uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Reverse Pharmacogenetic Modulation of the Nucleus Accumbens Reduces Ethanol Consumption in a Limited Access Paradigm
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Show others and affiliations
2014 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1470-634X, Vol. 39, no 2, 283-290 p.Article in journal (Refereed) Published
Abstract [en]

Bilateral stereotactic lesioning of the nucleus accumbens (NAc) core reduces relapse rates in alcohol-dependent patients but may cause irreversible cognitive deficits. Deep brain stimulation has similar effects but requires costly implanted hardware and regular surgical maintenance. Therefore, there is considerable interest in refining these approaches to develop reversible, minimally invasive treatments for alcohol dependence. Toward this end, we evaluated the feasibility of a reverse pharmacogenetic approach in a preclinical mouse model. We first assessed the predictive validity of a limited access ethanol consumption paradigm by confirming that electrolytic lesions of the NAc core decreased ethanol consumption, recapitulating the effects of similar lesions in humans. We then used this paradigm to test the effect of modulating activity in the NAc using the Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) hM3Dq and hM4Di. We found that increasing activity with hM3Dq had no effect, but suppressing activity with hM4Di reduced alcohol consumption to a similar extent as lesioning without affecting consumption of water or sucrose. These results may represent early steps toward a novel neurosurgical treatment modality for alcohol dependence that is reversible and externally titratable, yet highly targetable and less invasive than current approaches such as lesioning or deep brain stimulation.

Place, publisher, year, edition, pages
2014. Vol. 39, no 2, 283-290 p.
Keyword [en]
alcohol dependence, reverse pharmacogenetics, nucleus accumbens, drinking in the dark, DREADDs
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-216060DOI: 10.1038/npp.2013.184ISI: 000328585400005OAI: oai:DiVA.org:uu-216060DiVA: diva2:689174
Available from: 2014-01-20 Created: 2014-01-17 Last updated: 2014-01-20Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text
By organisation
Department of Neuroscience
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 158 hits
ReferencesLink to record
Permanent link

Direct link