Meyer Paul J, Fossum Erin N, Ingram Susan L, Morgan Michael M
Washington State University Vancouver, 14204 NE Salmon Creek Ave, Vancouver, WA 98660, USA.
Neuropharmacology. 2007 Jun;52(8):1580-5. doi: 10.1016/j.neuropharm.2007.03.002. Epub 2007 Mar 12.
Repeated administration of the relatively low-efficacy micro-opioid receptor agonist morphine induces tolerance to its antinociceptive effects. High-efficacy agonists such as D-Ala2NMePhe4,Gly-ol5 (DAMGO) have been shown to be less effective at producing tolerance, suggesting that different neural mechanisms underlie tolerance to these agonists. However, the correlation between agonist efficacy and tolerance development has not been examined within the ventrolateral periaqueductal gray (vPAG), a brain area known to be crucial for the development of morphine tolerance. The current studies examined whether tolerance to DAMGO occurs within the vPAG, and whether repeated treatment with DAMGO into the vPAG alters the development of morphine tolerance. The results showed that repeated vPAG microinjections of DAMGO induced robust tolerance and cross-tolerance to morphine. Further, co-administration of a low dose of DAMGO with morphine potentiated morphine tolerance. These findings indicate that similar mechanisms underlie tolerance to morphine and DAMGO within the vPAG.
相对低效的微阿片受体激动剂吗啡的反复给药会诱导对其镇痛作用产生耐受性。已表明高效激动剂，如D-Ala2NMePhe4，Gly-ol5（DAMGO）在产生耐受性方面效果较差，这表明对这些激动剂产生耐受性的神经机制不同。然而，激动剂效力与耐受性发展之间的相关性尚未在腹外侧导水管周围灰质（vPAG）中进行研究，已知该脑区对吗啡耐受性的发展至关重要。当前的研究考察了在vPAG内是否会出现对DAMGO的耐受性，以及向vPAG反复注射DAMGO是否会改变吗啡耐受性的发展。结果表明，向vPAG反复微量注射DAMGO会诱导对吗啡产生强大的耐受性和交叉耐受性。此外，低剂量的DAMGO与吗啡共同给药会增强吗啡耐受性。这些发现表明，vPAG内对吗啡和DAMGO产生耐受性的机制相似。
