NOP agonists prevent the antidepressant-like effects of nortriptyline and fluoxetine but not R-ketamine.
Victor A D Holanda, Wilton B Santos, Laila Asth, Remo Guerrini, Girolamo Calo', Chiara Ruzza, Elaine C Gavioli
Psychopharmacology November 2018 DOI: 10.1007/s00213-018-5004-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Male Swiss mice |
| Interventions | N/OFQ Ro 65-6570 nortriptyline fluoxetine R-ketamine SB-612111 |
| Topics | Esketamine Ketamine |
| Keywords | Antidepressants Forced swimming test Learned helplessness Mouse Nop receptor Nociceptin/orphanin fq |
| Key findings | NOP receptor agonists (N/OFQ and Ro 65-6570) alone produced no behavioral change, but co-administration blocked the antidepressant-like effects of SB-612111, fluoxetine, and nortriptyline in the forced swimming test, while R-ketamine's effects were not blocked. In the learned helplessness model, Ro 65-6570 blocked SB-612111 and nortriptyline effects but not R-ketamine. The authors conclude that NOP receptor activation inhibits the acute antidepressant effects of nortriptyline and fluoxetine, but not R-ketamine. |
Abstract
Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of a Gi protein-coupled receptor named NOP. Both N/OFQ and NOP receptor are widely expressed in brain areas involved in the control of emotional processes. Clinical and preclinical studies support antidepressant effects due to the blockade of NOP receptor signaling. By contrast, NOP receptor activation did not evoke any change in behavioral despair tests. The present study aimed to investigate the effects of the co-administration of NOP agonists and classic antidepressant drugs in the forced swimming test (FST) and learned helplessness model (LH) in mice. Male Swiss mice were co-administered with NOP agonists (N/OFQ and Ro 65-6570) and antidepressants (nortriptyline, fluoxetine, and R-ketamine) or SB-612111 (NOP antagonist) and the behavioral effects were assessed in the FST and LH tests. Fluoxetine, nortriptyline, R-ketamine and the NOP antagonist SB-612111 displayed antidepressant-like effects in the FST. The administration of the NOP agonists N/OFQ and Ro 65-6570 did not induce any behavioral change. However, co-administration of NOP agonists blocked the antidepressant effects of SB-612111, fluoxetine, and nortriptyline, but not R-ketamine in the FST. Similarly, in the LH, the systemic injection of SB-612111, nortriptyline, and R-ketamine reversed helplessness. The co-administration of Ro 65-6570 blocked the antidepressant-like effects of SB-612111 and nortriptyline, but not R-ketamine. NOP receptor activation inhibits the acute antidepressant effects of nortriptyline and fluoxetine, but not R-ketamine. The present findings contribute to further understand the role played by the N/OFQ-NOP receptor system in regulating mood states.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 3
- Differential effects of opioid receptor antagonism on the anti-dyskinetic and anti-parkinsonian effects of sub-anesthetic ketamine treatment in a preclinical model. Neuropharmacology October 1, 2024
- Ketamine Reduces Avoidance Responses During Re-Exposition to Aversive Stimulus: Comparison Between (S)-Isomer and Racemic Mixture. Brain Sciences December 22, 2024
- Contribution of the opioid system to depression and to the therapeutic effects of classical antidepressants and ketamine. Life Science May 1, 2023
Cites 6
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- 5-Hydroxytryptamine-Independent Antidepressant Actions of (R)-Ketamine in a Chronic Social Defeat Stress Model The International Journal of Neuropsychopharmacology November 15, 2017
- S-Ketamine Mediates Its Acute and Sustained Antidepressant-Like Activity through a 5-HT1B Receptor Dependent Mechanism in a Genetic Rat Model of Depression Frontiers in Pharmacology January 15, 2018
- NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses Nature June 15, 2011
and 1 more in the library