Operant Drinking in Crossed High Alcohol Preferring x High Drinking in the Dark (cHAPxHDID) Mice

Abstract

Selectively bred cHAPxHDID mice were used to investigate if an alcohol drinking history affects operant oral alcohol self-administration. I hypothesized that mice with a history of drinking alcohol via the 2-bottle choice (2BC) procedure would respond at a higher rate for alcohol than mice with a water drinking history. The cHAPxHDID mice were first trained to lever press for 5% ethanol (EtOH) until they consumed at least 0.2 mL on a fixed ratio (FR) of 32. After training, the mice were split and counterbalanced into drinking history and water groups based on the baseline data from the last three consecutive FR32; the history group got access to 20% EtOH and water while the water group only had access to tap water. The 2BC procedure lasted for 15 days, followed by 6 tests performed on different days. Day 1 and 2 were reinforced tests where active lever presses resulted in a reward of 20% EtOH for 5 seconds and inactive lever presses resulted in no outcome. Day 3 was a non-reinforced test, where an active lever press resulted in the sipper coming down, but no reinforcer. On Day 4, all mice received a 1.75 g/kg injection i.p. of 20% EtOH, followed 10 minutes later by placement on the static dowel for ataxia testing; foot slips were recorded. Days 5 and 6 were additional reinforced test days. The animals did not show any escalation in alcohol consumption during 2BC. The active and inactive lever presses showed that the groups did not differ in the number of presses for reward. Additionally, alcohol intake (g/kg) during the test days did not differ. The only difference observed was in foot slips. Animals with a drinking history had significantly fewer foot slips compared to water animals. Overall, the data suggest that chronic alcohol pre-exposure does not affect alcohol reinforcement; it only affects behavioral tolerance.