mGlu5 receptors | Ricerc@Sapienza

Pharmacological activation of mGlu5 receptors with the positive allosteric modulator VU0360172, modulates thalamic GABAergic transmission

Previous studies have shown that injection of the mGlu5 receptor positive allosteric modulator (PAM)
VU0360172 into either the thalamus or somatosensory cortex markedly reduces the frequency of spike-and-wave
discharges (SWDs) in the WAG/Rij model of absence epilepsy. Here we have investigated the effects of
VU0360172 on GABA transport in the thalamus and somatosensory cortex, as possible modes of action underlying
the suppression of SWDs. Systemic VU0360172 injections increase GABA uptake in thalamic synaptosomes

In vivo non-radioactive assessment of mGlu5 receptor-activated polyphosphoinositide hydrolysis in response to systemic administration of a positive allosteric modulator.

mGlu5 receptor-mediated polyphosphoinositide (PI) hydrolysis is classically measured
by determining the amount of radioactivity incorporated in inositolmonophosphate
(InsP) after labeling of membrane phospholipids with radioactive inositol. Although this
method is historically linked to the study of mGlu receptors, it is inappropriate for the
assessment of mGlu5 receptor signaling in vivo. Using a new ELISA kit we showed
that systemic treatment with the selective positive allosteric modulator (PAM) of mGlu5