mu- and kappa-Opioid receptor activation in the dorsal periaqueductal grey matter differentially modulates panic-like behaviours induced by electrical and chemical stimulation of the inferior colliculus

Autor(es)

Twardowschy, Andre ^[1] ; Coimbra, Norberto Cysne ^{[2, 1, 3]}

Afiliação do(s) autor(es)

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

^[2] Inst Neurosci & Behav INeC, BR-14050220 Sao Paulo - Brazil

^[3] FMRP USP, NAP USP Neurobiol Emot NuPNE Res Ctr, BR-14049900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Brain Research; v. 1597, p. 168-179, FEB 9 2015.
• Citações Web of Science: 13

Resumo

It has been shown that electrical stimulation of the mesencephalic tectum (MT) provokes defensive responses in both humans and rodents. During an emotional aversive state, some convergent studies have also demonstrated the existence of a complex interaction between endogenous opioid peptide- and gamma-aminobutyric acid (GABA)-containing connections during fear-induced responses. It has been proposed that opioid neurons exert an influence on GABAergic intemeurons, which, in turn, exert inhibitory tonic control on the mesencephalic excitatory pathways. Thus, opioid peptides can disinhibit neurons that are tonically inhibited by GABA, therefore, modulating the expression of defensive behavioural reactions. In the present work, we used both electric stimulation and microinjections of the GABA(A) receptor antagonist bicuculline in the inferior colliculus (IC) of Wistar rats in combination with microinjections of mu- and kappa-opioid receptor selective agonists into the dorsal columns of periaqueductal grey matter (dPAG) to evaluate the effects on panic-like behaviours elicited by IC electrical and chemical stimulation. The present results showed that neurochemical lesions of the dPAG caused a significant impairment in the organisation of defensive responses by IC neurons, reducing the duration {[}t((14))=3.0; p<0.01] of defensive immobility and the duration {[}t((14))= 2.8; p <0.05] and frequency {[}t((14))=2.5; p <0.05] of escape. Paradoxically, treating the dPAG with the R-opioid receptor agonist metenkephalin caused a significant reduction of panic-like behaviours induced by both electrical and chemical stimulation of the IC, increasing the escape behaviour threshold {[}F-(2,F-23) =13.5; p <0.001] and decreasing the frequency {[}F-(3,F-36)=11.7; p <0.001] and duration {[}F-(3,F-36)=11.6; p <0.001] of escape and the duration of defensive immobility {[}F-(3,F-36)=16.1; p <0.05]. In contrast, treating the dPAG with the kappa-opioid receptor agonist salvinorin-A increased the frequency {[}F-(3,F-36)=12.4; p <0.01] and duration {[}F-(3,F-34)=16.1; p <0.01] of defensive immobility induced by GABA(A) receptor blockade in the IC. The present results suggest the existence of a complex neuronal network in the MT in which endogenous opioid peptides and GABAergic pathways interact in the control of fear-related behavioural responses. (C) 2014 Elsevier B.V. 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: 08/00531-8 - Estudo da Interação entre Circuitos Opióides e GABAérgicos no Mesencéfalo Dorsal e de seu Papel na Modulação do Comportamento de Defesa Organizado no Colículo Inferior e na Substância Cinzenta Periaquedutal Dorsal
• Beneficiário: Andre Twardowschy
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/54014-7 - EMU: aquisição dos equipamentos IVIS Spectrum e microscópio de excitação por dois fótons para imagem in vivo
• Beneficiário: Enilza Maria Espreafico
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 02/01497-1 - Estudo do envolvimento do núcleo magno da rafe, do núcleo gigantocelular e núcleo pré-tectal anterior, e de receptores opiódes, kappa e delta serotoninérgicos 5HT2/1C, e noradrenérgicos alfa, beta, na analgesia pós-cital: um estudo neuroanatômico e neuropsicofisiológico em um modelo experimental de epilepsia
• Beneficiário: Daoud Hibrahim Elias Filho
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico