Opioid system is necessary but not sufficient for antidepressive actions of ketamine in rodents

@article{Klein2020OpioidSI,
  title={Opioid system is necessary but not sufficient for antidepressive actions of ketamine in rodents},
  author={Matthew E. Klein and Joshua Chandra and Salma Sheriff and R. Malinow},
  journal={Proceedings of the National Academy of Sciences},
  year={2020},
  volume={117},
  pages={2656 - 2662}
}
Significance Ketamine, an NMDA receptor antagonist, has generated intense excitement as a therapy for treatment-resistant depression. However, ketamine and its metabolites can act on a wide range of targets, including opioid receptors, which has raised concerns. Using behavioral and cellular assays in rodents, we find that blocking opioid function prevents the antidepressant-like effects of ketamine. However, in contrast to ketamine, administration of a µ-opioid agonist is hedonic and… Expand
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References

SHOWING 1-10 OF 87 REFERENCES
NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses
TLDR
It is shown that ketamine and other NMDAR antagonists produce fast-acting behavioural antidepressant-like effects in mouse models, and that these effects depend on the rapid synthesis of brain-derived neurotrophic factor, suggesting the regulation of protein synthesis by spontaneous neurotransmission may serve as a viable therapeutic target for the development of fast- acting antidepressants. Expand
Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review
TLDR
Current efforts are focused on extending ketamine’s antidepressant efficacy, uncovering the neurobiological mechanisms responsible for ketamine's antidepressant activity in biologically enriched subgroups, and identifying treatment response biomarkers to personalize antidepressant selection. Expand
Central antinociception induced by ketamine is mediated by endogenous opioids and μ- and δ-opioid receptors
TLDR
Evidence is provided for the involvement of endogenous opioids and μ- and δ-opioid receptors in ketamine-induced central antinociception, which is generally believed that NMDA receptor antagonism accounts for most of the anesthetic and analgesic effects of ketamine. Expand
Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms
TLDR
Pharmacological target deconvolution of ketamine and its metabolites will provide insight critical to the development of new pharmacotherapies that possess the desirable clinical effects of ketamines, but limit undesirable side effects. Expand
The Involvement of the &mgr;-Opioid Receptor in Ketamine-Induced Respiratory Depression and Antinociception
TLDR
Results indicate that at supraspinal sites S(+) ketamine interacts with the &mgr;-opioid system, and this interaction contributes significantly to S(+ ketamine-induced respiratory depression and suPRaspinal antinociception. Expand
Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.
TLDR
The findings suggest that ketamine's acute antidepressant effect requires opioid system activation, and the dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects ofketamine in adults with treatment-resistant depression. Expand
Opiate Receptor Mediation of Ketamine Analgesia
TLDR
In vivo, the authors found that ketamine displaces 3H-etorphine, a potent narcotic, from opiate receptors in regional areas of the mouse brain, especially in the thalamic region, but not in the cortex, suggesting that a significant mechanism of ketamine-induced analgesia is mediated by opiates receptors. Expand
Ketamine blocks bursting in the lateral habenula to rapidly relieve depression
TLDR
It is shown that blockade of NMDAR-dependent bursting activity in the ‘anti-reward center’, the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. Expand
Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism
TLDR
Results indicate that opioid receptor activation plays a significant role in the antisuicidality effects of ketamine, and naltrexone attenuates the antisUicidalities effects ofketamine on all three suicidability scales/subscales. Expand
NMDA and opioid receptors: their interactions in antinociception, tolerance and neuroplasticity
  • J. Mao
  • Medicine
  • Brain Research Reviews
  • 1999
TLDR
Emerging evidence indicates that activation of NMDA receptors may differentially modulate functions mediated by distinct opioid receptor subtypes, namely mu, delta, and kappa receptors. Expand
...
1
2
3
4
5
...