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Effects of URB597 on kainate-evoked epileptiform unit and local field potential (LFP) activity in rat hippocampus Cannabinoids exhibit anticonvulsant properties in animal models of epilepsy (Wallace et al., 2003), while endocannabinoids have been shown to exhibit neuroprotective effects ( Marsicano et al., 2003) . The effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on hippocampal LFP activity was examined to evaluate the role of endocannabinoids in a rat model of kainate (KA)-induced temporal lobe epilepsy. Multi-channel electrode arrays with a PlexonMAP system were used to record extracellular LFPs simultaneously with single-unit spike activity from hippocampus and medial prefrontal cortex of isoflurane-anaesthetised male Lister hooded rats (200-300g). Data were analysed using NeuroExplorer and Matlab comparing basal activity with that observed 60 min post-KA administration. Epileptiform-like activity was evoked using kainic acid (KA;10mg kg-1, i.p.) or KA simultaneously with URB597 (1 mg kg-1, i.p.; dissolved in 5% EtOH / 5% Cremophor EL / 90% saline, v/v %). KA reduced the proportion of LFP power in the delta-band while increasing that seen in the higher frequency bands. URB597 did not appear to alter these KA-evoked effects on LFP activity. However, URB597 blocked the KA-induced increase in unit firing rate by >90% (P<0.01; 2-way ANOVA; n = 68 cells, 5 rats).
Fig 1: Distribution (% total LFP energy; mV2; 0-500Hz), in the delta (1-4Hz), theta (4-8Hz), alpha (8-15Hz), beta (15-30Hz) and gamma (30-100Hz) hippocampal LFP frequency bands during basal (white) recording and KA-evoked (black) activity following vehicle or URB597 administration.
URB597-mediated inhibition of endocannabinoid metabolism appears to reduce the severity of epileptiform-like activity in this acute seizure model by targeting unit spiking activity within temporal lobe structures.
Marsicano et al. (2003). Science 302: 84-88. |
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