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

Autor(es)

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

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: European Neuropsychopharmacology; v. 27, n. 11, p. 1120-1131, NOV 2017.
• Citações Web of Science: 8

Resumo

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)

• Processo FAPESP: 07/01174-1 - Estudo do envolvimento do sistema opióide, serotoninérgico e noradrenérgico do sistema endógeno de inibição de dor em processos antinociceptivos induzidos por reações de fuga orientada evocada pela estimulação química do hipotálamo medial
• Beneficiário: Norberto Cysne Coimbra
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/11855-8 - Estudo da influência de endocanabinoides do corpo estriado e do mesencéfalo ventral na atividade das projeções GABAérgicas neoestriado-nigro-tectais durante as reações de pânico de roedores ameaçados por serpentes peçonhentas
• Beneficiário: Norberto Cysne Coimbra
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/03798-0 - Envolvimento de receptores opióides e endocanabinóides da substância negra na modulação da atividade da via GABAérgica nigro-tectal durante a organização do comportamento de defesa eliciado por roedores confrontados com serpentes veneníferas
• Beneficiário: Norberto Cysne Coimbra
• Modalidade de apoio: Auxílio à Pesquisa - Regular