ANTICONVULSIVE AND NEUROPROTECTIVE ACTIONS OF A POTENT AGONIST (DCG-IV) FOR GROUP-II METABOTROPIC GLUTAMATE RECEPTORS AGAINST INTRAVENTRICULAR KAINATE IN THE RAT

Anticonvulsive and neuroprotective effects of (2S,1'R,2'R,3'R)-2-(2,3- dicarboxycyclopropyl) glycine (DCG-IV), a potent agonist for Group II metabotropic glutamate receptors, were examined in vivo against the ex citotoxicity of kainic acid in the rat. Intraventricular injection of kainic acid (2 nmol) induced circling behavior and wet-dog shakes soon after injection, followed by episodes of limbic motor seizures at int ervals of several minutes (sporadic limbic motor seizures). The freque ncy of sporadic limbic motor seizures gradually increased until seizur es occurred incessantly (continuous limbic motor seizures). Intraventr icular kainic acid also caused severe selective neuron damage in the h ippocampal CA3 region, limbic lobe and medial geniculate body. Prolong ed intraventricular infusion of DCG-IV (24-240 pmol/h) for 17 h before and 7 h after the application of kainic acid decreased the incidence of the continuous limbic motor seizures and the degree of neuronal dam age in circumscribed brain areas. However, the behavioral changes obse rved immediately after the administration of kainic acid mere unaffect ed by prolonged intraventricular infusion with DCG-IV (8-2400 pmol/h). Similarly, the occurrence of sporadic limbic motor seizures was only slightly reduced by the administration of DCG-IV (8-800 pmol/h). High doses of DCG-IV, greater than 800 pmol/h, afforded no protection again st kainate-induced lesions; rather, the degradation of hippocampal CAI pyramidal neurons was increased under such conditions. Single injecti ons of DCG-IV (10-300 pmol/rat) in the lateral ventricle did not affec t kainate neurotoxicity. Thus, prolonged infusion of DCG-IV showed a b ell-shaped dose-response relationship with regard to protection agains t kainate-induced neurotoxicity. Copyright (C) 1997 IBRO.