MUNC13-1 heterozygosity does not alter voluntary ethanol consumption or sensitivity in mice

• Published in: Alcohol (Fayetteville, N.Y.) Vol. 83; pp. 89 - 97
• Main Authors: Wooden, Jessica I., Schuller, Kyle, Roman, Gregg, Das, Joydip, Leasure, J. Leigh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2020; Elsevier Limited
• Subjects: Addiction; Alcohol; Alcohol Drinking - genetics; Alcohol use; Animals; Anxiety; Behavior; Binding sites; Cognition; Crosses, Genetic; Drinking behavior; Ethanol; Ethanol - administration & dosage; Female; Genotypes; Heterozygote; Heterozygotes; Insects; Isoforms; Laboratory animals; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morris Water Maze Test; Motor Activity - drug effects; Navigation behavior; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurotransmitters; Proteins; Rodents; Spatial discrimination learning; Spatial learning; Spatial Learning - drug effects; Tolerance; United States > US; Tolerance; Anxiety; Cognition; Addiction; Spatial learning
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2019.06.007

The role of the munc13–1 presynaptic protein in alcohol-related behaviors has been little-studied, despite being a known site of action for ethanol binding. Munc13–1 is an active zone protein that plays a vital role in vesicle maturation and the release of neurotransmitters in excitatory neurons. Ethanol binds munc13–1, which decreases its functionality. In Drosophila, loss of the homologous protein Dunc13 is associated with an increase in ethanol preference, and is associated with a resistance to sedation following ethanol exposure. The current study assessed the effects of munc13-1 heterozygosity on ethanol sensitivity and consumption in mice, as well as on learning and anxiety-like behaviors, which can influence alcohol intake. Wild-type and mutant mice underwent 6 cycles of drinking-in-the-dark (DID) as well as rotarod testing following ethanol injection, to probe for differences in ethanol consumption and sensitivity, respectively. We did not detect genotype-based differences in our measures of anxiety, spatial learning, ethanol consumption, or ethanol sensitivity. However, heterozygotes showed increased use of a spatial navigation strategy in a dual-solution water maze, as opposed to a stimulus-response strategy. To summarize, although reduction of Dunc13 in flies produces clear effects on ethanol consumption and sensitivity, heterozygosity for munc13-1 does not, potentially due to compensatory adaptation by other munc-13 isoforms. •Munc13-1 heterozygosity does not impair spatial navigation or increase anxiety-like behaviors.•Munc13-1 heterozygosity does not increase ethanol consumption in the drinking-in-the-dark paradigm.•Munc13-1 heterozygosity does not influence ethanol intoxication behaviors