Hodges Erik L, Marshall Jessica P, Ashpole Nicole M
Department of BioMolecular Sciences, Pharmacology Division, University of Mississippi School of Pharmacy, University, Oxford, MS USA.
Research Institute of Pharmaceutical Sciences, University of Mississippi School of Pharmacy, University, Oxford, MS USA.
NPJ Aging Mech Dis. 2020 Jul 6;6:7. doi: 10.1038/s41514-020-0045-7. eCollection 2020.
Use of cannabis and cannabinoid-containing substances is increasing among geriatric patients, despite relatively sparse preclinical evidence in aged models. To better understand the effects of exogenous cannabinoids on aging male and female rodents, we compared the age- and dose-dependent physiological and behavioral effects of the synthetic cannabinoid CP55940 in young-adult and aged C57BL/6 mice. Locomotion, body temperature, thermal nociception, and fecal output were measured following CP55940 administration. Our findings indicate that CP55940 is more potent and efficacious in older mice, evidenced by exaggerated antinociception and locomotor inhibition when compared to younger adult mice. In addition, we report that low doses of CP55940 paradoxically stimulate locomotion in young-adult (4 m) mice; however, this hormesis-like response is not as evident in aged animals (21-24 m). These bidirectional effects appear to be mediated via the endocannabinoid CB1 and CB2 receptors.
尽管在老年模型中的临床前证据相对较少，但大麻和含大麻素物质在老年患者中的使用正在增加。为了更好地了解外源性大麻素对衰老的雄性和雌性啮齿动物的影响，我们比较了合成大麻素CP55940在年轻成年和老年C57BL/6小鼠中的年龄和剂量依赖性生理和行为影响。在给予CP55940后，测量运动、体温、热痛觉和粪便输出。我们的研究结果表明，CP55940在老年小鼠中更有效力和效果，与年轻成年小鼠相比，其抗伤害感受和运动抑制作用更为明显。此外，我们报告低剂量的CP55940反常地刺激年轻成年（4个月）小鼠的运动；然而，这种类似兴奋效应的反应在老年动物（21-24个月）中并不明显。这些双向效应似乎是通过内源性大麻素CB1和CB2受体介导的。
