Neuroscience and Neurobiology
Concise Abstract of the Results of the Work. Our research attempted to understand mechanisms underlying alcohol use and factors that may contribute to alcohol use disorder (AUD). More specifically, the present series of experiments, phases 1 through 4, expand on rodent models research to study binge-like ethanol consumption using the “Drinking In the Dark” (DID) procedure (see Thiele &Navarro, 2014 for a review). In DID, ethanol (EtOH) is provided in the home cage for 3 hours, beginning 3 hours after the start of the dark phase of the light:dark cycle when nocturnal rodents are most active (adapted from Rhodes et al., 2005). Few studies have explored the use of DID to study ethanol consumption in genetically heterogenous outbred rats. Phase 1 of the research attempted to determine whether binge-like ethanol consumption (20% EtOH, 28 days) may be observed in two genetically heterogenous rat lines used in alcohol drinking research (i.e., Sprague-Dawley - SD, and Long Evans - LE). Additionally, the impact of naltrexone (1 mg/kg), an opiate antagonist, on ethanol drinking was assessed across 6 additional days at the end of phase 1. Phase 2 evaluated the impact of an abstinence period, inserted after completion of phase 1, on subsequent ethanol consumption and provided an opportunity to evaluate abstinence induced drinking across the strains (see Simms et al., 2008). This was accomplished by allowing animals to consume 20% EtOH for 5 consecutive days after a 60-day abstinence period. Phase 3 commenced after a 2-day abstinence period and animals consumed 10% EtOH for 5 consecutive days following phase 2. Prospectively, positive behavioralcontrast may be observed, and animals may consume greater quantities of 10% EtOH having consumed less palatable 20% EtOH. Finally, phase 4 attempted to explore whether strain differences may be observed in consumption of 10% EtOH sweetened with “supersac” solution. Super sac (3% glucose w/v, 0.125% saccharine w/v) added to 10% EtOH may encourage bingelike drinking in outbred rats and may be a valid animal model of ethanol consumption given humans typically consume sweetened ethanol beverages(Ji et al, 2008). Phase 4 began after a 23-day abstinence period and followed the same DID procedure used in phases 1-3. The last phase continued for 10 days with 2 separate brief abstinence periods inserted between drinking days. The first was a 2-day abstinence period between days 4 and 5, and the second was a 4-day abstinence period inserted between day 9 and 10. Phase 1 outcomes indicated that LE strain achieved higher doses of EtOH compared to SD strain but did not attain binge-like criteria (1.5 g/kg EtOH) within the initial 30-minute drinking period. Importantly, naltrexone did suppress consumption of EtOH leading to lower doses attained especially so in the LE strain. Phase 2 results showed no initial increase in consumption following an abstinence period and LE achieved higher doses of EtOH. During phase 3, abstinence induced drinking was not observed although LE animals achieved higher doses of EtOH consumed. Interestingly, phase 4 analyses indicated that both strains consumed ethanol in a manner to achieve higher doses especially so in the LE strain. Within phase 4, abstinence induced drinking was observed in the LE strain following the initial 2- day abstinence period, and similar abstinence induced drinking was observed especially so in the LE strain following a 4-day abstinence period inserted between days 9 and 10 of phase 4. Overall, the DID paradigm produced binge drinking in outbred rats, most notably LE strain, when 10% ethanol solution was sweetened with supersac, especially after a brief period of abstinence from drinking. Additionally, naltrexone significantly decreased ethanol consumption, supporting its continued use as a treatment for AUD. Across the 4 Phases, LE rats consistently consumed higher amounts of ethanol, suggesting that they serve as a better outbred rat model for studying ethanol consumption and binge drinking using DID procedures.
Ethanol consumption using the “Drinking In the Dark” (DID) procedure in Sprague Dawley and Long Evans rat lines: Strain comparisons, blood alcohol levels and the impact of naltrexone on alcohol intake
Coste, Sarah, "Bakner and Coste Faculty-Student Summer Collaborative Research Grant: Grant Activities Evaluation Post Grant" (2022). Faculty & Staff Publications. Report. Submission 17.