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Metabotropic glutamate receptor 5 (mGluR5)‐mediated phosphoinositide hydrolysis and NMDA‐potentiating effects are blunted in the striatum of aged rats: a possible additional mechanism in striatal senescence

The aim of the present work was to verify whether an impairment of subtype 5 metabotropic glutamate receptor‐mediated neurotransmission did occur in the aged striatum. To this end, the ability of the subtype 5 metabotropic glutamate receptor agonist, RS‐2‐chloro‐5‐hydroxyphenylglycine, to stimulate phosphoinositide hydrolysis and to potentiate N‐methyl‐d‐aspartate‐induced effects in striatal slices from young (3 months) and aged (24 months) rats was compared. The ability of RS‐2‐chloro‐5‐hydroxyphenylglycine to induce maximal phosphoinositide turnover and to potentiate N‐methyl‐d‐aspartate effects was significantly reduced in slices from old vs. young rats. These changes were associated with a significant reduction in the expression of subtype 5 metabotropic glutamate receptor protein (−28.8%) and phospholipase C‐β1 (−55.8%) in old striata, while receptor messenger ribonucleic acid expression was unchanged. These results show that the signalling associated with subtype 5 metabotropic glutamate receptors undergoes significant age‐related changes and that a reduced expression of subtype 5 metabotropic glutamate receptors and, more importantly, phospholipase C‐β1 may account for the functional decline of subtype 5 metabotropic glutamate receptors.