Selective Breeding for Drinking in the Circadian Dark

Oregon Health & Science University, Portland OR

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): NOT-OD-09-058, NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications. We are producing replicated lines of mice selectively bred for their propensity to high drinking in the dark (HDID). We are breeding mice for their high (>150 mg-%) BALs on the second day of 2 daily exposures to 20% ethanol for 2-4 h/day, starting in hr 3 of their circadian dark cycle. Selection has succeeded, and most mice now drink to intoxication (Crabbe et al. 2009: App MS #2). One aim of the existing grant is to examine the effects on DID of drugs microinfused into INIA-targeted brain circuits, initially the lateral septum and the hippocampus. We have shown in a recent experiment that baclofen/muscimol microinfusions into septum reduced alcohol DID while not affecting water drinking. Alcoholic drinking is characterized bv preoccupation with obtaining access to alcohol (craving) and loss of control over drinking once initiated. These features, termed appetitive and consummatory, respectively, have different biological underpinnings (for an excellent review see (Samson and Hodge. 1996: ADD MS #3). Humans and rodents both tend to drink in focused sessions, or bouts. Thorough description of drinking behavior requires at least consideration of number of bouts, their average inter-bout interval, and the average bout magnitude. The related, homeostaticallv-regulated processes surrounding water intake and feeding behavior must also be studied. Using lickometer-equipped cages, we found that C57BL/6J mice initiated fewer drinking bouts for ethanol. but they ingested ethanol twice as quickly as they did water. No information is available about pattern of food ingestion (lickometer systems cannot do this). We propose to acquire a computerized system (BioDAQ Episodic Intake Monitor cages) that will allow us to assess liquid and food intake with fine temporal resolution during DID sessions. We will be able to assess bout frequency. inter-bout interval, bout duration (size), and whether or not ethanol drinking is temporally coupled with eating (i.e. prandial). Furthermore, we will be able to apply these micro structural behavioral analyses to the response to neurochemicals delivered into the brain. Some human studies suggest that certain patterns of drinking are more susceptible to ameliorative pharmacotherapy than others (Anton et al.. 2004). Thus, different compounds may exert different effects on drinking microstructure. In order to accomplish these additional experiments, we will hire a post-doctoral level person and an additional research assistant, and retain a part-time employee. PUBLIC HEALTH RELEVANCE: This Supplementary project will examine the microstructure of alcohol drinking behavior, its relationship to food and water consumption patterns, and the effects of pharmacological agents microinfused directly into specific brain areas on different aspects of alcohol drinking (e.g., appetitive vs. consummatory). These studies will help further the goals of prediction of risk of alcohol abuse, alcoholism, and specific alcohol-related health problems. The genetic risk and protective markers that we are studying will be of utility in the future for prevention and treatment of alcoholism.