ALTERED EXPRESSION OF GROUP-I METABOTROPIC GLUTAMATE RECEPTORS IN THEHIPPOCAMPUS OF AMYGDALA-KINDLED RATS

Kindling is a well documented model of acquired focal epilepsy and syn aptic plasticity in the nervous system. Previous biochemical studies h ave indicated an increase in mGluR-mediated phosphoinositide hydrolysi s in the amygdala or hippocampus of fully kindled animals. In this stu dy we have used in situ hybridisation techniques to examine the mRNA e xpression of group I metabotropic glutamate receptors (mGluR1 and mGlu R5 both linked to phosphoinositide hydrolysis) in the hippocampus of a mygdala-kindled animals sacrificed 24 h, 7 days or 28 days following t he last electrically evoked stage 5 seizure, and in implanted non-stim ulated control rats. Results indicate an initial up-regulation in mGlu R1 mRNA (expressed as percentage of control) bilaterally in the DG (35 -40%) and CA3 (16-48%), and unilaterally in CA4 (12%) in the 24 h post -kindled group. In kindled animals studied 7 days after the last seizu re, these changes were either reduced or had returned to control level s. By 28 days mGluR1 mRNA levels had returned to control levels, with only a persistent increase in expression unilaterally in the DG (14%). In contrast, an initial down-regulation in mGluR5 mRNA was observed b ilaterally in CA4 (-45 and -25%) and CAI (-46 and -45%), and unilatera lly in DG and CA3 (-27 and -42% respectively) 24 h after the last kind led seizure. In the 7 and 28 day kindled groups significant alteration s in expression of mGluR5 mRNA were still apparent. These data show th at the mRNAs for mGluR1 and mGluR5 are differentially regulated by kin dling, indicating that the expression of each of these receptors is un der independent regulatory control. These perturbations in mRNA expres sion may contribute to kindling epileptogenesis but are unlikely to ac count for the maintenance of the kindled state.