The role of mGlu receptors in susceptibility to stress-induced anhedonia, fear, and anxiety-like behavior

Examining mGlu5 Receptor Availability as a Predictor of Vulnerability to PTSD: An [18F]FPEB and PET Study in Male and Female Rats

“…Specifically, regardless of sex, lower receptor availability in AMY and higher receptor availability in HIP, PFC, and STR was observed in rats that would go on to be SEFL(+) relative to those that would be SEFL(−). These findings add to the growing preclinical evidence implicating differences in mGlu5 receptor expression and activity contributing to susceptibility or resilience in rodent models of stress and fear learning, 8,17,[35][36][37] and likewise are consistent with clinical neuroimaging studies from our lab 12,13 where corticolimbic mGlu5 receptor availability was higher in individuals with PTSD relative to individuals with major depressive disorder and healthy controls. Collectively, these data support the hypothesis that higher mGlu5 availability could indeed represent a molecular "biomarker" for PTSD vulnerability and novel treatment target.…”

“…In recent years, the metabotropic glutamate receptor 5 (mGlu5) has gained attention as a potential biomarker and molecular mediator of PTSD susceptibility. 8,9 This Gq/11 protein-coupled receptor mediates forms of synaptic plasticity underpinning hippocampal-dependent memory, and particularly, affective learning processes. [9][10][11] Further, there is mounting evidence from human postmortem investigations and clinical neuroimaging studies that suggest dysregulation of the mGlu5 receptor in PTSD.…”

Design, Synthesis, Pharmacology, and In Silico Studies of (1S,2S,3S)-2-((S)-Amino(carboxy)methyl)-3-(carboxymethyl)cyclopropane-1-carboxylic Acid (LBG30300): A Picomolar Potency Subtype-Selective mGlu2 Receptor Agonist

“…Group I (mGlu 1,5 ) are foremost located post-synaptically and excitatory in action by coupling to Gq proteins, leading to activation of the phospholipase C (PLC) pathway, whereas group II (mGlu 2,3 ) and group III (mGlu 4,6,7,8 ) are foremost expressed presynaptically and are inhibitory in action, by coupling to Gi/o proteins, which leads to inhibition of adenylyl cyclase (AC). , Group II subtypes mGlu 2 and mGlu 3 are differentially distributed in the CNS and exert distinct functions . While mGlu 2,3 are localized pre- and postsynaptically in neurons, mGlu 3 is also found in glial cells. − Extensive pharmacological studies suggest that mGlu 2 and mGlu 3 are associated with several neurological and psychiatric disorders such as cognitive impairment and drug addiction. − …”