Specific group II metabotropic glutamate receptor activation inhibits the development of kindled epilepsy in rats

The effects of intracerebral administration of the group II metabotropic glutamate receptor agonist, 2R,4R-APDC, were tested on both the development of amygdaloid kindling and on fully developed stage 5 amygdala kindled seizures. The development of amygdaloid kindling was significantly retarded in 2R,4R-APDC (10 nmol in 0.5 mu l) treated animals compared to control animals over a period of 8 days. At a low dose, 2R,4R-APDC (0.1 nmol) caused a 42.5 +/- 26.6% increase of the generalised seizure threshold in fully kindled animals. As higher doses were administered, however, the changes in generalised seizure threshold were less marked, and even a small decrease in the threshold was seen (-19.6 +/- 5.36% at 10 nmol). The agonist 2R,4R-APDC inhibited depolarization-induced release of [H-3]D-aspartate from cortical synaptosomes with an IC50 value of 0.29 mu M. This effect was maximal at 1 mu M, and decreased with dose thereafter. These findings suggest that the selective activation of the group II metabotropic glutamate receptors by agonists such as 2R,4R-APDC may be of therapeutic potential in the treatment of seizure disorders. (C) 1998 Elsevier Science B.V.