MAGNESIUM DEFICIENCY-DEPENDENT AUDIOGENIC-SEIZURES (MDDASS) IN ADULT MICE - A NUTRITIONAL MODEL FOR DISCRIMINATORY SCREENING OF ANTICONVULSANT DRUGS AND ORIGINAL ASSESSMENT OF NEUROPROTECTION PROPERTIES

A great many animal models for audiogenic seizures have been described . The extent to which these models may provide insight into neuroscien ce fields such as abnormal locomotor behavior (wild running), seizures and anticonvulsants, and neuroinsults and neuroprotectors is examined here by our study of magnesium deficiency-dependent audiogenic seizur es (MDDASs) in adult mice. MDDASs were induced in all of the eight tes ted adult murine strains and are presented as a sequence of four succe ssive components (latency, wild running, convulsion, and recovery phas e periods). Compared with several classic seizure tests, the nutrition al MDDAS model responded to low doses of prototype antiepileptic drugs (AEDs), including phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), valproic acid (VPA), ethosuximide (ESM), and diazepam (DZP). Mo dulation by AEDs of the four components of MDDAS indicated that this s eizure test was discriminatory, distinguishing between phenytoinergic (PHT, CBZ), GABAergic (PB, VPA, DZP), and ethosuximide (ESM) compounds . Suitability of the MDDAS test for evaluation of neuroprotective comp ounds was also examined: it showed partial (melatonin) and complete (W EB2170, an anti-PAF agent) reduction of recovery phase by non-anticonv ulsant doses of test compounds. These neuroprotective responses were c ompared with neuroprotective potentials determined in a model of neona tal cerebral injury induced by focal injection of ibotenate (a glutama te analog). WEB2170 and melatonin reduced the size of lesions in white matter, but only WEB2170 protected cortical plate against ibotenate-i nduced lesions. In addition to the original neuroprotective behavior o f WEB2170, studies on the neuroprotectors also supported GABAergic ant iconvulsant activity of melatonin in the MDDAS test.