Effects of (2R,6R)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice

被引:0
作者
Hillhouse, Todd M. [1 ]
Partridge, Kaitlyn J. [1 ,2 ]
Garrett, Patrick I. [3 ]
Honeycutt, Sarah C. [4 ]
Porter, Joseph H. [5 ,6 ]
机构
[1] Univ Wisconsin Green Bay, Dept Psychol, Green Bay, WI USA
[2] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI USA
[3] East Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USA
[4] Univ Buffalo, Dept Psychol, Buffalo, NY USA
[5] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA
[6] Northern Michigan, Dept Psychol Sci, Marquette, MI 49855 USA
来源
PLOS ONE | 2024年 / 19卷 / 04期
关键词
PRECLINICAL ASSAYS; KETAMINE; INHIBITION; ANALGESIA; MORPHINE;
D O I
10.1371/journal.pone.0301848
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Ketamine has been shown to produce analgesia in various acute and chronic pain states; however, abuse liability concerns have limited its utility. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) has been shown to produce antidepressant-like effects similar to ketamine without abuse liability concerns. (2R,6R)-HNK produces sustained analgesia in models of chronic pain, but has yet to be evaluated in models of acute pain. The present study evaluated the efficacy of acute (2R,6R)-HNK administration (one injection) in assays of pain-stimulated (52- and 56-degree hot plate test and acetic acid writhing) and pain-depressed behavior (locomotor activity and rearing) in male and female C57BL/6 mice. In assays of pain-stimulated behaviors, (2R,6R)-HNK (1-32 mg/kg) failed to produce antinociception in the 52- and 56-degree hot plate and acetic acid writhing assays. In assays of pain-depressed behaviors, 0.56% acetic acid produced a robust depression of locomotor activity and rearing that was not blocked by pretreatment of (2R,6R)-HNK (3.2-32 mg/kg). The positive controls morphine (hot plate test) and ketoprofen (acetic acid writhing, locomotor activity, and rearing) blocked pain-stimulated and pain-depressed behaviors. Finally, the effects of intermittent (2R,6R)-HNK administration were evaluated in 52-degree hot plate and pain-depressed locomotor activity and rearing. Intermittent administration of (2R,6R)-HNK also did not produce antinociceptive effects in the hot plate or pain-depressed locomotor activity assays. These results suggest that (2R,6R)-HNK is unlikely to have efficacy in treating acute pain; however, the efficacy of (2R,6R)-HNK in chronic pain states should continue to be evaluated.
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页数:16
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