Deletion of the type 2 metabotropic glutamate receptor increases heroin abuse vulnerability in transgenic rats.

Study Authors Jun-tao Gao (inset) and Chloe Jordan

Featured Paper of the Month – February 2019.

Despite extensive research in the past decades, little is known about the etiology of opioid addiction. In this study, Xi and colleagues found that genetic deletion of mGluR2, a glutamate receptor subtype, in rats caused an increase in brain dopamine responses to heroin and in opioid reward, facilitating the development of opioid use and abuse. This finding suggests that low-mGluR2 expression in the brain may be a risk factor for the development of opioid abuse and addiction.

Publication Information

Gao, Jun-Tao; Jordan, Chloe J; Bi, Guo-Hua; He, Yi; Yang, Hong-Ju; Gardner, Eliot L; Xi, Zheng-Xiong

Deletion of the type 2 metabotropic glutamate receptor increases heroin abuse vulnerability in transgenic rats. Journal Article

In: Neuropsychopharmacology, vol. 43, no. 13, pp. 2615–2626, 2018, ISSN: 1740-634X (Electronic); 0893-133X (Linking).

Abstract | Links

@article{Gao:2018aa,

title = {Deletion of the type 2 metabotropic glutamate receptor increases heroin abuse vulnerability in transgenic rats.},

author = {Jun-Tao Gao and Chloe J Jordan and Guo-Hua Bi and Yi He and Hong-Ju Yang and Eliot L Gardner and Zheng-Xiong Xi},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30283001},

doi = {10.1038/s41386-018-0231-5},

issn = {1740-634X (Electronic); 0893-133X (Linking)},

year  = {2018},

date = {2018-12-01},

urldate = {2018-12-01},

journal = {Neuropsychopharmacology},

volume = {43},

number = {13},

pages = {2615--2626},

address = {Addiction Biology Unit, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, 21224, USA.},

abstract = {Opioid abuse is a rapidly growing public health crisis in the USA. Despite extensive research in the past decades, little is known about the etiology of opioid addiction or the neurobiological risk factors that increase vulnerability to opioid use and abuse. Recent studies suggest that the type 2 metabotropic glutamate receptor (mGluR2) is critically involved in substance abuse and addiction. In the present study, we evaluated whether low-mGluR2 expression may represent a risk factor for the development of opioid abuse and addiction using transgenic mGluR2-knockout (mGluR2-KO) rats. Compared to wild-type controls, mGluR2-KO rats exhibited higher nucleus accumbens (NAc) dopamine (DA) and locomotor responses to heroin, higher heroin self-administration and heroin intake, more potent morphine-induced analgesia and more severe naloxone-precipitated withdrawal symptoms. In contrast, mGluR2-KO rats displayed lower motivation for heroin self-administration under high price progressive-ratio (PR) reinforcement conditions. Taken together, these findings suggest that mGluR2 may play an inhibitory role in opioid action, such that deletion of this receptor results in an increase in brain DA responses to heroin and in acute opioid reward and analgesia. Low-mGluR2 expression in the brain may therefore be a risk factor for the initial development of opioid abuse and addiction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}