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Interaction between μ-opioid and 5-HT1A receptors in the regulation of panic-related defensive responses in the rat dorsal periaqueductal grey.
J Psychopharmacol. 2014 Dec; 28(12):1155-60.JP

Abstract

A wealth of evidence indicates that the activation of 5-HT1A and 5-HT2A receptors in the dorsal periaqueductal grey matter (dPAG) inhibits escape, a panic-related defensive behaviour. Results that were previously obtained with the elevated T-maze test of anxiety/panic suggest that 5-HT1A and μ-opioid receptors in this midbrain area work together to regulate this response. To investigate the generality of this finding, we assessed whether the same cooperative mechanism is engaged when escape is evoked by a different aversive stimulus electrical stimulation of the dPAG. Administration of the μ-receptor blocker CTOP into the dPAG did not change the escape threshold, but microinjection of the μ-receptor agonist DAMGO (0.3 and 0.5 nmol) or the 5-HT1A receptor agonist 8-OHDPAT (1.6 nmol) increased this index, indicating a panicolytic-like effect. Pretreatment with CTOP antagonised the anti-escape effect of 8-OHDPAT. Additionally, combined administration of subeffective doses of DAMGO and 8-OHDPAT increased the escape threshold, indicating drug synergism. Therefore, regardless of the aversive nature of the stimulus, μ-opioid and 5-HT1A receptors cooperatively act to regulate escape behaviour. A better comprehension of this mechanism might allow for new therapeutic strategies for panic disorder.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Rangel MP
Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil.
Zangrossi H
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil NAP-NuPNE - Neurobiology of Emotion Research Centre, University of São Paulo, Ribeirão Preto, Brazil.
Roncon CM
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil.
Graeff FG
INeC - Institute of Behavioral Neuroscience, Ribeirão Preto, Brazil NAP-NuPNE - Neurobiology of Emotion Research Centre, University of São Paulo, Ribeirão Preto, Brazil.
Audi EA
Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil INeC - Institute of Behavioral Neuroscience, Ribeirão Preto, Brazil elisabethaudi8@gmail.com.

MeSH

8-Hydroxy-2-(di-n-propylamino)tetralinAnimalsElectric StimulationEnkephalin, Ala(2)-MePhe(4)-Gly(5)-Escape ReactionMaleMicroinjectionsPanicPeriaqueductal GrayRatsReceptor, Serotonin, 5-HT1AReceptor, Serotonin, 5-HT2AReceptors, Opioid, muSomatostatin

Pub Type(s)

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

Language

eng

PubMed ID

25315826

Citation

Rangel, Marcel P., et al. "Interaction Between Μ-opioid and 5-HT1A Receptors in the Regulation of Panic-related Defensive Responses in the Rat Dorsal Periaqueductal Grey." Journal of Psychopharmacology (Oxford, England), vol. 28, no. 12, 2014, pp. 1155-60.
Rangel MP, Zangrossi H, Roncon CM, et al. Interaction between μ-opioid and 5-HT1A receptors in the regulation of panic-related defensive responses in the rat dorsal periaqueductal grey. J Psychopharmacol. 2014;28(12):1155-60.
Rangel, M. P., Zangrossi, H., Roncon, C. M., Graeff, F. G., & Audi, E. A. (2014). Interaction between μ-opioid and 5-HT1A receptors in the regulation of panic-related defensive responses in the rat dorsal periaqueductal grey. Journal of Psychopharmacology (Oxford, England), 28(12), 1155-60. https://doi.org/10.1177/0269881114554274
Rangel MP, et al. Interaction Between Μ-opioid and 5-HT1A Receptors in the Regulation of Panic-related Defensive Responses in the Rat Dorsal Periaqueductal Grey. J Psychopharmacol. 2014;28(12):1155-60. PubMed PMID: 25315826.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction between μ-opioid and 5-HT1A receptors in the regulation of panic-related defensive responses in the rat dorsal periaqueductal grey. AU - Rangel,Marcel P, AU - Zangrossi,Hélio,Jr AU - Roncon,Camila M, AU - Graeff,Frederico G, AU - Audi,Elisabeth A, Y1 - 2014/10/14/ PY - 2014/10/16/entrez PY - 2014/10/16/pubmed PY - 2015/12/24/medline KW - 5-HT1A receptor KW - Panic KW - dorsal periaqueductal grey KW - μ-opioid receptor SP - 1155 EP - 60 JF - Journal of psychopharmacology (Oxford, England) JO - J Psychopharmacol VL - 28 IS - 12 N2 - A wealth of evidence indicates that the activation of 5-HT1A and 5-HT2A receptors in the dorsal periaqueductal grey matter (dPAG) inhibits escape, a panic-related defensive behaviour. Results that were previously obtained with the elevated T-maze test of anxiety/panic suggest that 5-HT1A and μ-opioid receptors in this midbrain area work together to regulate this response. To investigate the generality of this finding, we assessed whether the same cooperative mechanism is engaged when escape is evoked by a different aversive stimulus electrical stimulation of the dPAG. Administration of the μ-receptor blocker CTOP into the dPAG did not change the escape threshold, but microinjection of the μ-receptor agonist DAMGO (0.3 and 0.5 nmol) or the 5-HT1A receptor agonist 8-OHDPAT (1.6 nmol) increased this index, indicating a panicolytic-like effect. Pretreatment with CTOP antagonised the anti-escape effect of 8-OHDPAT. Additionally, combined administration of subeffective doses of DAMGO and 8-OHDPAT increased the escape threshold, indicating drug synergism. Therefore, regardless of the aversive nature of the stimulus, μ-opioid and 5-HT1A receptors cooperatively act to regulate escape behaviour. A better comprehension of this mechanism might allow for new therapeutic strategies for panic disorder. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/25315826/Interaction_between_μ_opioid_and_5_HT1A_receptors_in_the_regulation_of_panic_related_defensive_responses_in_the_rat_dorsal_periaqueductal_grey_ DB - PRIME DP - Unbound Medicine ER -