Valverde O, Noble F, Beslot F, Daugé V, Fournié-Zaluski M C, Roques B P
Département de Pharmacochimie Moléculaire et Structurale, U266 INSERM, UMR 8600 CNRS, UFR des Sciences Pharmaceutiques et Biologiques, 4, Avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Eur J Neurosci. 2001 May;13(9):1816-24. doi: 10.1046/j.0953-816x.2001.01558.x.
Recent studies have suggested that cannabinoids might initiate the consumption of other highly addictive substances, such as opiates. In this work, we show that acute administration of Delta9-tetrahydrocannabinol in mice facilitates the antinociceptive and antidepressant-like responses elicited by the endogenous enkephalins protected from their degradation by RB 101, a complete inhibitor of enkephalin catabolism. This emphasizes the existence of a physiological interaction between endogenous opioid and cannabinoid systems. Accordingly, Delta9-tetrahydrocannabinol increased the release of Met-enkephalin-like material in the nucleus accumbens of awake and freely moving rats measured by microdialysis. In addition, this cannabinoid agonist displaced the in vivo [3H]diprenorphine binding to opioid receptors in total mouse brain. The repetitive pretreatment during 3 weeks of Delta9-tetrahydrocannabinol in mice treated chronically with morphine significantly reduces the naloxone-induced withdrawal syndrome. However, this repetitive administration of Delta9-tetrahydrocannabinol did not modify or even decrease the rewarding responses produced by morphine in the place preference paradigm. Taken together, these behavioural and biochemical results demonstrate the existence of a direct link between endogenous opioid and cannabinoid systems. However, chronic use of high doses of cannabinoids does not seem to potentiate the psychic dependence to opioids.
最近的研究表明，大麻素可能引发对其他高度成瘾物质的消费，比如阿片类药物。在这项研究中，我们发现，给小鼠急性注射Δ9-四氢大麻酚可增强内源性脑啡肽引发的抗伤害感受和抗抑郁样反应，RB 101（一种脑啡肽分解代谢的完全抑制剂）可保护这些内源性脑啡肽不被降解。这凸显了内源性阿片系统和大麻素系统之间存在生理相互作用。相应地，通过微透析法测定，Δ9-四氢大麻酚增加了清醒且自由活动大鼠伏隔核中蛋氨酸脑啡肽样物质的释放。此外，这种大麻素激动剂取代了体内[3H]二丙诺啡与小鼠全脑阿片受体的结合。在长期用吗啡治疗的小鼠中，连续3周对其进行Δ9-四氢大麻酚预处理可显著减轻纳洛酮诱发的戒断综合征。然而，这种对Δ9-四氢大麻酚的重复给药并未改变甚至降低吗啡在位置偏爱范式中产生的奖赏反应。综上所述，这些行为学和生物化学结果证明了内源性阿片系统和大麻素系统之间存在直接联系。然而，长期使用高剂量大麻素似乎并不会增强对阿片类药物的精神依赖。
