Biological psychiatry · 2022
Mu Opioid Receptor Activation Mediates (S)-ketamine Reinforcement in Rats: Implications for Abuse Liability.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод в очереди
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Levinstein Marjorie R, Carlton Meghan L, Di Ianni Tommaso, Ventriglia Emilya N, Rizzo Arianna, Gomez Juan L, Budinich Reece C, Shaham Yavin, Airan Raag D, Zarate Carlos A, Bonaventura Jordi, Michaelides Michael
Аннотация
BACKGROUND: (S)-ketamine is an NMDA receptor antagonist, but it also binds to and activates mu opioid receptors (MORs) and kappa opioid receptors in vitro. However, the extent to which these receptors contribute to (S)-ketamine's in vivo pharmacology is unknown.
METHODS: We investigated the extent to which (S)-ketamine interacts with opioid receptors in rats by combining in vitro and in vivo pharmacological approaches, in vivo molecular and functional imaging, and behavioral procedures relevant to human abuse liability.
RESULTS: We found that the preferential opioid receptor antagonist naltrexone decreased (S)-ketamine self-administration and (S)-ketamine-induced activation of the nucleus accumbens, a key brain reward region. A single reinforcing dose of (S)-ketamine occupied brain MORs in vivo, and repeated doses decreased MOR density and activity and decreased heroin reinforcement without producing changes in NMDA receptor or kappa opioid receptor density.
CONCLUSIONS: These results suggest that (S)-ketamine's abuse liability in humans is mediated in part by brain MORs.
METHODS: We investigated the extent to which (S)-ketamine interacts with opioid receptors in rats by combining in vitro and in vivo pharmacological approaches, in vivo molecular and functional imaging, and behavioral procedures relevant to human abuse liability.
RESULTS: We found that the preferential opioid receptor antagonist naltrexone decreased (S)-ketamine self-administration and (S)-ketamine-induced activation of the nucleus accumbens, a key brain reward region. A single reinforcing dose of (S)-ketamine occupied brain MORs in vivo, and repeated doses decreased MOR density and activity and decreased heroin reinforcement without producing changes in NMDA receptor or kappa opioid receptor density.
CONCLUSIONS: These results suggest that (S)-ketamine's abuse liability in humans is mediated in part by brain MORs.