TY  - JOUR
A1  - Perescis, Martin F. J.
A1  - Bruin, Natasja de
A1  - Heijink, Liesbeth
A1  - Kruse, Chris
A1  - Vinogradova, Lyudmila
A1  - Lüttjohann, Annika
A1  - Luijtelaar, Gilles van
A1  - Rijn, Clementina M. van
T1  - Cannabinoid antagonist SLV326 induces convulsive seizures and changes in the interictal EEG in rats
T2  - PLoS one
N2  - Cannabinoid CB1 antagonists have been investigated for possible treatment of e.g. obesity-related disorders. However, clinical application was halted due to their symptoms of anxiety and depression. In addition to these adverse effects, we have shown earlier that chronic treatment with the CB1 antagonist rimonabant may induce EEG-confirmed convulsive seizures. In a regulatory repeat-dose toxicity study violent episodes of “muscle spasms” were observed in Wistar rats, daily dosed with the CB1 receptor antagonist SLV326 during 5 months. The aim of the present follow-up study was to investigate whether these violent movements were of an epileptic origin. In selected SLV326-treated and control animals, EEG and behavior were monitored for 24 hours. 25% of SLV326 treated animals showed 1 to 21 EEG-confirmed generalized convulsive seizures, whereas controls were seizure-free. The behavioral seizures were typical for a limbic origin. Moreover, interictal spikes were found in 38% of treated animals. The frequency spectrum of the interictal EEG of the treated rats showed a lower theta peak frequency, as well as lower gamma power compared to the controls. These frequency changes were state-dependent: they were only found during high locomotor activity. It is concluded that long term blockade of the endogenous cannabinoid system can provoke limbic seizures in otherwise healthy rats. Additionally, SLV326 alters the frequency spectrum of the EEG when rats are highly active, suggesting effects on complex behavior and cognition.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/42890
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-428907
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289424
SN  - 1932-6203
N1  - Copyright: © 2017 Perescis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 12
IS  - (2): e0165363
SP  - 1
EP  - 16
PB  - PLoS
CY  - Lawrence, Kan.
ER  -