Mechanisms underlying tolerance to and dependence on the anticonvulsant effect of clonazepam are not clear. Autoradiography of the NMDA receptors in amygdala-kindled rats with tolerance to and dependence on the anticonvulsant effect of clonazepam was carried out. When tolerance developed, the binding of [3H] TCP (N-(1-thieny) cyclohexylpiperidine) to NMDA receptors was found to be increased at the polymorphocellular layer of the right CA1, and decreased at the molecular layer of the cerebellar ansiform lobule. On day 7 of the discontinuation of clonazepam, the binding did not change further. These changes may be responsible for the tolerance to and dependence on the anticonvulsant effect of clonazepam. However, the exact significance of these results should be further investigated.
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