title: Dorsomedial hypothalamus serotonin 1A receptors mediate a panic-related response in the elevated T-maze.
abstract: The dorsomedial hypothalamus (DMH) has long been associated with the regulation of escape, a panic-related defensive response. Previous evidence has shown that the activation of serotonin (5-HT) 1A and 2A receptors impairs escape behavior induced by the electrical stimulation of the same region. In this study we further explore the relationship of the DMH with defense by investigating the effects of 5-HT1A activation on escape behavior generated in male Wistar rats by an ethologically based aversive stimuli, exposure to one of the open arms of the elevated T-maze (ETM). Aside from escape, the ETM also allows the measurement of inhibitory avoidance, a defensive response associated with generalized anxiety disorder. To evaluate locomotor activity, after ETM measurements animals were submitted to an open field. Results showed that intra-DMH administration of the 5-HT1A receptor agonist 8-OH-DPAT inhibited escape expression. Local administration of the 5-HT1A antagonist WAY-100635 by its own was ineffective, but blocked the panicolytic-like effect of 8-OH-DPAT. Chronic (21 days) systemic treatment with imipramine potentiated the anti-escape effect of 8-OH-DPAT. No significant effects of treatment with 8-OH-DPAT or imipramine on avoidance latencies or the number of lines crossed in the open field were found. These results indicate that 5-HT1A receptors within the DMH may play a phasic inhibitory role on ETM escape expression. As previously proposed, facilitation of 5-HT1A-mediated neurotransmission in the DMH may be involved in the mechanism of action of anti-panic compounds.
authors.affiliation: Departamento de Psiquiatria e Psicologia Médica, Universidade Federal de São Paulo, 04038-020 São Paulo, Brazil.
authors.forename: Juliana O G
authors.initials: JO
authors.lastname: Nascimento
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001 Santos, Brazil.
authors.forename: Letícia Sumiko
authors.initials: LS
authors.lastname: Kikuchi
authors.affiliation: Departamento de Ciências da Saúde, Universidade Federal do Espírito Santo, 29932-540 São Mateus, Brazil.
authors.forename: Valquíria Camin
authors.initials: VC
authors.lastname: de Bortoli
authors.affiliation: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirão Preto, Brazil.
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001 Santos, Brazil. Electronic address: mviana@unifesp.br.
authors.forename: Milena B
authors.initials: MB
authors.lastname: Viana
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004195:Disease Models, Animal; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D004924:Escape Reaction / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D016584:Panic Disorder / Q000139:chemically induced / Q000175:diagnosis* / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000633:toxicity
chemical_list: D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin
keywords: Dorsomedial hypothalamus; Elevated T-maze; Escape; Panic; Serotonin 1A receptors