Levetiracetam results in increased and decreased alcohol drinking with different access procedures in C57BL/6J mice

Abstract

The antiepileptic, levetiracetam (LEV), has been investigated for the treatment of alcohol abuse. However, little is known about how LEV alters the behavioral effects of alcohol in laboratory animals. The acute effects of LEV on alcohol drinking by male C57BL/6J mice were investigated using two different drinking procedures, limited access (drinking-in-the-dark, or DID) and intermittent access (IA) drinking. In the first experiment (DID), mice had access to a single bottle containing alcohol or sucrose for four hours every-other day. In the second experiment (IA), mice had intermittent access to two bottles, one containing alcohol or sucrose and one containing water, for 24 h on Mon/Wed/Fri. In both experiments, mice were administered LEV (0.3 – 100 mg/kg i.p.) or vehicle 30 min before access to the drinking solutions. In the DID mice, LEV increased alcohol intake from 4.3 to 5.4 g/kg, while in the IA mice LEV decreased alcohol intake from 4.8 to 3.0 g/kg in the first 4 h of access and decreased 24 h alcohol intake from 20 g/kg to approximately 15 g/kg. These effects appear specific to alcohol, as LEV did not affect sucrose intake in either experiment. LEV appears to differentially affect drinking in animal models of moderate and heavier alcohol consumption.

Rodent models and mechanisms of voluntary binge-like ethanol consumption: Examples, opportunities, and strategies for preclinical research

“…Therefore, this enhanced glutamate response appears to reflect ethanol experience-dependent neuroadaptation. Interestingly, the antiepileptic drug levetiracetam, which potently inhibits vesicular release of glutamate (Meehan et al, 2011; Meehan et al, 2012), has been shown to increase ethanol intake in male B6 mice during a 4-hr DID procedure (Fish et al, 2014). In conjunction with the microdialysis data described above, this observation may reflect a compensatory increase in ethanol intake to oppose the drug-induced reduction in glutamatergic tone.…”