Munc 13-1 heterozygosity does not alterVoluntary ethanol consumption or sensitivity in mice.

The role of the munc 13-1 pre-synaptic protein in alcohol-related behaviors has been little-studied, despite being a known site of action for ethanol binding. Munc 13-1 is an active zone protein that plays a vital role in vesicle maturation and the release of neurotransmitter in excitatory neurons. Ethanol binds munc 13-1, decreasing its functionality. In Drosophila, loss of the homologous protein Dunc13 is associated with an increase in ethanol preference, and a resistance to sedation following ethanol exposure. The current study assessed the effects of munc 13-1 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 munc 13-1 does not, potentially due to compensatory adaptation by other munc 13 isoforms.