Methohexitone antagonises kainate and epileptiform activity in rat neocortical slices

Using a grease-seal technique on cortical slices, methohexitone (10-316 microM) dose dependently and reversibly reduced depolarising responses to kainate more than those to alpha-amino-3-hydroxy-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA). The respective pA2 values were 4.9 +/- 0.07, 3.6 +/- 0.03 and 4.0 +/- 0.05 whereas, for 6-nitro,7-sulphamoylbenz[F]quinoxalinedione (NBQX), they were 5.8 +/- 0.06, 6.7 +/- 0.05 and < 4.0. Methohexitone was also more effective than NBQX in reducing the spontaneous epileptiform activity occurring in these cortical slices. Thus 10 and 20 microM of this short-acting barbiturate reduced afterpotentials and burst frequencies respectively by about 50% whereas NBQX 10 microM only reduced burst frequency by some 15%. The results are discussed with respect to a putative methohexitone- and kainate-sensitive autoreceptor which facilitates presynaptic glutamate release.