Evidence is accumulating for a role of endocannabinoids in epileptic pathophysiology, that cannabinoids are anticonvulsant and may have potential in treatment of epilepsy (Alger, 2004; Wallace et al, 2003). In assessing the role of cannabinoid receptors in the hippocampus (Roe & Mason, 2002) we evaluated the effects of the non-selective CB_1/2 receptor agonist HU-210 on kainate-induced epileptiform discharge activity of rat in vivo.

Multiple extracellular single-unit and local field potential (LFP) activity was recorded from hippocampal CA1 neurones in adult male Sprague-Dawley rats under urethane (1.3g.kg^-1; i.p) anaesthesia. Stereotactically manipulated 8-channel or 16-channel microwire electrode arrays (NB Labs, Texas USA) were used connected to a Plexon Multineurone Acquisition Processor system (Cheer et al, 2003); neural ensemble data was analysed using NeuroEXplorer (Plexon Inc., Texas USA) to examine effects on firing rate and burst firing, with bursts classified using Poisson surprise (S) detection using S>10 (Legendy & Salcman, 1985). The effect of systemic administration of the cannabinoid agonist HU-210 (100 µg.kg^-1; i.p. from a 10mM stock in ethanol) was examined on epileptiform activity induced by kainic acid (10mg.kg^-1; i.p.). Data are presented as mean ± s.e.m. and compared by Student’s paired t-test (Prism version 4; GraphPad, USA).

The basal spontaneous mean firing rate in hippocampal ensembles was 7.7 ± 2.3 Hz (n=98 units/5 rats) which following kainic acid administration resulted in epileptiform activity 21.3 ± 3.5 Hz (p<0.001). This increase in activity was reversed following HU210 to 10.2 ± 2.8 Hz at 40-60 min post CB agonist administration (n=95 units/5rats). These changes in unit activity were mirrored by changes in LFP electrophysiology; administration of vehicle was without effect.

Analysis of hippocampal neuronal bursting activity revealed that kainic acid significantly increased burst rate from spontaneous basal activity of 3.1 ± 1.0 bursts.min^-1 to 8.1 ± 1.5 (p<0.001, n= 98 units/5 rats) and that this was reversed by HU210 administration (2.9 ± 1.2; n=96 units/5rats). Burst duration was altered in a similar fashion with kainic acid increasing duration significantly from 14.8 ± 3.1s to 78.8 ± 7.2s (p< 0.001), an effect reversed by HU210 (3.8 ± 1.3s).

The cannabinoid agonist HU210 reproducibly reversed kainite-induced epileptiform activity in the rat hippocampus and supports the view that cannabinoids may have potential in treatment of epilepsy (Wallace et al, 2003).

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