Dorsal raphe nucleus 5-Hydroxytryptamine 2A receptors are critical for the organisation of panic attack-like defensive behaviour and unconditioned fear-induced antinociception elicited by the chemical stimulation of superior colliculus neurons

Author(s)

Soares, Jr., Raimundo da Silva ^{[1, 2, 3]} ; Falconi-Sobrinho, Luiz Luciano ^{[1, 2, 3]} ; Almada, Rafael Carvalho ^{[1, 2]} ; Coimbra, Norberto Cysne ^{[1, 2, 3]}

Affiliation

^[1] Behav Neurosci Inst INeC, Ave Cafe 2450, BR-14220030 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo FMRP USP, Ribeirao Preto Med Sch, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, Av Bandeirantes 3900, BR-14049900 Sao Paulo - Brazil

^[3] Univ Sao Paulo FMRP USP, Ribeirao Preto Sch Med, NAP USP Neurobiol Emot Res Ctr NuPNE, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: European Neuropsychopharmacology; v. 29, n. 7, p. 858-870, JUL 2019.
• Web of Science Citations: 1

Abstract

Microinjections of N-methyl-D-aspartic acid (NMDA) in the midbrain tectum structures produce panic attack-like defensive behaviours, followed by an antinociceptive response. It has been suggested that fear-related defensive responses organised by brainstem neurons can be modulated by 5-hydroxytryptamine (5-HT). However, there is a shortage of studies showing the role of dorsal raphe nucleus (DRN) 5-HT2A receptors in the modulation of panic-like behaviour and fear-induced antinociception organised by the superior colliculus (SC). The purpose of this study was to investigate the participation of DRN 5-HT2A receptors in the modulation of panic attack-like behaviour and antinociception evoked by intra-SC injections of NMDA. In experiment I, the animals received microinjections of physiological saline or NMDA (6, 9 and 12 nmol) in the deep layers of the SC (dlSC). In experiment II, the most effective dose of NMDA (12 nmol) or vehicle was preceded by microinjections of vehicle or the 5-HT2A receptor selective antagonist R-96544 at different concentrations (0.5, 5 and 10 nM) in the DRN. Both proaversive and antinociceptive effects elicited by intra-dlSC injections of NMDA were attenuated by DRN pretreatment with R-96544. In addition, a morphological analysis showed that 5-HT2A receptors are present in GABAergic interneurons in the DRN. Taken together, these findings suggest that DRN 5-HT2A receptors are critical for the modulation of both panic attack-like defensive behaviour organised by SC neurons and unconditioned fear-induced antinociception. A possible interaction between serotonergic inputs, GABAergic interneurons and serotonergic outputs from the DRN was also considered. (C) 2019 Elsevier B.V. and ECNP. All rights reserved. (AU)

• 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
• FAPESP's process: 12/03798-0 - Involvement of opioid and endocanabinoid receptors of the substantia nigra on the activity of Nigro-Tectal GABAergic pathways during defensive behaviour elicited by rodents confronted with venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants