Modulation of Morphine Analgesia, Antinociceptive Tolerance, and Mu-Opioid Receptor Binding by the Cannabinoid CB2 Receptor Agonist O-1966

• DOI: 10.3389/fphar.2022.803331
• Publication Date: 2022-04-21T04:48:35Z
• Authors: Zachary W. Reiche...; Kelly DiMattio; Suren Rajakaruna; David Ambrose; William D. Cornwell; Ronald J. Tallarida; Thomas Rogers; Lee-Yuan Liu-Chen; Ronald F. Tuma; Sara Jane Ward
• Keywords: DAMGO; μ-opioid receptor

Acutely, non-selective cannabinoid (CB) agonists have been shown to increase morphine antinociceptive effects, and we others also demonstrated that CB attenuate tolerance. Activation of CB2 receptors reverses allodynia hyperalgesia in models chronic pain, co-administration with receptor selective has be synergistic. activation reduce morphine-induced rodents, an effect attributed modulation inflammation. In the present set experiments, tested both acute interactions between agonist O-1966 treatments on antinociception tolerance C57Bl6 mice. Co-administration was under three dosing regimens: simultaneous administration, pre-treated O-1966, morphine. The effects mu-opioid binding were determined using [3H]DAMGO [35S]GTPγS assays, these further examined by FRET analysis linked flow cytometry. Results yielded surprising evidence dependent upon order administration. When administered prior or morphine, attenuated exacerbated. following not affected attenuated. results suggest interrupts functional activity at receptor, leading decreased potency produce thermal potentiation However, after blocked led attenuation tolerance, perhaps due well-documented anti-inflammatory agonism.