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Brief Communications

The Endogenous Cannabinoid 2-Arachidonoylglycerol Is Intravenously Self-Administered by Squirrel Monkeys

Zuzana Justinová, Sevil Yasar, Godfrey H. Redhi and Steven R. Goldberg
Journal of Neuroscience 11 May 2011, 31 (19) 7043-7048; DOI: https://doi.org/10.1523/JNEUROSCI.6058-10.2011
Zuzana Justinová
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Sevil Yasar
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Godfrey H. Redhi
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Steven R. Goldberg
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Abstract

Two endogenous ligands for cannabinoid CB1 receptors, anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol (2-AG), have been identified and characterized. 2-AG is the most prevalent endogenous cannabinoid ligand in the brain, and electrophysiological studies suggest 2-AG, rather than anandamide, is the true natural ligand for cannabinoid receptors and the key endocannabinoid involved in retrograde signaling in the brain. Here, we evaluated intravenously administered 2-AG for reinforcing effects in nonhuman primates. Squirrel monkeys that previously self-administered anandamide or nicotine under a fixed-ratio schedule with a 60 s timeout after each injection had their self-administration behavior extinguished by vehicle substitution and were then given the opportunity to self-administer 2-AG. Intravenous 2-AG was a very effective reinforcer of drug-taking behavior, maintaining higher numbers of self-administered injections per session and higher rates of responding than vehicle across a wide range of doses. To assess involvement of CB1 receptors in the reinforcing effects of 2-AG, we pretreated monkeys with the cannabinoid CB1 receptor inverse agonist/antagonist rimonabant [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide]. Rimonabant produced persistent blockade of 2-AG self-administration without affecting responding maintained by food under similar conditions. Thus, 2-AG was actively self-administered by monkeys with or without a history of cannabinoid self-administration, and the reinforcing effects of 2-AG were mediated by CB1 receptors. Self-administration of 2-AG by squirrel monkeys provides a valuable procedure for studying abuse liability of medications that interfere with 2-AG signaling within the brain and for investigating mechanisms involved in the reinforcing effects of endocannabinoids.

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The Journal of Neuroscience: 31 (19)
Journal of Neuroscience
Vol. 31, Issue 19
11 May 2011
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The Endogenous Cannabinoid 2-Arachidonoylglycerol Is Intravenously Self-Administered by Squirrel Monkeys
Zuzana Justinová, Sevil Yasar, Godfrey H. Redhi, Steven R. Goldberg
Journal of Neuroscience 11 May 2011, 31 (19) 7043-7048; DOI: 10.1523/JNEUROSCI.6058-10.2011

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The Endogenous Cannabinoid 2-Arachidonoylglycerol Is Intravenously Self-Administered by Squirrel Monkeys
Zuzana Justinová, Sevil Yasar, Godfrey H. Redhi, Steven R. Goldberg
Journal of Neuroscience 11 May 2011, 31 (19) 7043-7048; DOI: 10.1523/JNEUROSCI.6058-10.2011
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