Anxiolytic profile of the antiepileptic drug levetiracetam in the Vogel conflict test in the rat.
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.
Lamberty
Yves
Y
UCB S.A. Pharma Sector, Preclinical CNS Research, Chemin du Foriest, B-1420 Braine l'Alleud, Belgium. yves.lamberty@ucb-group.com
Falter
Ursula
U
Gower
Alma J
AJ
Klitgaard
Henrik
H
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
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam