Effects of (2R,6R)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice
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Hillhouse, Todd M.
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Univ Wisconsin Green Bay, Dept Psychol, Green Bay, WI USAUniv Wisconsin Green Bay, Dept Psychol, Green Bay, WI USA
Hillhouse, Todd M.
[1
]
Partridge, Kaitlyn J.
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Univ Wisconsin Green Bay, Dept Psychol, Green Bay, WI USA
Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI USAUniv Wisconsin Green Bay, Dept Psychol, Green Bay, WI USA
Partridge, Kaitlyn J.
[1
,2
]
Garrett, Patrick I.
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East Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USAUniv Wisconsin Green Bay, Dept Psychol, Green Bay, WI USA
Garrett, Patrick I.
[3
]
Honeycutt, Sarah C.
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Univ Buffalo, Dept Psychol, Buffalo, NY USAUniv Wisconsin Green Bay, Dept Psychol, Green Bay, WI USA
Honeycutt, Sarah C.
[4
]
Porter, Joseph H.
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Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA
Northern Michigan, Dept Psychol Sci, Marquette, MI 49855 USAUniv Wisconsin Green Bay, Dept Psychol, Green Bay, WI USA
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
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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[11]
Hillhouse Todd M, 2021, J Pharmacol Exp Ther, V378, P287, DOI 10.1124/jpet.121.000524
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Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Calif State Univ Hayward, Dept Psychol, Hayward, CA 94542 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Kandasamy, Ram
Hillhouse, Todd M.
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Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Univ Wisconsin, Dept Psychol, Green Bay, WI 54311 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Hillhouse, Todd M.
Livingston, Kathryn E.
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h-index: 0
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Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Probe Life, Palo Alto, CA 94303 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Livingston, Kathryn E.
Kochan, Kelsey E.
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Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Kochan, Kelsey E.
Meurice, Claire
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机构:
Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Meurice, Claire
Eans, Shainnel O.
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Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Eans, Shainnel O.
Li, Ming-Hua
论文数: 0引用数: 0
h-index: 0
机构:
Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA
Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Li, Ming-Hua
White, Andrew D.
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Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
White, Andrew D.
Roques, Bernard P.
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Univ Paris 05, Unite Technol Chim & Biol Sante, Paris 05, FranceUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Roques, Bernard P.
McLaughlin, Jay P.
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机构:
Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
McLaughlin, Jay P.
Ingram, Susan L.
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机构:
Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Ingram, Susan L.
Burford, Neil T.
论文数: 0引用数: 0
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Bristol Myers Squibb, Lead Discovery & Optimizat, Wallingford, CT 06492 USA
PRA Hlth Sci, Strateg Solut Div, Raleigh, NC 27612 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Burford, Neil T.
Alt, Andrew
论文数: 0引用数: 0
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机构:
Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Bristol Myers Squibb, Lead Discovery & Optimizat, Wallingford, CT 06492 USA
Univ Michigan, Life Sci Inst, Ctr Chem Genom, Ann Arbor, MI 48109 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Alt, Andrew
Traynor, John R.
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Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
机构:
Calif State Univ, Dept Psychol, 25800 Carlos Bee Blvd,Sci S229, Hayward, CA 94560 USACalif State Univ, Dept Psychol, 25800 Carlos Bee Blvd,Sci S229, Hayward, CA 94560 USA
Kandasamy, Ram
Morgan, Michael M.
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Washington State Univ, Dept Psychol, Vancouver, WA USACalif State Univ, Dept Psychol, 25800 Carlos Bee Blvd,Sci S229, Hayward, CA 94560 USA
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Harvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USAHarvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA
Kawai, Kosuke
Kawai, Alison Tse
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Harvard Med Sch, Dept Populat Med, Boston, MA USA
Harvard Pilgrim Hlth Care Inst, Boston, MA USAHarvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA
Kawai, Alison Tse
Wollan, Peter
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Olmsted Med Ctr, Dept Res, Rochester, MN USAHarvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA
Wollan, Peter
Yawn, Barbara P.
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h-index: 0
机构:
Olmsted Med Ctr, Dept Res, Rochester, MN USA
Univ Minnesota, Minneapolis, MN USAHarvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA
机构:
Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Calif State Univ Hayward, Dept Psychol, Hayward, CA 94542 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Kandasamy, Ram
Hillhouse, Todd M.
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h-index: 0
机构:
Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Univ Wisconsin, Dept Psychol, Green Bay, WI 54311 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Hillhouse, Todd M.
Livingston, Kathryn E.
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h-index: 0
机构:
Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Probe Life, Palo Alto, CA 94303 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Livingston, Kathryn E.
Kochan, Kelsey E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Kochan, Kelsey E.
Meurice, Claire
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Meurice, Claire
Eans, Shainnel O.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Eans, Shainnel O.
Li, Ming-Hua
论文数: 0引用数: 0
h-index: 0
机构:
Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA
Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Li, Ming-Hua
White, Andrew D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
White, Andrew D.
Roques, Bernard P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Paris 05, Unite Technol Chim & Biol Sante, Paris 05, FranceUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Roques, Bernard P.
McLaughlin, Jay P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
McLaughlin, Jay P.
Ingram, Susan L.
论文数: 0引用数: 0
h-index: 0
机构:
Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Ingram, Susan L.
Burford, Neil T.
论文数: 0引用数: 0
h-index: 0
机构:
Bristol Myers Squibb, Lead Discovery & Optimizat, Wallingford, CT 06492 USA
PRA Hlth Sci, Strateg Solut Div, Raleigh, NC 27612 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Burford, Neil T.
Alt, Andrew
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Bristol Myers Squibb, Lead Discovery & Optimizat, Wallingford, CT 06492 USA
Univ Michigan, Life Sci Inst, Ctr Chem Genom, Ann Arbor, MI 48109 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Alt, Andrew
Traynor, John R.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USAUniv Michigan, Med Sch, Dept Pharmacol, Edward F Domino Res Ctr, Ann Arbor, MI 48109 USA
机构:
Calif State Univ, Dept Psychol, 25800 Carlos Bee Blvd,Sci S229, Hayward, CA 94560 USACalif State Univ, Dept Psychol, 25800 Carlos Bee Blvd,Sci S229, Hayward, CA 94560 USA
Kandasamy, Ram
Morgan, Michael M.
论文数: 0引用数: 0
h-index: 0
机构:
Washington State Univ, Dept Psychol, Vancouver, WA USACalif State Univ, Dept Psychol, 25800 Carlos Bee Blvd,Sci S229, Hayward, CA 94560 USA
机构:
Harvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USAHarvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA
Kawai, Kosuke
Kawai, Alison Tse
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Med Sch, Dept Populat Med, Boston, MA USA
Harvard Pilgrim Hlth Care Inst, Boston, MA USAHarvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA
Kawai, Alison Tse
Wollan, Peter
论文数: 0引用数: 0
h-index: 0
机构:
Olmsted Med Ctr, Dept Res, Rochester, MN USAHarvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA
Wollan, Peter
Yawn, Barbara P.
论文数: 0引用数: 0
h-index: 0
机构:
Olmsted Med Ctr, Dept Res, Rochester, MN USA
Univ Minnesota, Minneapolis, MN USAHarvard Med Sch, Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA