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-beta1 (-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-beta1 may account for the functional decline of subtype 5 metabotropic glutamate receptors.