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Participation of dorsal periaqueductal gray 5-HT1A receptors in the panicolytic-like effect of the κ-opioid receptor antagonist Nor-BNI.
Behav Brain Res. 2017 06 01; 327:75-82.BB

Abstract

Panic patients may have abnormalities in serotonergic and opioidergic neurotransmission. The dorsal periaqueductal gray (dPAG) plays an important role in organizing proximal defense, related to panic attacks. The 5-HT1A receptor (5-HT1A-R) is involved in regulating escape behavior that is organized in the dPAG. Activation of κ-opioid receptor (KOR) in this region causes anxiogenic effects. In this study, we investigated the involvement of KOR in regulating escape behavior, using systemic and intra-dPAG injection of the KOR antagonist Nor-BNI. As panic models, we used the elevated T-maze (ETM) and the dPAG electrical stimulation test (EST). We also evaluated whether activation of the 5-HT1A-R or the μ-opioid receptor (MOR) in the dPAG contributes to the Nor-BNI effects. The results showed that systemic administration of Nor-BNI, either subcutaneously (2.0 and 4.0mg/kg) or intraperitoneally (2.0mg/kg), impaired escape in the EST, indicating a panicolytic-like effect. Intra-dPAG injection of this antagonist (6.8nmol) caused the same effect in the EST and in the ETM. Association of ineffective doses of Nor-BNI and the 5-HT1A-R agonist 8-OH-DPAT caused panicolytic-like effect in these two tests. Previous administration of the 5-HT1A-R antagonist WAY-100635, but not of the MOR antagonist CTOP, blocked the panicolytic-like effect of Nor-BNI. These results indicate that KOR enhances proximal defense in the dPAG through 5-HT1A-R modulation, independently of MOR. Because former results indicate that the 5-HT1A-R is involved in the antipanic action of antidepressants, KOR antagonists may be useful as adjunctive or alternative drug treatment of panic disorder.

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Authors+Show Affiliations

Maraschin JC
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná 87020-900, Brazil. Electronic address: jhonatanmaraschin@gmail.com.
Almeida CB
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná 87020-900, Brazil.
Rangel MP
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná 87020-900, Brazil.
Roncon CM
Neurobiology of Emotions Research Centre (NAP-USP-NuPNE), School of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirao Preto, São Paulo 14049-900, Brazil; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil.
Sestile CC
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná 87020-900, Brazil.
Zangrossi H
Neurobiology of Emotions Research Centre (NAP-USP-NuPNE), School of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirao Preto, São Paulo 14049-900, Brazil; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil.
Graeff FG
Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, São Paulo 14050-220, Brazil; Neurobiology of Emotions Research Centre (NAP-USP-NuPNE), School of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirao Preto, São Paulo 14049-900, Brazil.
Audi EA
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná 87020-900, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, São Paulo 14050-220, Brazil. Electronic address: elisabethaudi8@gmail.com.

MeSH

8-Hydroxy-2-(di-n-propylamino)tetralinAnimalsDose-Response Relationship, DrugEscape ReactionMaleModels, AnimalNaltrexoneNarcotic AntagonistsPanicPeriaqueductal GrayPiperazinesPyridinesRats, WistarReceptor, Serotonin, 5-HT1AReceptors, Opioid, kappaReceptors, Opioid, muSerotonin 5-HT1 Receptor AgonistsSerotonin 5-HT1 Receptor AntagonistsSomatostatinTranquilizing Agents

Pub Type(s)

