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The Journal of Neuroscience, June 8, 2005, 25(23):5645-5650; doi:10.1523/JNEUROSCI.0951-05.2005

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BRIEF COMMUNICATION
The Endogenous Cannabinoid Anandamide and Its Synthetic Analog R(+)-Methanandamide Are Intravenously Self-Administered by Squirrel Monkeys

Zuzana Justinova,¹ Marcello Solinas,^1,3 Gianluigi Tanda,² Godfrey H. Redhi,¹ and Steven R. Goldberg¹

¹Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch and ²Psychobiology Section, Medications Discovery Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland, 21224, and ³Laboratoire de Biologie et Physiologie Cellulaire, Université de Poitiers, 86022, Poitiers, France

Anandamide, an endogenous ligand for brain cannabinoid CB₁ receptors, produces many behavioral effects similar to those of ⁹-tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana. Reinforcing effects of THC have been demonstrated in experimental animals, but there is only indirect evidence that endogenous cannabinoids such as anandamide participate in brain reward processes. We now show that anandamide serves as an effective reinforcer of drug-taking behavior when self-administered intravenously by squirrel monkeys. We also show that methanandamide, a synthetic long-lasting anandamide analog, similarly serves as a reinforcer of drug-taking behavior. Finally, we show that the reinforcing effects of both anandamide and methanandamide are blocked by pretreatment with the cannabinoid CB₁ receptor antagonist rimonabant (SR141716). These findings strongly suggest that release of endogenous cannabinoids is involved in brain reward processes and that activation of cannabinoid CB₁ receptors by anandamide could be part of the signaling of natural rewarding events.

Key words: anandamide; cannabinoids; methanandamide; reinforcing effects; self-administration; squirrel monkey

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Received March 10, 2005; revised May 6, 2005; accepted May 7, 2005.

This article has been cited by other articles:

				M. Solinas, G. Tanda, Z. Justinova, C. E. Wertheim, S. Yasar, D. Piomelli, S. K. Vadivel, A. Makriyannis, and S. R. Goldberg The Endogenous Cannabinoid Anandamide Produces {delta}-9-Tetrahydrocannabinol-Like Discriminative and Neurochemical Effects That Are Enhanced by Inhibition of Fatty Acid Amide Hydrolase but Not by Inhibition of Anandamide Transport J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 370 - 380. [Abstract] [Full Text] [PDF]

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