Brivaracetam does not alter spatial learning and memory in both normal and amygdala-kindled rats.
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 3-30microM 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.
Detrait
E R
ER
UCB Pharma S.A., CNS Research, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium. eric.detrait@ucb.com
Leclercq
K
K
Löscher
W
W
Potschka
H
H
Niespodziany
I
I
Hanon
E
E
Kaminski
R M
RM
Matagne
A
A
Lamberty
Y
Y
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology
D000927:Anticonvulsants; D011760:Pyrrolidinones; C482793:brivaracetam