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Cooperative regulation of anxiety and panic-related defensive behaviors in the rat periaqueductal grey matter by 5-HT1A and μ-receptors.
J Psychopharmacol 2013; 27(12):1141-8JP

Abstract

Previous results with the elevated T-maze (ETM) test indicate that the antipanic action of serotonin (5-HT) in the dorsal periaqueductal grey (dPAG) depends on the activation endogenous opioid peptides. The aim of the present work was to investigate the interaction between opioid- and serotonin-mediated neurotransmission in the modulation of defensive responses in rats submitted to the ETM. The obtained results showed that intra-dPAG administration of morphine significantly increased escape latency, a panicolytic-like effect that was blocked by pre-treatment with intra-dPAG injection of either naloxone or the 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1 piperazinyl] ethyl] -N- 2- pyridinyl-ciclohexanecarboxamide maleate (WAY-100635). In addition, previous administration of naloxone antagonized both the anti-escape and the anti-avoidance (anxiolytic-like) effect of the 5-HT1A agonist (±)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), but did not affect the anti-escape effect of the 5-HT2A agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI). Moreover, the combination of sub-effective doses of locally administered 5-HT and morphine significantly impaired ETM escape performance. Finally, the µ-antagonist D-PHE-CYS-TYR-D-TRP-ORN-THR-PEN (CTOP) blocked the anti-avoidance as well as the anti-escape effect of 8-OHDPAT, and the association of sub-effective doses of the µ-opioid receptor agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin acetate salt (DAMGO) and of 8-OHDPAT had anti-escape and anti-avoidance effects in the ETM. These results suggest a synergic interaction between the 5-HT1A and the µ-opioid receptor at post-synaptic level on neurons of the dPAG that regulate proximal defense, theoretically related to panic attacks.

Authors+Show Affiliations

1Department of Pharmacology and Therapeutics, State University of Maringá, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23598399

Citation

Roncon, Camila M., et al. "Cooperative Regulation of Anxiety and Panic-related Defensive Behaviors in the Rat Periaqueductal Grey Matter By 5-HT1A and Μ-receptors." Journal of Psychopharmacology (Oxford, England), vol. 27, no. 12, 2013, pp. 1141-8.
Roncon CM, Biesdorf C, Coimbra NC, et al. Cooperative regulation of anxiety and panic-related defensive behaviors in the rat periaqueductal grey matter by 5-HT1A and μ-receptors. J Psychopharmacol (Oxford). 2013;27(12):1141-8.
Roncon, C. M., Biesdorf, C., Coimbra, N. C., Audi, E. A., Zangrossi, H., & Graeff, F. G. (2013). Cooperative regulation of anxiety and panic-related defensive behaviors in the rat periaqueductal grey matter by 5-HT1A and μ-receptors. Journal of Psychopharmacology (Oxford, England), 27(12), pp. 1141-8. doi:10.1177/0269881113485144.
Roncon CM, et al. Cooperative Regulation of Anxiety and Panic-related Defensive Behaviors in the Rat Periaqueductal Grey Matter By 5-HT1A and Μ-receptors. J Psychopharmacol (Oxford). 2013;27(12):1141-8. PubMed PMID: 23598399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cooperative regulation of anxiety and panic-related defensive behaviors in the rat periaqueductal grey matter by 5-HT1A and μ-receptors. AU - Roncon,Camila M, AU - Biesdorf,Carla, AU - Coimbra,Norberto C, AU - Audi,Elisabeth A, AU - Zangrossi,Hélio,Jr AU - Graeff,Frederico G, Y1 - 2013/04/17/ PY - 2013/4/20/entrez PY - 2013/4/20/pubmed PY - 2015/1/28/medline KW - 5-HT1A receptor KW - Serotonin KW - elevated T-maze KW - endogenous opioid peptides KW - periaqueductal grey matter KW - µ-opioid receptor SP - 1141 EP - 8 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 27 IS - 12 N2 - Previous results with the elevated T-maze (ETM) test indicate that the antipanic action of serotonin (5-HT) in the dorsal periaqueductal grey (dPAG) depends on the activation endogenous opioid peptides. The aim of the present work was to investigate the interaction between opioid- and serotonin-mediated neurotransmission in the modulation of defensive responses in rats submitted to the ETM. The obtained results showed that intra-dPAG administration of morphine significantly increased escape latency, a panicolytic-like effect that was blocked by pre-treatment with intra-dPAG injection of either naloxone or the 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1 piperazinyl] ethyl] -N- 2- pyridinyl-ciclohexanecarboxamide maleate (WAY-100635). In addition, previous administration of naloxone antagonized both the anti-escape and the anti-avoidance (anxiolytic-like) effect of the 5-HT1A agonist (±)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), but did not affect the anti-escape effect of the 5-HT2A agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI). Moreover, the combination of sub-effective doses of locally administered 5-HT and morphine significantly impaired ETM escape performance. Finally, the µ-antagonist D-PHE-CYS-TYR-D-TRP-ORN-THR-PEN (CTOP) blocked the anti-avoidance as well as the anti-escape effect of 8-OHDPAT, and the association of sub-effective doses of the µ-opioid receptor agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin acetate salt (DAMGO) and of 8-OHDPAT had anti-escape and anti-avoidance effects in the ETM. These results suggest a synergic interaction between the 5-HT1A and the µ-opioid receptor at post-synaptic level on neurons of the dPAG that regulate proximal defense, theoretically related to panic attacks. SN - 1461-7285 UR - https://www.unboundmedicine.com/medline/citation/23598399/Cooperative_regulation_of_anxiety_and_panic_related_defensive_behaviors_in_the_rat_periaqueductal_grey_matter_by_5_HT1A_and_μ_receptors_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881113485144?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -