Metabotropic glutamate receptors in the hippocampus and nucleus accumbens are involved in generating seizure-induced hippocampal gamma waves and behavioral hyperactivity.

摘要

The involvement of metabotropic glutamate receptor (mGluR) subtypes in the generation of hippocampal EEG (30-100 Hz) and behaviors induced by a hippocampal afterdischarge (AD) was examined in freely behaving rats. A hippocampal AD induced an increase in gamma waves (30-100 Hz) for 20 min, accompanied by behavioral hyperactivity. Bilateral intracerebroventricular (i.c.v.) infusion of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, 30 min before a hippocampal AD, significantly suppressed both the increase in gamma waves and the behavioral hyperactivity. The hippocampal theta rhythm, the spontaneous hippocampal gamma waves, and evoked field potential oscillations of approximately 40 Hz were not affected by MCPG. Pre-infusion (i.c.v.) of (2S)-alpha-ethylglutamic acid (EGLU; a group II mGluR antagonist), but not (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; a group I mGluR antagonist), suppressed the postictal increase of both hippocampal gamma waves and behaviors. MCPG was infused locally into different brain structures in order to specify its target sites. Intra-hippocampal infusion of MCPG, or EGLU, blocked the increase in both gamma waves and behaviors. Infusion of MCPG into the nucleus accumbens suppressed the postictal behavioral hyperactivity without affecting the increase in hippocampal gamma waves. MCPG injected into the medial septum blocked neither postictal gamma activity nor behavioral hyperactivity. It is suggested that the group II mGluRs in the hippocampus are involved in generation of the postictal hippocampal gamma waves, while behavioral hyperactivity is partly mediated by mGluRs in the nucleus accumbens. However, spontaneous gamma and theta waves in the normal hippocampus are not mediated by mGluRs.