liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A Novel Brain Penetrant NPS Receptor Antagonist, NCGC00185684, Blocks Alcohol-Induced ERK-Phosphorylation in the Central Amygdala and Decreases Operant Alcohol Self-Administration in Rats
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
National Center for Advancing Translational Sciences, Bethesda, Maryland, USA.
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
Show others and affiliations
2013 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 33, no 24, 10132-10142 p.Article in journal (Refereed) Published
Abstract [en]

The Neuropeptide S receptor, a Gs/Gq-coupled GPCR expressed in brain regions involved in mediating drug reward, has recently emerged as a candidate therapeutic target in addictive disorders. Here, we describe the in vitro and in vivo pharmacology of a novel, selective and brain penetrant NPSR antagonist with nanomolar affinity for the NPSR, NCGC00185684. In vitro, NCGC00185684 shows biased antagonist properties, and preferentially blocks ERK-phosphorylation over intracellular cAMP or calcium responses to NPS. In vivo, systemic NCGC00185684 blocks alcohol-induced ERK-phosphorylation in the rat central amygdala, a region involved in regulation of alcohol intake. NCGC00185684 also decreases operant alcohol self-administration, and lowers motivation for alcohol reward as measured using progressive ratio responding. These effects are behaviorally specific, in that they are observed at doses that do not influence locomotor activity or reinstatement responding following extinction. Together, these data provide an initial validation of the NPSR as a therapeutic target in alcoholism.

Place, publisher, year, edition, pages
Society for Neuroscience , 2013. Vol. 33, no 24, 10132-10142 p.
Keyword [en]
addiction, neuropeptide S, phosphorylation
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-94652DOI: 10.1523/JNEUROSCI.4742-12.2013ISI: 000320235300028PubMedID: 23761908OAI: oai:DiVA.org:liu-94652DiVA: diva2:634181
Available from: 2013-06-28 Created: 2013-06-28 Last updated: 2017-12-06Bibliographically approved

Open Access in DiVA

fulltext(2698 kB)431 downloads
File information
File name FULLTEXT01.pdfFile size 2698 kBChecksum SHA-512
6f1f9441792fee02ba1000b71d25fc9b3fdb1cdc423e67efe87562a276a8c8f090ffea1125f03db38cf1ffaa4e54688b71f3eafedea27079461c0a398cf7992f
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Thorsell, AnnikaHeilig, Markus

Search in DiVA

By author/editor
Thorsell, AnnikaHeilig, Markus
By organisation
Division of Cell BiologyFaculty of Health Sciences
In the same journal
Journal of Neuroscience
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 431 downloads
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

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 157 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf