Brivaracetam does not alter spatial learning and memory in both normal and amygdala-kindled rats

Detrait, E.R.; Leclercq, K.; Löscher, W.; Potschka, H.; Niespodziany, I.; Hanon, E.; Kaminski, R.M.; Matagne, A.; Lamberty, Y.

doi:10.1016/j.eplepsyres.2010.06.014

« Previous Next »Epilepsy Research
Volume 91, Issue 1 , Pages 74-83, September 2010

Brivaracetam does not alter spatial learning and memory in both normal and amygdala-kindled rats

E.R. Detrait
- UCB Pharma S.A., CNS Research, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium
- Corresponding author at: UCB Pharma S.A., CNS Research - In vivo Pharmacology Dpt, R9 Building, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium. Tel.: +32 2 386 6196; fax: +32 02 386 3141.
K. Leclercq
- UCB Pharma S.A., CNS Research, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium
W. Löscher
- Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Bünteweg 17, 30559 Hannover, Germany
H. Potschka
- Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, and Center for Systems Neuroscience, Bünteweg 17, 30559 Hannover, Germany
I. Niespodziany
- UCB Pharma S.A., CNS Research, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium
E. Hanon
- UCB Pharma S.A., CNS Research, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium
R.M. Kaminski
- UCB Pharma S.A., CNS Research, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium
A. Matagne
- UCB Pharma S.A., CNS Research, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium
Y. Lamberty
- UCB Pharma S.A., CNS Research, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium

Received 26 February 2010; received in revised form 25 June 2010; accepted 29 June 2010.

Summary

Several antiepileptic drugs (AEDs) may induce memory deficits when tested in preclinical models at doses that exert significant protection against seizures. Brivaracetam (BRV) is a novel high-affinity SV2A ligand also displaying inhibitory activity at neuronal voltage-gated sodium channels. In the present study we have investigated the effects of BRV, at doses that exerted marked anticonvulsant effects in kindled rats, upon cognitive functioning and memory in both normal and amygdala-kindled rats using place learning version of Morris water maze. In addition the effect of BRV on long-term potentiation (LTP) in rat hippocampal slices has been investigated.

BRV (2.1, 6.8 or 21.0mg/kg i.p.) was injected daily, 60min before each session. Results indicated that in both normal and amygdala-kindled rats BRV did not alter the latency to find the hidden platform or swimming speed during the four consecutive days of learning. Similarly, the time spent in the target quadrant, used as a further independent index of spatial memory, was not modified by BRV treatment. Likewise, BRV did not affect the LTP induction in CA1 hippocampal region when tested at 3–30μM concentration range, which had been demonstrated to significantly reduce epileptiform activity in slice models.

Based on the results of the present study it can be expected that BRV will not have detrimental effects on hippocampal-dependent cognitive functions in patients with epilepsy.

Keywords: Brivaracetam, Morris water-maze, Spatial memory, Cognitive function, Long-term potentiation, Amygdala kindling, Antiepileptic drugs