Maximal Electroshock Seizure (MES) Test (mouse, rat)

MES is a model for generalized tonic-clonic seizures and provides an indication of a compound’s ability to prevent seizure spread when all neuronal circuits in the brain are maximally active. These seizures are highly reproducible and are electrophysiologically consistent with human seizures. For all MES tests, 60 Hz of alternating current (50 mA in mice and 150 mA in rats) is delivered for 0.2 sec by corneal electrodes. Prior to stimulation corneas are treated with 0.5% tetracaine hydrochloride for local anesthesia and 0.9% saline to improve electrical conductivity. The behavioral seizures are characterized by tonic extension of forelimbs and hindlimbs that is followed by brief episodes of clonic activity of the forelimbs and hindlimbs. An animal is considered “protected” from MES-induced seizures upon abolition of the hindlimb tonic extensor component of the seizure” (White et al., 1995).

Initial qualitative screen for anticonvulsant activity in the MES is performed with N = 4 male CF-1 or C57BL/6 mice or Sprague-Dawley CD albino rats/dose/time point. Three doses and two timepoints based on supporting data are selected to examine the efficacy of the test compound. Quantification of the effective dose that confers protection in 50% of animals treated with the compound (ED50) is conducted at the time of peak effect (TPE) and is described separately.