Contribution of limbic norepinephrine to cannabinoid-induced aversion

• Author(s): Carvalho, Ana Franky ; Reyes, Arith-Ruth S. ; Sterling, Robert C. ; Unterwald, Ellen ; Bockstaele, Elisabeth J. Van
• Date: 2010
• Persistent ID: http://hdl.handle.net/1822/29625
• Origin: RepositóriUM - Universidade do Minho
• Subject(s): Anxiety; Conditioned place aversion; Nucleus of the solitary tract; Saporin; Mood disorders
• Document Type: Article
• Language: English

Description

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.