Modulation of anticonvulsant effects of cannabinoid compounds by GABA-A receptor agonist in acute pentylenetetrazole model of seizure in rat |
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Authors: | Naderi Nima Ahmad-Molaei Leila Aziz Ahari Farzad Motamedi Fereshteh |
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Institution: | (1) Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran |
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Abstract: | Cannabinoid system plays an important role in controlling neuronal excitability and brain function. On the other hand, modulation
of gamma-aminobutyric acid (GABA) transmission is one of the initial strategies for the treatment of seizure. The aim of the
present study was to evaluate possible interaction between cannabinoidergic and GABAergic systems in pentylenetetrazole (PTZ)-induced
acute seizure in rat. Drugs were administered by intracerebroventricular (i.c.v.) administration 20 min before a single intraperitoneal
(i.p.) injection of PTZ and the latency to the first generalized tonic-clonic seizure was measured. Both the cannabinoid receptor
agonist WIN55212-2 (10, 30, 50 and 100 μg/rat) and the GABA-A receptor agonist isoguvacine (IGN; 10, 30 and 50 μg/rat) significantly
increased the latency of seizure occurrence. Moreover, the fatty acid amide hydrolase inhibitor URB597 showed no anticonvulsive
effect while the monoacyl glycerol lipase (MAGL) inhibitor URB602 (10, 50 and 100 μg/rat) protected rats against PTZ-induced
seizure. Moreover, co-administration of IGN and cannabinoid compounds attenuated the anticonvulsant action of both WIN55212-2
and IGN in this model of seizure. Our data suggests that exogenous cannabinoid WIN55212-2 and MAGL inhibitor URB602 imply
their antiseizure action in part through common brain receptorial system. Moreover, the antagonistic interaction of cannabinoids
and IGN in protection against PTZ-induced seizure could suggest the involvement of GABAergic system in their anticonvulsant
action. |
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Keywords: | |
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