Decrease in NMDA receptor-signalling activity in the anterior cingulate cortex diminishes defensive behaviour and unconditioned fear-induced antinociception elicited by GABAergic tonic inhibition impairment in the posterior hypothalamus

Author(s)

Falconi-Sobrinho, Luiz Luciano ^[1] ; dos Anjos-Garcia, Tayllon ^[1] ; de Oliveira, Ricardo ^{[1, 2, 3]} ; Coimbra, Norberto Cysne ^{[1, 4, 2]}

Affiliation

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

^[2] Behav Neurosci Inst INeC, Ave Cafe 2450, BR-14220030 Sao Paulo - Brazil

^[3] Univ Fed Mato Grosso, Med Sch UFMT, Setor Ind, Ave Alexandre Ferronato 1200, Reserva 35, BR-78550000 Sinop, Mato Grosso - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, NAP USP Neurobiol Emot NuPNE Res Ctr, Ave Bandeirantes 3900, BR-14049900 Sao Paulo - Brazil

• Document type: Journal article
• Source: European Neuropsychopharmacology; v. 27, n. 11, p. 1120-1131, NOV 2017.
• Web of Science Citations: 8

Abstract

Acute gamma-aminobutyric acid (GABA) disinhibition in the posterior hypothalamus (PH) elicits defensive reactions that are considered anxiety- and panic attack-like behaviour, and these defensive reactions are followed by antinociception. Evidence indicates that the PH connects with the medial prefrontal cortex, particularly the anterior cingulate cortex (ACC), which seems to regulate these unconditioned fear-induced defensive responses. However, few studies have shown the participation of cortical regions in the control of behavioural and antinociceptive responses organised by diencephalic structures. It has been suggested that the glutamatergic system can mediate this cortical influence, as excitatory imbalance is believed to play a role in both defensive mechanisms. Thus, the aim of the present study was to investigate the involvement of ACC glutamatergic connections via blockade of local N-methyl-D-aspartate (NMDA) receptors to elaborate panic-like defensive behaviours and unconditioned fear-induced antinociception organised by PH neurons. Wistar rats were treated with micro injections of 0.9% NaCl or LY235959 (a selective NMDA receptor antagonist) in the ACC at different concentrations (2, 4 and 8 nmol/0.2 mu L), followed by GABAA receptor blockade in the PH. Defensive reactions were analysed for 20 min, and the nociceptive threshold was then measured at 10-min intervals for 60 min. Pretreatment of the ACC with LY235959 reduced both panic-like defensive behaviour and fear-induced antinociception evoked by PH GABAergic disinhibition. Our findings suggest that ACC NMDA receptor-signalled glutamatergic inputs play a relevant role in the organisation of anxiety- and panic attack-like behaviours and in fear induced antinociception. (C) 2017 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: 17/11855-8 - Study of corpus striatum and ventral mesencephalon endocanabinoid influence on neostriato-nigro-tectal GABAergic pathways during panic reactions of rodents threatened by venomous snakes
• 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