Chemical neuroanatomical and psychopharmacological evidence that kappa receptor-mediated endogenous opioid peptide neurotransmission in the dorsal and ventral mesencephalon modulates panic-like behaviour

Author(s)

da Silva, Juliana Almeida ^{[1, 2]} ; de Freitas, Renato Leonardo ^{[1, 2]} ; Dutra Eichenberger, Gustavo Cavalcanti ^[1] ; Padovan, Claudia Maria ^{[2, 3, 4]} ; Coimbra, Norberto Cysne ^{[1, 2, 4]}

Affiliation

^[1] Univ Sao Paulo, Dept Farmacol, Lab Neuroanat & Neuropsicobiol, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Inst Neurociencias & Comportamento INeC, BR-14049901 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Lab Neurobiol Estresse & Depressao, Dept Psicol, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14049901 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, NAP USP Neurobiol Emocoes NuPNE, Dept Farmacol, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 698, n. 1-3, p. 235-245, JAN 5 2013.
• Web of Science Citations: 13

Abstract

The chemical neuroanatomy and the effects of central administration of opioid antagonists on the innate fear-induced responses elicited by electrical (at escape behaviour threshold) stimulation of the midbrain tectum were determined. The aim of the present work was to investigate the interaction between the tecto-nigral endogenous opioid peptide-mediated disinhibitory pathways and nigro-tectal inhibitory links in the control of panic-like behaviour and their organisation in the continuum comprised by the deep layers of the superior colliculus (dISC) and the dorsolateral columns of the periaqueductal grey matter (dlPAG ). Beta-endorphin-labelled neurons and fibres were found in the dorsal midbrain and also in the substantia nigra. Opioid varicose fibres and terminal buttons were widely distributed in PAG columns and in all substantia nigra subdivisions. Microinjections of naltrexone (a non-selective opioid receptor antagonist; 5.0 mu g/0.2 mu l) or nor-binaltorphimine (a selective kappa-opioid receptor antagonist; 5.0 mu g/0.2 mu l) in the dlSC/dlPAG continuum, in independent groups of animals, induced significant increases in the escape thresholds for midbrain tectum electrical stimulation. The microinjection of naltrexone or nor-binaltorphimine into the SNpr also increased the escape behaviour threshold for electrical stimulation of dlSC/dlPAG . These morphological and neuropharmacological findings support previous evidence from our team for the role played by the interaction between opioidergic and GABAergic mechanisms in the modulation of innate fear-induced responses. The present data offer a neuroanatomical basis for both intratectal axo-axonic/pre-synaptic and tecto-nigral axo-somatic opioid inhibition of GABAergic nigro-tectal neurons that modulate the dorsal midbrain neurons related to the organisation of fear-related emotional responses. (c) 2012 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 09/02458-9 - Neuropharmacological study of the interaction between cannabinoid and opioid circuits of the substantia nigra, pars reticulata, on the activity of the nigrotectal GABAergic pathways, and of its role in the modulation of the innate fear-induced analgesia
• Grantee: Juliana Almeida da Silva
• Support Opportunities: Scholarships in Brazil - Master
• 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: 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: 09/17258-5 - Study of the involvement of nitrergic system and of glutamatergic and cannabinoid-mediated neurotransmission from the medial prefrontal cortex in the analgesia induced by elaborated escape reactions evoked by GABAergic blockade in the medial hypothalamus
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral