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Contribution of limbic norepinephrine to cannabinoid-induced aversion
Journal article   Open access   Peer reviewed

Contribution of limbic norepinephrine to cannabinoid-induced aversion

Ana Franky Carvalho, Arith-Ruth S. Reyes, Robert C. Sterling, Ellen Unterwald and Elisabeth J. Van Bockstaele
Psychopharmacology, v 211(4), pp 479-491
01 Sep 2010
PMID: 20602088
url
https://europepmc.org/articles/pmc3272334View
Accepted (AM)Open Access (License Unspecified) Open
url
https://doi.org/10.1007/s00213-010-1923-7View
Published, Version of Record (VoR) Open

Abstract

Biomedical and Life Sciences Biomedicine Neurosciences Original Investigation Pharmacology/Toxicology Psychiatry
Rationale The cannabinoid system has risen to the forefront in the development of novel treatments for a number of pathophysiological processes. However, significant side effects have been observed in clinical trials raising concerns regarding the potential clinical utility of cannabinoid-based agents. Understanding the neural circuits and neurochemical substrates impacted by cannabinoids will provide a better means of gaging their actions within the central nervous system that may contribute to the expression of unwanted side effects. Objectives In the present study, we investigated whether norepinephrine (NE) in the limbic forebrain is a critical determinant of cannabinoid receptor agonist-induced aversion and anxiety in rats. Methods An immunotoxin lesion approach was combined with behavioral analysis using a place conditioning paradigm and the elevated zero maze. Results Our results show that the non-selective CB1/CB2 receptor agonist, WIN 55,212-2, produced a significant place aversion in rats. Further, NE in the nucleus accumbens was critical for WIN 55,212-2-induced aversion but did not affect anxiety-like behaviors. Depletion of NE from the bed nucleus of the stria terminalis was ineffective in altering WIN 55,212-2-induced aversion and anxiety. Conclusions These results indicate that limbic, specifically accumbal, NE is required for cannabinoid-induced aversion but is not essential to cannabinoid-induced anxiety.

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25 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Neurosciences
Pharmacology & Pharmacy
Psychiatry
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