Anxiolytic effects of the novel anti-epileptic drug levetiracetam in the elevated plus-maze test in the rat.

There is clinical evidence of anxiolytic action of several anti-epileptic drugs. We evaluated the effects of levetiracetam (Keppra), a new generation anti-epileptic drug, in the plus-maze animal test for anxiolytic activity. Levetiracetam at 17 and 54 mg/kg intraperitoneally (i.p.) was without effect when tested in naive rats. A modified version of the test was subsequently used in which open-arm exploration was decreased by exposure of the rats to a four-open-arm maze 24 h prior to drug treatment and testing. Under these conditions of enhanced anxiety, levetiracetam, 5.4 to 54 mg/kg, dose-dependently increased open-arm exploration. Chlordiazepoxide 5 mg/kg had similar effects although buspirone 0.1 to 1.0 mg/kg was inactive. The results with levetiracetam substantiate similar findings of its anxiolytic actions against chlordiazepoxide withdrawal-induced anxiety in mice and in a modified Vogel test in rats and support a potential clinical use of this drug in anxiety states.