Back to Search Start Over

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

Authors :
Anderson SA
Michaelides M
Zarnegar P
Ren Y
Fagergren P
Thanos PK
Wang GJ
Bannon M
Neumaier JF
Keller E
Volkow ND
Hurd YL
Source :
The Journal of clinical investigation [J Clin Invest] 2013 Dec; Vol. 123 (12), pp. 5334-41. Date of Electronic Publication: 2013 Nov 15.
Publication Year :
2013

Abstract

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.

Details

Language :
English
ISSN :
1558-8238
Volume :
123
Issue :
12
Database :
MEDLINE
Journal :
The Journal of clinical investigation
Publication Type :
Academic Journal
Accession number :
24231353
Full Text :
https://doi.org/10.1172/JCI70395