Long-term disease-modifying effect of the endocannabinoid agonist WIN55,212-2 in a rat model of audiogenic epilepsy.
BACKGROUND
Modulation of the endocannabinoid (eCB) transmission is a promising approach to treating epilepsy. Animal models can be used to investigate this approach. Krushinsky-Molodkina (KM) rats have, genetically, audiogenic epilepsy. Moreover, in these animals, repeated induction of audiogenic seizures results in a progressive prolongation of the seizures, known as audiogenic kindling.


METHODS
The present study evaluated, in these KM rats, acute and long-term effects of a single dose of 4 mg/kg of the cannabinoid-receptor agonist WIN55,212-2.


RESULTS
Administration of the single dose of WIN55,212-2 one hour before the 4th seizure delayed the kindling process by two weeks, without any acute effect on the audiogenic seizures.


CONCLUSIONS
This result suggests that short-term potentiation of the eCB system might modify the epileptogenic disease process in patients with a progressive course of epilepsy.
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia. Electronic address: lvinogradova@gmail.com.
Lyudmila V
LV
Vinogradova
Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, The Netherlands. Electronic address: t.vanrijn@donders.ru.nl.
Clementina M
CM
van Rijn
D000161:Acoustic Stimulation / Q000009:adverse effects* / Q000379:methods; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology / Q000627:therapeutic use*; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000819:agonists*; D020195:Epilepsy, Reflex / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D013997:Time Factors; D016896:Treatment Outcome
D048588:Benzoxazines; D002186:Cannabinoids; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
Audiogenic seizures; Endocannabinoid; Epileptogenesis; Kindling; WIN55,212-2