Protective effects of the CB1 receptor agonist WIN 55.212-2 during development of seizure activity in the brain in models of temporal epilepsy in vivo

The effects of intracerebral intraventricular administration of the nonselective cannabinoid CB1 receptor WIN 55.212-2 (1 μM, 2 μl) on seizure activity were studied in conscious guinea pigs. Changes in local field potential and convulsive discharges evoked by electrical stimulation of the perforant path were recorded simultaneously in the hippocampus, entorhinal cortex, medial septal area, and amygdala after prior administration of WIN 55.212-2 or the organic solvent DMSO. In 80% of tests, WIN 55.212-2 was found to block the development of seizure activity. Repeated injections of agonist for 30 days increased the amplitude of local field potentials and the power of the theta rhythm in all structures recorded. Administration of kainic acid provoked status epilepticus in control animals, while status epilepticus did not arise in guinea pigs given daily agonist injections for 25–30 days. The possible mechanisms of the protective effects of WIN 55.212-2 are discussed.