Rock Erin M, Limebeer Cheryl L, Sullivan Megan T, DeVuono Marieka V, Lichtman Aron H, Di Marzo Vincenzo, Mechoulam Raphael, Parker Linda A
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States.
Front Synaptic Neurosci. 2021 Mar 9;13:620145. doi: 10.3389/fnsyn.2021.620145. eCollection 2021.
The endogenous amide -Oleoylglycine (OlGly) and its analog -Oleoylalanine (OlAla), have been shown to interfere with the affective and somatic responses to acute naloxone-precipitated MWD in male rats. Here we evaluated the potential of a single dose (5 mg/kg, ip) which alleviates withdrawal of these endogenous fatty acid amides to modify tolerance to anti-nociception, hyperthermia, and suppression of locomotion produced by morphine in male Sprague-Dawley rats. Although rats did develop tolerance to the hypolocomotor and analgesic effects of morphine, they did not develop tolerance to the hyperthermic effects of this substance. Administration of neither OlGly nor OlAla interfered with the establishment of morphine tolerance, nor did they modify behavioral responses elicited by morphine on any trial. These results suggest that the effects of OlGly and OlAla on opiate dependence may be limited to naloxone-precipitated withdrawal effects.
内源性酰胺——油酰甘氨酸（OlGly）及其类似物——油酰丙氨酸（OlAla）已被证明会干扰雄性大鼠对急性纳洛酮诱发的吗啡戒断反应的情感和躯体反应。在此，我们评估了单剂量（5毫克/千克，腹腔注射）可减轻这些内源性脂肪酸酰胺戒断反应的物质，对雄性斯普拉格-道利大鼠吗啡诱导的抗伤害感受、体温过高及运动抑制耐受性的影响。尽管大鼠确实对吗啡的运动减少和镇痛作用产生了耐受性，但它们并未对该物质的体温过高作用产生耐受性。给予OlGly和OlAla均未干扰吗啡耐受性的建立，在任何试验中它们也未改变吗啡引发的行为反应。这些结果表明，OlGly和OlAla对阿片类药物依赖的影响可能仅限于纳洛酮诱发的戒断效应。