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

Language

eng

PubMed ID

28347824

Citation

Maraschin, Jhonatan Christian, et al. "Participation of Dorsal Periaqueductal Gray 5-HT1A Receptors in the Panicolytic-like Effect of the Κ-opioid Receptor Antagonist Nor-BNI." Behavioural Brain Research, vol. 327, 2017, pp. 75-82.
Maraschin JC, Almeida CB, Rangel MP, et al. Participation of dorsal periaqueductal gray 5-HT1A receptors in the panicolytic-like effect of the κ-opioid receptor antagonist Nor-BNI. Behav Brain Res. 2017;327:75-82.
Maraschin, J. C., Almeida, C. B., Rangel, M. P., Roncon, C. M., Sestile, C. C., Zangrossi, H., Graeff, F. G., & Audi, E. A. (2017). Participation of dorsal periaqueductal gray 5-HT1A receptors in the panicolytic-like effect of the κ-opioid receptor antagonist Nor-BNI. Behavioural Brain Research, 327, 75-82. https://doi.org/10.1016/j.bbr.2017.03.033
Maraschin JC, et al. Participation of Dorsal Periaqueductal Gray 5-HT1A Receptors in the Panicolytic-like Effect of the Κ-opioid Receptor Antagonist Nor-BNI. Behav Brain Res. 2017 06 1;327:75-82. PubMed PMID: 28347824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Participation of dorsal periaqueductal gray 5-HT1A receptors in the panicolytic-like effect of the κ-opioid receptor antagonist Nor-BNI. AU - Maraschin,Jhonatan Christian, AU - Almeida,Camila Biesdorf, AU - Rangel,Marcel Pereira, AU - Roncon,Camila Marroni, AU - Sestile,Caio César, AU - Zangrossi,Hélio,Jr AU - Graeff,Frederico Guilherme, AU - Audi,Elisabeth Aparecida, Y1 - 2017/03/24/ PY - 2016/12/06/received PY - 2017/03/15/revised PY - 2017/03/21/accepted PY - 2017/3/30/pubmed PY - 2017/12/20/medline PY - 2017/3/29/entrez KW - 8-OH-DPAT hydrobromide (PubChem CID: 6917794) KW - CTOP (PubChem CID: 5311058) KW - Dorsal periaqueductal gray KW - Elevated T-maze KW - Panic disorder KW - WAY-100635 maleate salt (PubChem CID: 11957721) KW - dPAG electrical stimulation KW - nor-binaltorphimine dihydrochloride (PubChem CID: 11957626) KW - κ-opioid receptor 5-HT(1A) receptor SP - 75 EP - 82 JF - Behavioural brain research JO - Behav Brain Res VL - 327 N2 - Panic patients may have abnormalities in serotonergic and opioidergic neurotransmission. The dorsal periaqueductal gray (dPAG) plays an important role in organizing proximal defense, related to panic attacks. The 5-HT1A receptor (5-HT1A-R) is involved in regulating escape behavior that is organized in the dPAG. Activation of κ-opioid receptor (KOR) in this region causes anxiogenic effects. In this study, we investigated the involvement of KOR in regulating escape behavior, using systemic and intra-dPAG injection of the KOR antagonist Nor-BNI. As panic models, we used the elevated T-maze (ETM) and the dPAG electrical stimulation test (EST). We also evaluated whether activation of the 5-HT1A-R or the μ-opioid receptor (MOR) in the dPAG contributes to the Nor-BNI effects. The results showed that systemic administration of Nor-BNI, either subcutaneously (2.0 and 4.0mg/kg) or intraperitoneally (2.0mg/kg), impaired escape in the EST, indicating a panicolytic-like effect. Intra-dPAG injection of this antagonist (6.8nmol) caused the same effect in the EST and in the ETM. Association of ineffective doses of Nor-BNI and the 5-HT1A-R agonist 8-OH-DPAT caused panicolytic-like effect in these two tests. Previous administration of the 5-HT1A-R antagonist WAY-100635, but not of the MOR antagonist CTOP, blocked the panicolytic-like effect of Nor-BNI. These results indicate that KOR enhances proximal defense in the dPAG through 5-HT1A-R modulation, independently of MOR. Because former results indicate that the 5-HT1A-R is involved in the antipanic action of antidepressants, KOR antagonists may be useful as adjunctive or alternative drug treatment of panic disorder. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/28347824/Participation_of_dorsal_periaqueductal_gray_5_HT1A_receptors_in_the_panicolytic_like_effect_of_the_κ_opioid_receptor_antagonist_Nor_BNI_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(16)31211-6 DB - PRIME DP - Unbound Medicine ER -
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