title: Serotonin in the dorsal periaqueductal gray inhibits panic-like defensive behaviors in rats exposed to acute hypoxia.
abstract: It has been proposed that spontaneous panic attacks are the outcome of the misfiring of an evolved suffocation alarm system. Evidence gathered in the last years is suggestive that the dorsal periaqueductal gray (dPAG) in the midbrain harbors a hypoxia-sensitive suffocation alarm system. We here investigated whether facilitation of 5-HT-mediated neurotransmission within the dPAG changes panic-like defensive reactions expressed by male Wistar rats submitted to a hypoxia challenge (7% O2), as observed in other animal models of panic. Intra-dPAG injection of 5-HT (20 nmol), (±)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) (8 nmol), a 5-HT1A receptor agonist, or (±)-2,5-dimethoxy-4-iodo amphetamine hydrochloride (DOI) (16 nmol), a preferential 5-HT2A agonist, reduced the number of upward jumps directed to the border of the experimental chamber during hypoxia, interpreted as escape attempts, without affecting the rats' locomotion. These effects were similar to those caused by chronic, but not acute, intraperitoneal administration of the antidepressant fluoxetine (5-15 mg/kg), or acute systemic administration of the benzodiazepine receptor agonist alprazolam (1-4 mg/kg), both drugs clinically used in the treatment of panic disorder. Our findings strengthen the view that the dPAG is a key encephalic area involved in the defensive behaviors triggered by activation of the suffocation alarm system. They also support the use of hypoxia-evoked escape as a model of respiratory-type panic attacks.
authors: Department of Pharmacology, School of Medicine of Ribeirao Preto, University of São Paulo, Avenue Bandeirantes, 3900, Ribeirão Preto CEP: 14049-900, Brazil.
authors: A
authors: A
authors: Spiacci
authors: Department of Pharmacology, School of Medicine of Ribeirao Preto, University of São Paulo, Avenue Bandeirantes, 3900, Ribeirão Preto CEP: 14049-900, Brazil.
authors: T de Oliveira
authors: Tde O
authors: Sergio
authors: Department of Physiology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors: G S F
authors: GS
authors: da Silva
authors: Department of Physiology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors: M L
authors: ML
authors: Glass
authors: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Brazil.
authors: L C
authors: LC
authors: Schenberg
authors: Department of Physiology, School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors: N
authors: N
authors: Garcia-Cairasco
authors: Department of Pharmacology, School of Medicine of Ribeirao Preto, University of São Paulo, Avenue Bandeirantes, 3900, Ribeirão Preto CEP: 14049-900, Brazil. Electronic address: zangross@fmrp.usp.br.
authors: H
authors: H
authors: Zangrossi
mesh_terms: D000525:Alprazolam / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003674:Defense Mechanisms; D004305:Dose-Response Relationship, Drug; D018757:GABA Modulators / Q000494:pharmacology; D000860:Hypoxia / Q000150:complications* / Q000473:pathology*; D008297:Male; D008845:Microinjections; D010200:Panic / Q000502:physiology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology
chemical_list: D018757:GABA Modulators; D018490:Serotonin Agents; D012701:Serotonin; D000525:Alprazolam
keywords: hypoxia; periaqueductal gray; respiratory panic; serotonin