Home cage voluntary alcohol consumption increases binge drinking without affecting abstinence-related depressive-like behaviors or operant responding in crossed high alcohol-preferring mice (cHAPs).

Chronic alcohol consumption can lead to tolerance and escalation of drinking in humans and animals, but mechanisms underlying these changes are not fully characterized. Preclinical models can delineate which mechanisms are involved. The chronic intermittent ethanol exposure (CIE) procedure uses forced exposure to vaporized alcohol that elicits withdrawal and increased responding for alcohol in operant tasks in C57BL/6J inbred mice. Chronic two-bottle choice (2BC) drinking in the same strain elicits abstinent-related depression-like behavior, suggestive of allostatic changes. Selected lines such as crossed High Alcohol Preferring (cHAP) mice voluntarily drink to blood alcohol concentrations comparable to those attained in CIE and could be used to assess how alcohol affects these same endpoints without the confounds of involuntary vapor inhalation. In three experiments, we assess how 2BC drinking in cHAP mice affects abstinence-related depressive- and anxiety-like behavior, operant responding for alcohol, and binge consumption using drinking-in-the-dark (DID). We hypothesized that cHAPs with home-cage drinking experience would exhibit more depressive behavior after abstinence, increased responding for alcohol in the operant box, and increased DID intake. Of these, a drinking history increased DID intake in female cHAPs only and increased sucrose preference and intake following abstinence, but had no effects on operant responding or NSFT latency and FST immobility following forced abstinence. These results are consistent with recent findings using slice electrophysiology showing tolerance to alcohol's actions on the dorsolateral striatum following 2BC drinking in female, but not male cHAP mice. Overall, these data suggest that cHAPs may require procedures allowing rapid intoxication, such as DID, to demonstrate changes in alcohol's rewarding effects.