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Modulation of the NOP receptor signaling affects resilience to acute stress.
- Source :
-
Journal of psychopharmacology (Oxford, England) [J Psychopharmacol] 2019 Dec; Vol. 33 (12), pp. 1540-1549. Date of Electronic Publication: 2019 Jul 24. - Publication Year :
- 2019
-
Abstract
- Background: The peptide nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are implicated in the modulation of emotional states. Previous human and rodent findings support NOP antagonists as antidepressants. However, the role played by the N/OFQ-NOP receptor system in resilience to stress is unclear.<br />Aims: The present study investigated the effects of activation or blockade of NOP receptor signaling before exposure to acute stress.<br />Methods: The behavioral effects of the administration before stress of the NOP agonists Ro 65-6570 (0.01-1 mg/kg) and MCOPPB (0.1-10 mg/kg), and the NOP antagonist SB-612111 (1-10 mg/kg) were assessed in mice exposed to inescapable electric footshock and forced swim as stressors. The behavioral phenotype of mice lacking the NOP receptor (NOP(-/-)) exposed to inescapable electric footshock was also investigated.<br />Results: The activation of NOP receptor signaling with the agonists increased the percentage of mice developing helpless behavior and facilitated immobile posture. In contrast, the blockade of NOP receptor reduced the acquisition of depressive-like phenotypes, and similar resistance to develop helpless behaviors was observed in NOP(-/-) mice. Under the same stressful conditions, the antidepressant nortriptyline (20 mg/kg) did not change the acquisition of helpless behavior and immobile posture.<br />Conclusions: These findings support the view that NOP activation during acute stress facilitates the development of depressive-related behaviors, whereas NOP blockade has a protective outcome. This study showed for first time that NOP antagonists are worthy of investigation as preemptive treatments in patients with severe risk factors for depression.
- Subjects :
- Animals
Behavior, Animal drug effects
Benzimidazoles administration & dosage
Benzimidazoles pharmacology
Cycloheptanes administration & dosage
Cycloheptanes pharmacology
Depression drug therapy
Depression physiopathology
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Imidazoles administration & dosage
Imidazoles pharmacology
Male
Mice
Mice, Knockout
Nortriptyline pharmacology
Piperidines administration & dosage
Piperidines pharmacology
Receptors, Opioid drug effects
Receptors, Opioid genetics
Spiro Compounds administration & dosage
Spiro Compounds pharmacology
Stress, Psychological physiopathology
Nociceptin Receptor
Nociceptin
Opioid Peptides metabolism
Receptors, Opioid metabolism
Resilience, Psychological drug effects
Stress, Psychological drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1461-7285
- Volume :
- 33
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of psychopharmacology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 31337258
- Full Text :
- https://doi.org/10.1177/0269881119864942