The alpha- and beta-noradrenergic receptors blockade in the dorsal raphe nucleus impairs the panic-like response elaborated by medial hypothalamus neurons

Author(s):Show less -

Uribe-Marino, Andres ^{[1, 2]} ; Castiblanco-Urbina, Maria Angelica ^{[1, 3]} ; Falconi-Sobrinho, Luiz Luciano ^{[4, 1, 5]} ; dos Anjos-Garcia, Tayllon ^{[4, 1, 5]} ; de Oliveira, Rithiele Cristina ^{[4, 1, 5]} ; Mendes-Gomes, Joyce ^{[4, 1, 5]} ; Soares, Jr., Raimundo da Silva ^[1] ; Matthiesen, Melina ^[1] ; Almada, Rafael Carvalho ^{[4, 1, 5]} ; de Oliveira, Ricardo ^{[4, 1, 6]} ; Coimbra, Norberto Cysne ^{[4, 1, 5]}

Affiliation

^[1] Univ Sao Paulo, FMRP, Ribeirao Preto Med Sch, Lab Neuroanat & Neuropsychobiol, Dept Pharmacol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Max Planck Inst Psychiat, Dept Stress Neurobiol & Neurogenet, Kraepelinstr 2-10, D-80804 Munich - Germany

^[3] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Dev Genet, Ingolstaedter Landstr 1, Neuherberg - Germany

^[4] Behav Neurosci Inst INeC, Ave Cafe 2450, BR-14220030 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, FMRP, Ribeirao Preto Med Sch, Neurobiol Emot Res Ctr NuPNE, NAP, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[6] Univ Fed Mato Grosso, Med Sch UFMT, Hlth Sci Inst, Av Alexandre Ferronato 1200, Reserva 35, BR-78550000 Sinop, Mato Grosso - Brazil

• Document type: Journal article
• Source: Brain Research; v. 1725, DEC 15 2019.
• Web of Science Citations: 0

Abstract

Dorsal raphe nucleus (DRN) neurons are reciprocally connected to the locus coeruleus (LC) and send neural pathways to the medial hypothalamus (MH). The aim of this work was to investigate whether the blockade of alpha(1)-, alpha(2)- or beta-noradrenergic receptors in the DRN or the inactivation of noradrenergic neurons in the LC modify defensive behaviours organised by MH neurons. For this purpose, Wistar male rats received microinjections of WB4101, RX821002, propranolol (alpha(1)-, alpha(2)- and beta-noradrenergic receptor antagonists, respectively) or physiological saline in the DRN, followed 10 min later by MH GABA(A) receptor blockade. Other groups of animals received DSP-4 (a noradrenergic neurotoxin), physiological saline or only a needle insertion (sham group) into the LC, and 5 days later, bicuculline or physiological saline was administered in the MH. In all these cases, after MH treatment, the frequency and duration of defensive responses were recorded over 15 min. An anterograde neural tract tracer was also deposited in the DRN. DRN neurons send pathways to lateral and dorsomedial hypothalamus. Blockade of alpha(1)- and beta-noradrenergic receptors in the DRN decreased escape reactions elicited by bicuculline microinjections in the MH. In addition, a significant increase in anxiety-like behaviours was observed after the blockade of alpha(2)-noradrenergic receptors in the DRN. LC pretreatment with DSP-4 decreased both anxiety- and panic attack-like behaviours evoked by GABA(A) receptor blockade in the MH. In summary, the present findings suggest that the norepinephrine-mediated system modulates defensive reactions organised by MH neurons at least in part via noradrenergic receptors recruitment on DRN neurons. (AU)

• FAPESP's process: 09/54014-7 - Acquisition of a biophotonic imaging system and a multiphoton microscopy system for in vivo imaging
• Grantee: Enilza Maria Espreafico
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 07/01174-1 - Study of the Involvement of opioid-, serotonergic- and noradrenergic-mechanisms of the pain endogenous inhibitory system in antinociceptive processes induced by oriented escape reactions evoked by chemical stimulation of the merdial hypothalamus
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants