5-HT1A receptors of the rat dorsal raphe lateral wings and dorsomedial subnuclei differentially control anxiety- and panic-related defensive responses

Autor(es)

Spiacci, Jr., Ailton ^[1] ; Henschel Pobbe, Roger Luis ^[1] ; Matthiesen, Melina ^[1] ; Zangrossi, Jr., Helio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuropharmacology; v. 107, p. 471-479, AUG 2016.
• Citações Web of Science: 8

Resumo

The dorsal raphe nucleus (DR), the main source of 5-HT projections to brain areas involved in anxiety regulation, is composed by 5 subnuclei that differ morphologically, functionally and neurochemically. Based on immunohistochemical evidence, it has been proposed that whereas 5-HT cells of the dorsomedial (dmDR) and caudal subnuclei are implicated in the pathophysiology of generalized anxiety disorder (GAD), neurons of the lateral wings (1wDR) are associated with panic disorder (PD). We here tested this hypothesis from a behavioral perspective by investigating the consequences of the non-selective stimulation of neurons within the dmDR and 1wDR, or the pharmacological manipulation of 5-HT1A receptors located in these nuclei, of male Wistar rats exposed to the elevated T-maze. This test allows the measurement of both a GAD- (i.e. inhibitory avoidance) and a PD- (i.e. escape) related response in the same animal. Intra-dmDR injection of either the excitatory amino acid kainic acid or the 5-HT1A receptor antagonist WAY-100635 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, and inhibited escape expression, a panicolytic-like effect. Microinjection of the 5-HT1A receptor agonist 8-OH-DPAT caused the opposite effect. Administration of the same drugs into the 1wDR only altered escape performance. Whereas kainic acid and 8-OH-DPAT facilitated its expression, WAY-100635 inhibited it. At higher doses, kainic acid administration evoked vigorous escape reactions as measured in an open-field. These findings implicate 5-HT neurons of the dmDR in the regulation of both GAD- and PD-related defensive behaviors. They also support a primary role of the 1wDR in the mediation of PD associated responses. (c) 2015 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 12/17626-7 - Mecanismos celulares e moleculares envolvidos no papel de neurotransmissores atípicos em transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/03065-6 - Efeitos da manipulação farmacológica das sub-regiões do núcleo dorsal da rafe na modulação de comportamentos associados aos transtornos de ansiedade generalizada e do pânico
• Beneficiário: Roger Luís Henschel Pobbe
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado