Tags

Type your tag names separated by a space and hit enter

Nociceptin/orphanin FQ receptor agonists increase aggressiveness in the mouse resident-intruder test.
Behav Brain Res. 2019 01 01; 356:120-126.BB

Abstract

Aggressive behaviors can be considered symptoms of bipolar disorder, schizophrenia, post-traumatic stress, intermittent explosive, and personality disorders. Nociceptin/orphanin FQ (N/OFQ) is a peptide acting as endogenous ligand of the NOP receptor. Preclinical and clinical findings suggest the NOP receptor as an innovative target for the treatment of psychopathologies, such as anxiety, depression, and drug abuse. This study investigated the effects of NOP ligands and the behavioral phenotype of mice lacking the NOP receptor in an animal model of aggressiveness, the resident-intruder test. Mood stabilizers, such as valproate, lithium, and carbamazepine reduced aggressive behaviors of resident mice, while diazepam was inactive. In contrast, para-chlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis, increased aggressiveness in mice. Similar to PCPA, the treatment with the NOP agonists Ro 65-6570 and AT-090 also increased aggressive behaviors. The systemic administration of the NOP antagonist SB-612111 did not modify the behavior of resident mice, but it prevented the aggressive behavior of Ro 65-6570. NOP receptor knockout mice did not display any behavioral difference compared to wild-type animals in the resident-intruder test. None of the treatments affected non-agonistic behaviors and spontaneous locomotion. In conclusion, NOP receptor agonists increased aggressiveness, while the pharmacological and genetic blockade of NOP receptor signaling did not modify agonistic behaviors. Ultimately, the aggressive profile of action of NOP agonists should be taken into account in the development of innovative psychiatric drugs targeting the NOP receptor.

Authors+Show Affiliations

Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.Astraea Therapeutics, LLC., 320 Logue Avenue, Mountain View, CA, 94043, United States.Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.Department of Medical Sciences, Section of Pharmacology, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.Department of Medical Sciences, Section of Pharmacology, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil. Electronic address: egavioli@hotmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30142397

Citation

Silva, Epifanio F., et al. "Nociceptin/orphanin FQ Receptor Agonists Increase Aggressiveness in the Mouse Resident-intruder Test." Behavioural Brain Research, vol. 356, 2019, pp. 120-126.
Silva EF, Silva AI, Asth L, et al. Nociceptin/orphanin FQ receptor agonists increase aggressiveness in the mouse resident-intruder test. Behav Brain Res. 2019;356:120-126.
Silva, E. F., Silva, A. I., Asth, L., Souza, L. S., Zaveri, N. T., Guerrini, R., Calo', G., Ruzza, C., & Gavioli, E. C. (2019). Nociceptin/orphanin FQ receptor agonists increase aggressiveness in the mouse resident-intruder test. Behavioural Brain Research, 356, 120-126. https://doi.org/10.1016/j.bbr.2018.08.019
Silva EF, et al. Nociceptin/orphanin FQ Receptor Agonists Increase Aggressiveness in the Mouse Resident-intruder Test. Behav Brain Res. 2019 01 1;356:120-126. PubMed PMID: 30142397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nociceptin/orphanin FQ receptor agonists increase aggressiveness in the mouse resident-intruder test. AU - Silva,Epifanio F, AU - Silva,Aldemara I, AU - Asth,Laila, AU - Souza,Lisiane S, AU - Zaveri,Nurulain T, AU - Guerrini,Remo, AU - Calo',Girolamo, AU - Ruzza,Chiara, AU - Gavioli,Elaine C, Y1 - 2018/08/22/ PY - 2018/04/19/received PY - 2018/07/27/revised PY - 2018/08/20/accepted PY - 2018/8/25/pubmed PY - 2019/3/23/medline PY - 2018/8/25/entrez KW - Aggressiveness KW - Mouse KW - NOP knockout mice KW - NOP ligands KW - NOP receptor KW - Resident-intruder test SP - 120 EP - 126 JF - Behavioural brain research JO - Behav. Brain Res. VL - 356 N2 - Aggressive behaviors can be considered symptoms of bipolar disorder, schizophrenia, post-traumatic stress, intermittent explosive, and personality disorders. Nociceptin/orphanin FQ (N/OFQ) is a peptide acting as endogenous ligand of the NOP receptor. Preclinical and clinical findings suggest the NOP receptor as an innovative target for the treatment of psychopathologies, such as anxiety, depression, and drug abuse. This study investigated the effects of NOP ligands and the behavioral phenotype of mice lacking the NOP receptor in an animal model of aggressiveness, the resident-intruder test. Mood stabilizers, such as valproate, lithium, and carbamazepine reduced aggressive behaviors of resident mice, while diazepam was inactive. In contrast, para-chlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis, increased aggressiveness in mice. Similar to PCPA, the treatment with the NOP agonists Ro 65-6570 and AT-090 also increased aggressive behaviors. The systemic administration of the NOP antagonist SB-612111 did not modify the behavior of resident mice, but it prevented the aggressive behavior of Ro 65-6570. NOP receptor knockout mice did not display any behavioral difference compared to wild-type animals in the resident-intruder test. None of the treatments affected non-agonistic behaviors and spontaneous locomotion. In conclusion, NOP receptor agonists increased aggressiveness, while the pharmacological and genetic blockade of NOP receptor signaling did not modify agonistic behaviors. Ultimately, the aggressive profile of action of NOP agonists should be taken into account in the development of innovative psychiatric drugs targeting the NOP receptor. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/30142397/Nociceptin/orphanin_FQ_receptor_agonists_increase_aggressiveness_in_the_mouse_resident_intruder_test_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(18)30567-9 DB - PRIME DP - Unbound Medicine ER -