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Review
. 2015 Mar 18:9:86.
doi: 10.3389/fnins.2015.00086. eCollection 2015.

The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction: combining preclinical evidence with human Positron Emission Tomography (PET) studies

Sylvia Terbeck  1 , Funda Akkus  2 , Laurence P Chesterman  3 , Gregor Hasler  2
Affiliations
Review

The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction: combining preclinical evidence with human Positron Emission Tomography (PET) studies

Sylvia Terbeck et al. Front Neurosci. .

Abstract

In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET) and combined the findings with preclinical animal research. This combined view of different methodological approaches-from basic neurobiological approaches to human studies-might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC). Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays an important role in systems for social functioning and the response to social stress. Finally, mGluR5's important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoC's arousal and modulatory systems domain. Glutamate was previously mostly investigated in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.

Keywords: PET; addiction; anxiety; mGluR5; mood disorders.

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Figures

Figure 1
Figure 1
Localization of mGluR5 mRNA in the adult and the 6-day-old rat brains by in situ hybridization. Negative film images of sagittal section of the adult rat brain (A) and the 6-day-old rat brain (B) are shown. OB, main olfactory nucleus; Ac, accumbens nucleus; Tu, olfactory tubercle; St, striatum; Hi, hippocampus; S, subiculum; Cx, cerebral cortex; LS, lateral septal nucleus; IC, inferior colliculus; Cb, cerebellar cortex; Sp, spinal trigeminal nucleus; T, thalamus; VMH, ventromedial hypothalamic nucleus. Scale bar, 4 mm. From Abe et al. (1992). Note: the figure and its legend is reproduced with permission.
Figure 2
Figure 2
Image display the average brain uptake of mGluR5 DVR in the three diagnostic groups. The brain uptake is visible reduced in smoker and ex-smokers groups. Images are calculated by PMOD software version 3 (PMOD Technologies). From Akkus et al. (2013). Note: the figure and its legend is reproduced with permission.
Figure 3
Figure 3
mGluR5 involvement in addiction.
Figure 4
Figure 4
Summary of mGluR5 mechanisms.
See this image and copyright information in PMC

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