- Browse by Author
Browsing by Author "Winkler, Garrett"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Effect of Drinking History on Reinforced and Extinction Responding in Crossed High Alcohol-Preferring Mice(2022-12) Winkler, Garrett; Grahame, Nicholas; Lapish, Christopher; Logrip, MarianTolerance is a diagnostic criterion for alcohol use disorder (AUD) and dependence and is often measured metabolically or behaviorally by comparing blood ethanol concentrations (BEC) or locomotor performance to an ethanol (EtOH) challenge before and after a drinking history, respectively. To explore another aspect of chronic behavioral tolerance in a family history positive (FH+) model of AUD, crossed High Alcohol Preferring (cHAP) mice were allowed to respond instrumentally for an EtOH reinforcer after either a five-week history of continuous home cage two-bottle choice (2BC) drinking or a concurrent five-week water-drinking period. Additionally, some of these animals were placed back into the operant box after home cage drinking histories to respond in extinction, allowing for the quantification of alcohol-motivated seeking alone in the absence of EtOH taking and its intoxicating effects. The results demonstrate that an alcohol history does not lead to a subsequent increase in active lever responding or inactive lever responding when compared to water-drinking controls. However, female cHAP mice with an EtOH-drinking history respond more on the inactive lever in extinction compared to water controls, suggesting that home cage EtOH history potentiates variation in responding in extinction. Overall, female mice responded more on the active lever and drank more alcohol in the reinforced condition, but again, there was not an effect of drinking history on this sex-specific effect. Together these results suggest that while female cHAPs, regardless of drinking history, are more motivated to work to drink EtOH, reinforced and non-reinforced instrumental responding are not reliable readouts for tolerance in cHAP mice compared to other endpoints such as drinking in the dark (DID) assays.Item Effect of ketamine on binge drinking patterns in crossed high alcohol-preferring (cHAP) mice(Elsevier, 2021-12) Ardinger, Cherish E.; Winkler, Garrett; Lapish, Christopher C.; Grahame, Nicholas J.; Psychology, School of ScienceBACKGROUND: Previous research has demonstrated the utility of subanesthetic doses of ketamine in decreasing binge (Drinking-in-the-Dark, or DID) 20% alcohol intake in female inbred (C57BL/6J) mice when administered 12 hours prior to alcohol access (Crowley et al., 2019). In the current study, we assess the efficacy of a similar ketamine pretreatment using male and female selectively bred, crossed High Alcohol Preferring (cHAP) mice, which also drink to intoxication, but are not inbred. We hypothesized that ketamine would decrease binge alcohol intake without impacting locomotor activity. METHODS AND RESULTS: Subjects were 28 adult cHAP mice. Mice first received a 2-week DID drinking history using 2-h/day alcohol access. On day 12, prior to ketamine treatment, the average blood ethanol concentration (BEC) was 130 mg/dL, confirming that mice reliably reached intoxicating BECs. On day 15, mice were given 0, 3, or 10 mg/kg of ketamine 12 hours prior to the DID session. Ketamine did not decrease total (2-h) alcohol consumption or locomotion. Interestingly, the 10 mg/kg dose of ketamine did alter the drinking pattern in male mice, decreasing front-loading for a single day. We opted to then increase the doses to 32 or 100 mg/kg (i.e., an anesthetic dose) two days after the initial treatment, keeping the saline control. Mice of both sexes decreased total binge alcohol intake at the 100 mg/kg dose only, but again, the effect only lasted one day. CONCLUSIONS: The current study found that cHAP mice reached more than double the BECs observed in C57BL/6J mice during DID, but did not respond to subanesthetic ketamine. Modest efficacy was found for ketamine pretreatment at anesthetic doses. Differences in findings may be due to differential intake during DID, or genetic differences between C57Bl/6J mice and cHAP mice. Drug efficacy in multiple models is important for discovering reliable pharmacotherapies for alcoholism.