title: Cooperative regulation of anxiety and panic-related defensive behaviors in the rat periaqueductal grey matter by 5-HT1A and μ-receptors.
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.affiliation: 1Department of Pharmacology and Therapeutics, State University of Maringá, Brazil.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Roncon
authors.forename: Carla
authors.initials: C
authors.lastname: Biesdorf
authors.forename: Norberto C
authors.initials: NC
authors.lastname: Coimbra
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Audi
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
authors.forename: Frederico G
authors.initials: FG
authors.lastname: Graeff
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D010200:Panic / Q000502:physiology*; D016584:Panic Disorder / Q000378:metabolism; D010487:Periaqueductal Gray / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000008:administration & dosage / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D017450:Receptors, Opioid, mu; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D009270:Naloxone; D009020:Morphine
keywords: 5-HT1A receptor; Serotonin; elevated T-maze; endogenous opioid peptides; periaqueductal grey matter; µ-opioid receptor