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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

Thorsell, Annika, 1970- (author)
Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet
Tapocik, Jenica D (author)
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
Liu, Ke (author)
National Center for Advancing Translational Sciences, Bethesda, Maryland, USA
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Zook, Michelle (author)
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
Bell, Lauren (author)
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
Flanigan, Meghan (author)
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
Patnaik, Samarjit (author)
National Center for Advancing Translational Sciences, Bethesda, Maryland, USA
Marugan, Juan (author)
National Center for Advancing Translational Sciences, Bethesda, Maryland, USA
Damadzic, Ruslan (author)
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
Dehdashti, Seameen J (author)
National Center for Advancing Translational Sciences, Bethesda, Maryland, USA
Schwandt, Melanie L (author)
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
Southall, Noel (author)
National Center for Advancing Translational Sciences, Bethesda, Maryland, USA
Austin, Christopher P (author)
National Center for Advancing Translational Sciences, Bethesda, Maryland, USA
Eskay, Robert (author)
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
Ciccocioppo, Roberto (author)
University of Camerino, Italy
Zheng, Wei (author)
National Center for Advancing Translational Sciences, Bethesda, Maryland, USA
Heilig, Markus (author)
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA
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 (creator_code:org_t)
Society for Neuroscience, 2013
2013
English.
In: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 33:24, s. 10132-10142
Related links:
https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

addiction
neuropeptide S
phosphorylation

Publication and Content Type

ref (subject category)
art (subject category)

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