Long-lasting enhancement of metabotropic excitatory amino acid receptor-mediated polyphosphoinositide hydrolysis in the amygdala/ pyriform cortex of deep prepiriform cortical kindled rats

Abstract

We have previously demonstrated that ibotenate (IBO)-stimulated polyphosphoinositide (PPI) hydrolysis is increased for a long period in the amygdala/pyriform cortex (AM/PC) of amygdala (AM)- and hippocampal (HIPP)-kindled rats 1,2,37. This finding indicates that enhanced function of the PPI-coupled excitatory amino acid (EAA) receptor may be associated with the long-lasting seizure susceptibility of kindling. The present study further examined PPI hydrolysis induced by trans-ACPD, a selective agonist of the metabotropic EAA receptor, as well as by IBO in brain slices of rats kindled from the deep prepiriform cortex (DPC). IBO-stimulated accumulation of [ 3H]inositol monophosphate ([ 3H]InsP) was significantly increased in the AM/PC by 162 ( P < 0.0001), 130 ( P < 0.005) and 81% ( P < 0.03) at 24 h, 7 days and 28 days, respectively, after the last kindled seizure, whereas it was increased significantly only at 24 h after the last seizure in the HIPP and did not change at any time in the limbic forebrain (LFB). The IBO-stimulated accumulation of [ 3H]InsP was significantly increased by 55% ( P < 0.01) in the AM/PC of partially kindled rats reaching an average stage of 3.7, but not in the AM/PC of those remaining at stage 1,7 days after the last kindled seizure. Trans-ACPD-stimulated PPI hydrolysis was significantly increased in the AM/PC of DPC-kindled rats by 65 ( P < 0.05) and 45% ( P < 0.005) at 7 and 28 days, respectively, after the last kindled seizure. Cis-ACPD-stimulated PPI hydrolysis was also significantly increased in the AM/PC of DPC-kindled rats by 45 ( P < 0.03) and 30% ( P < 0.04) at 7 and 28 days, respectively, after the last seizure. There was no increase in trans-ACPD- or cis-ACPD-stimulated PPI hydrolysis in the HIPP or LFB. These results further confirm our previous studies showing that the metabotropic EAA receptor-stimulated PPI hydrolysis exhibited a long-lasting increase in the AM/PC irrespective of the primary stimulation site for kindling.