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The cannabinoid CB(1) receptor antagonist SR141716A increases norepinephrine outflow in the rat anterior hypothalamus
E T Tzavara1, K W Perry, D E Rodriguez
1Eli Lilly & Company, Lilly Corporate Center, Neuroscience Discovery Research, Indianapolis, IN 46285-0510, USA.
Abstract:
The effects of the selective cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide-hydrochloride (SR141716A) on extracellular concentrations of norepinephrine and 5-hydroxytryptamine (5-HT) were assessed by in vivo microdialysis in the anterior hypothalamus of freely moving rats. SR14716A (0.3, 1, 3 mg/kg, i.p.) dose-dependently increased norepinephrine efflux to about 300% of baseline, without affecting 5-HT levels. This increase in norepinephrine outflow could play an important role in the pharmacological and potentially therapeutic actions of SR141716A.
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