Geon Forget Me Not: the Role of mGluR5 in Addiction Memory


Addiction to drugs, alcohol or sex is fundamentally a memory disorder: these things are constantly recalled. At the cellular level, it implies that the neurons representing their related events can easily fire. In the past few years, researchers have identified mGluR5 as an addiction molecule (Wang et al., 2013; Schroeder et al., 2008; Li et al., 2013). Pharmaceutical companies are actively developing mGluR5 modulators for the treatment of addiction (Emmitte, 2011).

The Basic Function of mGluR

The glutamate receptors can be divided into two classes: ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). The ionotropic glutamate receptor forms an ion channel such as AMPAR and NMDAR. The mGluR belongs to G-protein-coupled receptors (GPCRs) which use G proteins to mediate signaling cascade.


Figure 6-1. The function of G-protein-coupled receptor. A G protein consists of three subunits: α, β and γ. In the resting state, Gα is bound to a small molecule, guanosine diphosphate (GDP), as well as the other two subunits. Upon activation by the binding between GPCR and its agonist (e.g. mGluR and glutamate), GDP is replaced by GTP (guanosine triphosphate), resulting in the dissociation between the α subunit and the βγ subunits. The dissociated Gα and Gβγ can then act on their effectors, triggering downstream signaling cascade. [Image source: Wikipedia]

mGluR5 and NMDAR

mGluR5 is a subtype of mGluRs. Activation of mGluR5 may either depressing or enhancing synaptic strength, depending on specific signaling pathways. Its normal function is to accelerate extinction for some memories while retaining others longer. For addicts, the memories of drugs, alcohol, gambles or sex are abnormally retained. Their mGluR5 dysfunction appears to enhance synaptic strength by potentiating the response of NMDAR (Pisani et al., 2001; Takagi et al., 2012).


Author: Frank Lee
First Published: April 19, 2013