Department of Psychology and Collaborative, University of Guelph, Guelph, Ontario, N1H 2GW, Canada.
Institute of Biomolecular Chemistry, Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy.
Psychopharmacology (Berl). 2019 Sep;236(9):2623-2633. doi: 10.1007/s00213-019-05237-9. Epub 2019 Apr 16.
Oleoyl glycine (OlGly), a recently discovered fatty acid amide that is structurally similar to N- acylethanolamines, which include the endocannabinoid, anandamide (AEA), as well as endogenous peroxisome proliferator-activated receptor alpha (PPARα) agonists oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), has been shown to interfere with nicotine reward and dependence in mice.
Behavioral and molecular techniques were used to investigate the ability of OlGly to interfere with the affective properties of morphine and morphine withdrawal (MWD) in male Sprague-Dawley rats.
Synthetic OlGly (1-30 mg/kg, intraperitoneal [ip]) produced neither a place preference nor aversion on its own; however, at doses of 1 and 5 mg/kg, ip, it blocked the aversive effects of MWD in a place aversion paradigm. This effect was reversed by the cannabinoid 1 (CB1) receptor antagonist, AM251 (1 mg/kg, ip), but not the PPARα antagonist, MK886 (1 mg/kg, ip). OlGly (5 or 30 mg/kg, ip) did not interfere with a morphine-induced place preference or reinstatement of a previously extinguished morphine-induced place preference. Ex vivo analysis of tissue (nucleus accumbens, amygdala, prefrontal cortex, and interoceptive insular cortex) collected from rats experiencing naloxone-precipitated MWD revealed that OlGly was selectively elevated in the nucleus accumbens. MWD did not modify levels of the endocannabinoids 2-AG and AEA, nor those of the PPARα ligands, OEA and PEA, in any region evaluated.
Here, we show that OlGly interferes with the aversive properties of acute naloxone-precipitated morphine withdrawal in rats. These results suggest that OlGly may reduce the impact of MWD and may possess efficacy in treating opiate withdrawal.
油酰甘氨酸（OlGly）是一种最近发现的脂肪酸酰胺，其结构与内源性大麻素相似，包括大麻素受体激动剂，如花生四烯酸乙醇酰胺（AEA），以及内源性过氧化物酶体增殖物激活受体 α（PPARα）激动剂，油酰乙醇酰胺（OEA）和棕榈酰乙醇酰胺（PEA），已被证明可干扰小鼠的尼古丁奖赏和依赖性。
采用行为学和分子技术研究 OlGly 干扰雄性 Sprague-Dawley 大鼠吗啡的情感属性以及吗啡戒断（MWD）的能力。
合成的 OlGly（1-30mg/kg，腹腔内[ip]）本身既不会引起位置偏好也不会引起厌恶；然而，在 1 和 5mg/kg，ip 剂量下，它会在位置厌恶范式中阻断 MWD 的厌恶作用。这种作用可被大麻素 1（CB1）受体拮抗剂 AM251（1mg/kg，ip）逆转，但不能被 PPARα 拮抗剂 MK886（1mg/kg，ip）逆转。OlGly（5 或 30mg/kg，ip）不会干扰吗啡诱导的位置偏好或先前消除的吗啡诱导的位置偏好的恢复。从经历纳洛酮诱发的 MWD 的大鼠收集的组织（伏隔核、杏仁核、前额叶皮层和内脏岛叶皮层）的体外分析显示，OlGly 选择性地在伏隔核中升高。MWD 并未改变任何评估区域中的内源性大麻素 2-AG 和 AEA 的水平，也未改变 PPARα 配体 OEA 和 PEA 的水平。
在这里，我们表明 OlGly 可干扰大鼠急性纳洛酮诱发的吗啡戒断的厌恶属性。这些结果表明 OlGly 可能减轻 MWD 的影响，并可能在治疗阿片类药物戒断方面具有疗效。
