title: Interaction between μ-opioid and 5-HT1A receptors in the regulation of panic-related defensive responses in the rat dorsal periaqueductal grey.
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.
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil.
authors.forename: Marcel P
authors.initials: MP
authors.lastname: Rangel
authors.affiliation: 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.
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Roncon
authors.affiliation: INeC - Institute of Behavioral Neuroscience, Ribeirão Preto, Brazil NAP-NuPNE - Neurobiology of Emotion Research Centre, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Frederico G
authors.initials: FG
authors.lastname: Graeff
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil INeC - Institute of Behavioral Neuroscience, Ribeirão Preto, Brazil elisabethaudi8@gmail.com.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Audi
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008845:Microinjections; D010200:Panic / Q000187:drug effects / Q000502:physiology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D044282:Receptor, Serotonin, 5-HT1A; D013004:Somatostatin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin
keywords: 5-HT1A receptor; Panic; dorsal periaqueductal grey; μ-opioid receptor