RGD Reference Report - Deletion of the type 2 metabotropic glutamate receptor increases heroin abuse vulnerability in transgenic rats. - Rat Genome Database

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

Authors: Gao, Jun-Tao  Jordan, Chloe J  Bi, Guo-Hua  He, Yi  Yang, Hong-Ju  Gardner, Eliot L  Xi, Zheng-Xiong 
Citation: Gao JT, etal., Neuropsychopharmacology. 2018 Dec;43(13):2615-2626. doi: 10.1038/s41386-018-0231-5. Epub 2018 Oct 3.
RGD ID: 38501063
Pubmed: PMID:30283001   (View Abstract at PubMed)
PMCID: PMC6224385   (View Article at PubMed Central)
DOI: DOI:10.1038/s41386-018-0231-5   (Journal Full-text)

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.



Disease Annotations    
heroin dependence  (IMP,ISO)

Gene Ontology Annotations    

Biological Process

Phenotype Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Grm2  (glutamate metabotropic receptor 2)
Grm2em1  (glutamate metabotropic receptor 2; endonuclease induced mutant 1)

Genes (Mus musculus)
Grm2  (glutamate receptor, metabotropic 2)

Genes (Homo sapiens)
GRM2  (glutamate metabotropic receptor 2)

Strains
WI-Grm2em1  (NA)


Additional Information