Metabotropic glutamate receptor 5 binding in male patients with alcohol use disorder

Akkus, Funda; Mihov, Yoan Venceslavov; Treyer, V; Ametamey, SM; Johayem, A; Senn, S; Rösner, S; Buck, A; Hasler, Gregor (2018). Metabotropic glutamate receptor 5 binding in male patients with alcohol use disorder. Translational psychiatry, 8(1), p. 17. Nature Publishing Group 10.1038/s41398-017-0066-6

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Glutamate signaling plays a major role in addiction. Preclinical research strongly suggests an implication of G-protein-coupled metabotropic glutamate receptor subtype 5 (mGluR5) in nicotine addiction and alcohol use disorder. In humans, smoking is related to a global reduction in mGluR5 availability. In the present study, we investigated mGluR5 in vivo in patients with alcohol use disorder without the confounding effects of smoking. 14 male subjects with alcohol use disorder and at least a 25 days abstinence and 14 matched male non-smoking healthy controls were included in the study. We employed positron emission tomography (PET) with the mGluR5-specific radiotracer [11C]ABP688, using a bolus/infusion protocol. We found increased mGluR5 DVR in several regions within the temporal lobe in patients, as compared to controls. The largest between group-difference was in the amygdala. There was a marked positive relation between mGluR5 DVR in the anterior cingulate and mGluR5 DVR in the orbitofrontal cortex in patients, but not in controls. In patients, lower temptation to drink was related to higher amygdala mGluR5 DVR. We did not find altered mGluR5 DVR in the basal ganglia of subjects recovering from alcohol use disorder. In conclusion, our study provides clinical evidence for altered mGluR5 signaling in the amygdala in alcohol use disorder. This alteration was associated with the temptation to drink. In addition, this study suggests abnormal mGluR5 signaling in a network underlying reward-related behavioral flexibility. These findings strengthen the case for pharmacological agents acting on mGluR5 as promising candidates for the treatment of alcohol user disorder.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Translational Research Center

UniBE Contributor:

Akkus, Funda; Mihov, Yoan Venceslavov and Hasler, Gregor

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2158-3188

Publisher:

Nature Publishing Group

Funders:

[UNSPECIFIED] Universität Bern

Language:

English

Submitter:

Yoan Venceslavov Mihov

Date Deposited:

27 Feb 2018 16:13

Last Modified:

04 Mar 2018 02:18

Publisher DOI:

10.1038/s41398-017-0066-6

PubMed ID:

29317611

BORIS DOI:

10.7892/boris.108424

URI:

https://boris.unibe.ch/id/eprint/108424

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