title: Anxiolytic profile of the antiepileptic drug levetiracetam in the Vogel conflict test in the rat.
abstract: The novel antiepileptic drug levetiracetam has been shown to reverse anxiogenic effects of benzodiazepine withdrawal in mice tested in an elevated plus-maze without altering the behaviour of normal mice in this model. This could suggest that the effect of levetiracetam is dependent upon the level of stress/anxiety of the animals. Levetiracetam was therefore further examined in another widely used animal model of anxiety, the Vogel conflict test. In the first experiment, water-deprived rats were submitted to a free drinking period (habituation) in a chamber equipped with a bottle of water. Twenty-four hours later, animals were returned to the same chamber but the licks to the water bottle were then punished with a foot shock (0.5 mA, 90 ms). In the second experiment, the procedure was modified by administering a foot shock at the end of the habituation period in order to induce a state of stress/anxiety (conditioned fear/ anticipatory anxiety) for subsequent testing. Levetiracetam (17 and 54 mg/kg) and chlordiazepoxide (5 mg/kg) were administered via the intraperitoneal route. The results indicated that in the first experiment only chlordiazepoxide showed a statistically significant anxiolytic effect. In contrast, in the second experiment, where the shock was given at the end of the habituation period, levetiracetam (54 mg/kg) revealed significant anxiolytic activity similar to chlordiazepoxide. This suggests that levetiracetam may have potential anxiolytic effects and may provide therapeutic benefits to individual with anxiety spectrum disorders.
authors.affiliation: UCB S.A. Pharma Sector, Preclinical CNS Research, Chemin du Foriest, B-1420 Braine l'Alleud, Belgium. yves.lamberty@ucb-group.com
authors.forename: Yves
authors.initials: Y
authors.lastname: Lamberty
authors.forename: Ursula
authors.initials: U
authors.lastname: Falter
authors.forename: Alma J
authors.initials: AJ
authors.lastname: Gower
authors.forename: Henrik
authors.initials: H
authors.lastname: Klitgaard
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D003220:Conflict, Psychological; D004558:Electric Stimulation / Q000379:methods; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam