduces binge-like drinking behavior and the motivation for ethanol in a genetic risk model of drinking to intoxication.
AUDs
To test whether PDE4 inhibition reduces binge-like alcohol drinking, we administered apremilast to selectively bred “High Drinking in the Dark” (replicate HDID-1 and HDID-2) mice of both sexes prior to measuring limited access drinking using the widely adopted “Drinking in the Dark” (DID) assay (Next, we found that 2 clinically relevant doses of apremilast, 20 and 40 mg/kg (i.p.) reduced binge drinking and BALs (below 80 mg% — the level of intoxication), in female and male HDID-1 mice (AUDs are characterized by a chronic history of harmful drinking. To determine the efficacy of apremilast in reducing chronic alcohol intake, we tested whether 40 mg/kg (i.p.) of apremilast would reduce binge drinking in HDID-1 mice (of both sexes) over a 4-week period, as compared to baseline drinking levels. Here we saw that 40 mg/kg of apremilast reduced chronic binge-like ethanol intake of female and male HDID-1 mice (To determine whether PDE4 inhibition reduces the motivation for alcohol drinking, we next tested the effects of apremilast in inbred HDID-1 (iHDID-1) mice of both sexes during 2 operant ethanol self-administration tasks: (a) operant responding under a progressive ratio (PR) schedule of reinforcement and (b) quinine-adulterated alcohol responding (To ascertain whether apremilast would reduce compulsive-like responding to alcohol (another facet of human alcohol motivation), mice were tested for quinine-adulterated alcohol responding (see timeline in 