KINDLED SEIZURES INCREASE METABOTROPIC GLUTAMATE-RECEPTOR EXPRESSION AND FUNCTION IN THE RAT SUPRAOPTIC NUCLEUS

The spread of experimentally kindled seizures in rats results in susta ined increases in plasma vasopressin (VP) and VP mRNA in the supraopti c nucleus (SON), These increases provide an excellent example of the p athological plasticity that can develop in normal cells exposed to rec urrent seizure activity, To test whether this plasticity might be due in part to changes in metabotropic glutamate receptors (mGluRs), we ex amined mGluR mRNA expression in the SON 1 month after stage 5 amygdala kindling. Three mGluR subtypes were detected by in situ hybridization in the SON in the following relative levels: mGluR3 > mGluR1 > mGluR7 , Both mGluR1 and mGluR3 mRNAs were significantly increased in the SON (+28-61%) and cortex (+27-42%) after kindling. Immunoreactivity for m GluR1 but not mGluR2/3 was significantly increased in vivo in the SON. Receptor protein expression and intracellular calcium accumulation in response to the mGluR agonist, 1S,3R ACPD, were evaluated after in vi tro ''kindling'' of neuroendocrine cells by Mg2+ deprivation, Increase d immunoreactivity for mGluR1 and mGluR2/3 was seen in all cultures 3 days after a brief exposure to Mg2+-free medium. 1S,3R 1-aminocyclopen tane-1,3-dicarboxylic acid (ACPD) induced rapid peak responses and gra dual accumulations of intracellular Ca2+ in neurons. Both responses we re increased in the ''kindled'' cells. Increases in the expression of functional mGluR1 and perhaps mGluR3 receptors may contribute to the d evelopment of long-lasting plastic changes associated with seizure act ivity. (C) 1998 Wiley-Liss, Inc.