title: Effects of chemical stimulation of the lateral wings of the dorsal raphe nucleus on panic-like defensive behaviors and Fos protein expression in rats.
abstract: The lateral wings subnucleus of the dorsal raphe nucleus (lwDR) has been implicated in the modulation of panic-like behaviors, such as escape. Infusion of non- excitotoxic doses of the excitatory amino acid kainic acid into this subnucleus promptly evokes a vigorous escape response. In addition, rats exposed to panic-inducing situations show an increase in Fos protein expression in neurons within the lwDR. In the present study, we first investigated whether key structures associated with the mediation of escape behavior are recruited after chemical stimulation of the lwDR with kainic acid. We next investigated whether the infusion of the GABAAreceptor antagonist bicuculline into the lwDR also evoked escape responses measured both in a circular arena and in the rat elevated T-maze. The effects of bicuculline in the circular arena were compared to those caused by the infusion of this antagonist into the ventrolateral periaqueductal gray (vlPAG), an area in close vicinity to the lwDR. The results showed that kainic acid infusion into the lwDR increased Fos protein immunostaining in brain structures deeply involved in panic-like defensive behaviors, such as the periaqueductal gray and hypothalamus, but not the amygdala. As observed with kainic acid, bicuculline evoked a pronounced escape response in the circular arena when microinjected in the lwDR, but not in the vlPAG. The escape-promoting effect of bicuculline in the lwDR was also evidenced in the elevated T-maze. These findings strength the view that dysfunction in mechanisms controlling escape in the lwDR is critically implicated in the pathophysiology of panic disorder.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, 14049-900, Brazil.
authors.forename: Melina
authors.initials: M
authors.lastname: Matthiesen
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, 14049-900, Brazil.
authors.forename: Ailton
authors.initials: A
authors.lastname: Spiacci
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, 14049-900, Brazil. Electronic address: zangross@fmrp.usp.br.
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology*; D065847:Dorsal Raphe Nucleus / Q000187:drug effects*; D004924:Escape Reaction / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010200:Panic / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
chemical_list: D018690:Excitatory Amino Acid Agonists; D058787:GABA-A Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos; D007608:Kainic Acid; D001640:Bicuculline
keywords: Dorsal raphe lateral wings; Hypothalamus; Kainic acid and bicuculline; Panic; Periaqueductal gray