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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GRM2Humanheroin dependence  ISOGrm2 (Rattus norvegicus) RGD 
Grm2Ratheroin dependence  IMP  RGD 
Grm2Mouseheroin dependence  ISOGrm2 (Rattus norvegicus) RGD 
Grm2em1Ratheroin dependence  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratheroin dependence  IMP KO compared to wild-type ratsRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Grm2Ratregulation of dopamine secretion  IMP  RGD 
Grm2Ratregulation of glutamate secretion  IMP  RGD 
Grm2Ratregulation of response to drug  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Grm2Ratabnormal behavioral response to addictive substance  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratabnormal behavioral response to addictive substance  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratabnormal behavioral response to addictive substance  IMP KO compared to wild-type ratsRGD 
Grm2Ratabnormal behavioral response to morphine  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratabnormal behavioral response to morphine  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratabnormal behavioral response to morphine  IMP KO compared to wild-type ratsRGD 
Grm2Ratabnormal behavioral withdrawal response  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratabnormal behavioral withdrawal response  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratabnormal behavioral withdrawal response  IMP KO compared to wild-type ratsRGD 
Grm2Ratabnormal cue-induced reinstatement of an extinguished operant behavior for a cocaine reinforcer  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratabnormal cue-induced reinstatement of an extinguished operant behavior for a cocaine reinforcer  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratabnormal cue-induced reinstatement of an extinguished operant behavior for a cocaine reinforcer  IMP KO compared to wild-type ratsRGD 
Grm2Ratabnormal neurotransmitter secretion  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratabnormal neurotransmitter secretion  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratabnormal neurotransmitter secretion  IMP KO compared to wild-type ratsRGD 
Grm2Ratabnormal nocifensive behavior  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratabnormal nocifensive behavior  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratabnormal nocifensive behavior  IMP KO compared to wild-type ratsRGD 
Grm2Ratenhanced behavioral response to morphine  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratenhanced behavioral response to morphine  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratenhanced behavioral response to morphine  IMP KO compared to wild-type ratsRGD 
Grm2Rathigh preference for an addictive substance  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Rathigh preference for an addictive substance  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Rathigh preference for an addictive substance  IMP KO compared to wild-type ratsRGD 
Grm2Ratincreased chemically-elicited antinociception  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratincreased chemically-elicited antinociception  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratincreased chemically-elicited antinociception  IMP KO compared to wild-type ratsRGD 
Grm2Ratincreased nervous system dopamine level  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratincreased nervous system dopamine level  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratincreased nervous system dopamine level  IMP KO compared to wild-type ratsRGD 
Grm2Ratincreased thermal nociceptive threshold  IMP knock-out compared to wild-type ratsRGD 
Grm2em1Ratincreased thermal nociceptive threshold  IMP KO compared to wild-type ratsRGD 
WI-Grm2em1Ratincreased thermal nociceptive threshold  IMP KO compared to wild-type ratsRGD 
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