Abstinence-dependent dissociable central amygdala microcircuits control drug craving

Hot Off the Press – March 27 , 2020.

The current study offers a mechanistic explanation for the protective effect of social interaction on incubation of craving in rodents, showing that it is mediated by the activation of neurons expressing the enzyme PKCδ the brain’s amygdala. The study also shows that activation of a peptide called somatostatin in the amygdala is critical for incubation of drug craving after forced abstinence in the homecage. The study also introduced novel viral tools that will allow other researchers to mechanistically study the role of PKCδ and somatostatin in learned and motivated behaviors related to drug use disorders, as well as other psychiatric disorders.

Publication Information

Venniro, Marco; Russell, Trinity I; Ramsey, Leslie A; Richie, Christopher T; Lesscher, Heidi M B; Giovanetti, Simone M; Messing, Robert O; Shaham, Yavin

Abstinence-dependent dissociable central amygdala microcircuits control drug craving. Journal Article

In: Proc Natl Acad Sci U S A, 2019, ISSN: 1091-6490 (Electronic); 0027-8424 (Linking).

Abstract | Links

@article{Venniro:2020fk,

title = {Abstinence-dependent dissociable central amygdala microcircuits control drug craving.},

author = {Marco Venniro and Trinity I Russell and Leslie A Ramsey and Christopher T Richie and Heidi M B Lesscher and Simone M Giovanetti and Robert O Messing and Yavin Shaham},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32205443},

doi = {10.1073/pnas.2001615117},

issn = {1091-6490 (Electronic); 0027-8424 (Linking)},

year  = {2019},

date = {2019-03-23},

urldate = {2019-03-23},

journal = {Proc Natl Acad Sci U S A},

address = {Behavioral Neuroscience Branch Intramural Research Program, National Institute on Drug Abuse (NIDA), NIH, Baltimore, MD 21224; venniro.marco@nih.gov yshaham@intra.nida.nih.gov.},

abstract = {We recently reported that social choice-induced voluntary abstinence prevents incubation of methamphetamine craving in rats. This inhibitory effect was associated with activation of protein kinase-Cdelta (PKCdelta)-expressing neurons in central amygdala lateral division (CeL). In contrast, incubation of craving after forced abstinence was associated with activation of CeL-expressing somatostatin (SOM) neurons. Here we determined the causal role of CeL PKCdelta and SOM in incubation using short-hairpin RNAs against PKCdelta or SOM that we developed and validated. We injected two groups with shPKCdelta or shCtrlPKCdelta into CeL and trained them to lever press for social interaction (6 d) and then for methamphetamine infusions (12 d). We injected two other groups with shSOM or shCtrlSOM into CeL and trained them to lever press for methamphetamine infusions (12 d). We then assessed relapse to methamphetamine seeking after 1 and 15 abstinence days. Between tests, the rats underwent either social choice-induced abstinence (shPKCdelta groups) or homecage forced abstinence (shSOM groups). After test day 15, we assessed PKCdelta and SOM, Fos, and double-labeled expression in CeL and central amygdala medial division (CeM). shPKCdelta CeL injections decreased Fos in CeL PKCdelta-expressing neurons, increased Fos in CeM output neurons, and reversed the inhibitory effect of social choice-induced abstinence on incubated drug seeking on day 15. In contrast, shSOM CeL injections decreased Fos in CeL SOM-expressing neurons, decreased Fos in CeM output neurons, and decreased incubated drug seeking after 15 forced abstinence days. Our results identify dissociable central amygdala mechanisms of abstinence-dependent expression or inhibition of incubation of craving.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}