Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions

John C. Crabbe, Pamela Metten, Lawrence C. Huang, Jason P. Schlumbohm, Stephanie E. Spence, Amanda M. Barkley-Levenson, Deborah A. Finn, Justin S. Rhodes, Andy J. Cameron
2012 Addiction Genetics  
Individual mice differ in the dose of ethanol they will ingest voluntarily when it is offered during limited access periods in the circadian dark, a phenotype called drinking in the dark (DID). Substantial genetic variation in DID has been reported across a few standard inbred mouse strains, and a line of High Drinking in the Dark (HDID) mice has been established through selective breeding on the blood ethanol concentration (BEC) they attain at the end of a drinking session. Here, we report
more » ... Here, we report ethanol DID data for 23 inbred mouse strains, including 11 not previously reported, corroborating the genetic contributions to this trait. We also report data on a different ethanol drinking trait, the increased intake seen after multiple cycles of chronic intermittent exposure to ethanol vapor (CIE). Drinking escalated significantly during ethanol withdrawal. However, HDID mice and their HS controls showed equivalent escalation during withdrawal, demonstrating that withdrawal-associated drinking escalation is not a clear genetic correlate of selection on DID. Across inbred strains, DID is substantially genetically correlated with previously-published twobottle ethanol preference drinking data assessed under conditions of continuous ethanol access. Although inbred strain data for withdrawalassociated drinking are not available, the current pattern of results suggests that withdrawal-associated drinking is genetically distinct from DID, while genetic contributions to DID and two-bottle preference drinking are substantially similar. Keywords Withdrawal • Drinking • Preference • Genetics • Mouse • Selective breeding • Inbred strains • Chronic intermittent exposure • Dependence © Versita Sp. z o.o. and Alcoholism, i.e., a pattern of ingestion leading [humans] to BECs > 80 mg% [5] . We offered mice access to a single bottle of 20% v/v ethanol for a period of 2 hr starting shortly after the onset of their circadian dark period. After 3 days of 2 hr access, we extended access on the 4th day to 4 hr. The high-preferring C57BL/6J inbred mouse strain drank more than 4 g/kg in 4 hr and reached BECs > 100 mg% in this "drinking in the dark" (DID) test [6] . A subsequent survey of 12 inbred strains showed substantial genetic variability in DID as assessed by both intake and BEC [7] . Further establishing a genetic basis for DID, we successfully bred a line of High Drinking in the Dark (HDID-1) mice by mating those animals that reached the highest BECs after DID [8]. Heritability of the DID trait is substantially less than that of two-bottle preference drinking; however, HDID mice drink to higher BECs than C57BL/6J mice [8] . Both genotypes display behavioral signs of intoxication after DID [6] [7] [8] . Another approach that investigators have taken to achieve oral ethanol intakes that lead to intoxication is to establish limited access two-bottle preference for 15% ethanol and then induce a state of physical dependence through chronic intermittent ex-3 Unauthenticated Download Date | 2/26/20 1:02 AM
doi:10.2478/addge-2012-0002 fatcat:rewo6czxaja3xeplpux7db4zhm