Ethanol-associated behaviors of mice lacking norepinephrine

Although norepinephrine (NE) has been implicated in animal models of ethano l consumption for many years, the exact nature of its influence is not clea r. Lesioning and pharmacological studies examining the role of NE in ethano l consumption have yielded conflicting results. We took a genetic approach to determine the effect of NE depletion on ethanol-mediated behaviors by us ing dopamine beta-hydroxylase knockout (Dbh-/-) mice that specifically lack the ability to synthesize NE. Dbh-/- males have reduced ethanol preference in a two-bottle choice paradigm and show a delay in extinguishing an ethan ol-conditioned taste aversion, suggesting that they drink less ethanol in p art because they find its effects more aversive. Both male and female Dbh-/ - mice are hypersensitive to the sedative and hypothermic effects of system ic ethanol administration, and the sedation phenotype can be rescued pharma cologically by acute replacement of central NE. Neither the decreased body temperature nor changes in ethanol metabolism can explain the differences i n consumption and sedation. These results demonstrate a significant role fo r NE in modulating ethanol-related behaviors and physiological responses.