RGD Reference Report - Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression. - Rat Genome Database

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Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression.

Authors: Anderson, Sarah Ann R  Michaelides, Michael  Zarnegar, Parisa  Ren, Yanhua  Fagergren, Pernilla  Thanos, Panayotis K  Wang, Gene-Jack  Bannon, Michael  Neumaier, John F  Keller, Eva  Volkow, Nora D  Hurd, Yasmin L 
Citation: Anderson SA, etal., J Clin Invest. 2013 Dec;123(12):5334-41. doi: 10.1172/JCI70395. Epub 2013 Nov 15.
RGD ID: 401850554
Pubmed: PMID:24231353   (View Abstract at PubMed)
PMCID: PMC3859405   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI70395   (Journal Full-text)

Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chronically self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted metabolic mapping, where DREADD indicates designer receptors exclusively activated by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect-related physiological and behavioral changes. Altogether, our translational study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDYNHumanheroin dependence  IEP mRNA:decreased expression:periamygdaloid cortexRGD 
PdynRatheroin dependence  ISOPDYN (Homo sapiens)mRNA:decreased expression:periamygdaloid cortexRGD 
PdynMouseheroin dependence  ISOPDYN (Homo sapiens)mRNA:decreased expression:periamygdaloid cortexRGD 
PDYNHumanmajor depressive disorder  IEP mRNA:decreased expression:periamygdaloid cortexRGD 
PdynRatmajor depressive disorder  ISOPDYN (Homo sapiens)mRNA:decreased expression:periamygdaloid cortexRGD 
PdynMousemajor depressive disorder  ISOPDYN (Homo sapiens)mRNA:decreased expression:periamygdaloid cortexRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdyn  (prodynorphin)

Genes (Mus musculus)
Pdyn  (prodynorphin)

Genes (Homo sapiens)
PDYN  (prodynorphin)


Additional Information