Justinova Zuzana, Solinas Marcello, Tanda Gianluigi, Redhi Godfrey H, Goldberg Steven R
Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA.
J Neurosci. 2005 Jun 8;25(23):5645-50. doi: 10.1523/JNEUROSCI.0951-05.2005.
Anandamide, an endogenous ligand for brain cannabinoid CB(1) receptors, produces many behavioral effects similar to those of Delta(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 CB(1) receptor antagonist rimonabant (SR141716). These findings strongly suggest that release of endogenous cannabinoids is involved in brain reward processes and that activation of cannabinoid CB(1) receptors by anandamide could be part of the signaling of natural rewarding events.
花生四烯乙醇胺是大脑大麻素CB(1)受体的内源性配体，其产生的许多行为效应与大麻中的主要精神活性成分Δ9-四氢大麻酚（THC）相似。THC的强化作用已在实验动物中得到证实，但仅有间接证据表明内源性大麻素如花生四烯乙醇胺参与大脑奖赏过程。我们现在表明，当松鼠猴静脉内自我给药时，花生四烯乙醇胺可作为药物摄取行为的有效强化剂。我们还表明，甲酰化花生四烯乙醇胺，一种合成的长效花生四烯乙醇胺类似物，同样可作为药物摄取行为的强化剂。最后，我们表明，花生四烯乙醇胺和甲酰化花生四烯乙醇胺的强化作用均可被大麻素CB(1)受体拮抗剂利莫那班（SR141716）预处理所阻断。这些发现强烈表明内源性大麻素的释放参与大脑奖赏过程，并且花生四烯乙醇胺对大麻素CB(1)受体的激活可能是自然奖赏事件信号传导的一部分。
