Panicolytic-like effects caused by substantia nigra pars reticulata pretreatment with low doses of endomorphin-1 and high doses of CTOP or the NOP receptors antagonist JTC-801 in male Rattus norvegicus

Author(s)

da Silva, Juliana Almeida ; Biagioni, Audrey Franceschi ; Almada, Rafael Carvalho ; de Freitas, Renato Leonardo ; Coimbra, Norberto Cysne

• Document type: Journal article
• Source: Psychopharmacology; v. 234, n. 20, p. 3009-3025, OCT 2017.
• Web of Science Citations: 7

Abstract

Gamma-aminobutyric acid (GABA)ergic neurons of the substantia nigra pars reticulata (SNpr) are connected to the deep layers of the superior colliculus (dlSC). The dlSC, in turn, connect with the SNpr through opioid projections. Nociceptin/orphanin FQ peptide (N/OFQ) is a natural ligand of a Gi protein-coupled nociceptin receptor (ORL1; NOP) that is also found in the SNpr. Our hypothesis is that tectonigral opioid pathways and intranigral orphanin-mediated mechanisms modulate GABAergic nigrotectal connections. Therefore, the aim of this work was to study the role of opioid and NOP receptors in the SNpr during the modulation of defence reactions organised by the dlSC. The SNpr was pretreated with either opioid or NOP receptor agonists and antagonists, followed by dlSC treatment with bicuculline. Blockade of GABA(A) receptors in the dlSC elicited fear-related defensive behaviour. Pretreatment of the SNpr with naloxone benzoylhydrazone (NalBzoH), a mu-, delta-, and kappa(1)-opioid receptor antagonist as well as a NOP receptor antagonist, decreased the aversive effect of bicuculline treatment on the dlSC. Either mu-opioid receptor activation or blockade by SNpr microinjection of endomorphin-1 (EM-1) and CTOP promoted pro-aversive and anti-aversive actions, respectively, that modulated the defensive responses elicited by bicuculline injection into the dlSC. Pretreatment of the SNpr with the selective NOP receptor antagonist JTC801 decreased the aversive effect of bicuculline, and microinjections of the selective NOP receptor agonist NNC 63-0532 promoted the opposite effect. These results demonstrate that opioid pathways and orphanin-mediated mechanisms have a critical role in modulating the activity of nigrotectal GABAergic pathways during the organisation of defensive behaviours. (AU)

• FAPESP's process: 14/11869-0 - Multi-use equipment approved in grant 2013/12916-0: deep brain stimulation (DBS) (Thomas mini matrix system - Thomas recording GmbH® - Winchester Strasse - Giessen - Germany)
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Multi-user Equipment Program
• 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: 14/10742-7 - Paresthesia as a new approach of study for panic disorder: basic and clinical research
• Grantee: Audrey Franceschi Biagioni
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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
• 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: 10/15140-4 - Neuropharmacological study of the involvement of dorsal rafe nucleus and serotoninergic systems in the antinociceptive process induced by oriented escape reaction evoked by GABAergic disinhibition of the dorsomedial hypothalamus
• Grantee: Audrey Franceschi Biagioni
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/12916-0 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Research Grants - Young Investigators Grants
• 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
• 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: 15/10313-1 - Study of nigro-tectal GABAergic pathways activity during the elaboration of defensive behaviour: role of endocannabinoid mediated neuromodulation in the caudatum putamen of the GABAergic disinhibitory neostriatum-nigral inhibitory nigro-collicular pathways
• Grantee: Juliana Almeida da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/22681-7 - Involvement of Opioid and Endocanabinoid Receptors of the Substantia Nigra, Pars Reticulata, in the Modulation of the Activity of Nigro-Tectal GABAergic Pathways during the Organization of Defensive Behaviour of Mice Confronted with Venomous Snakes
• Grantee: Rafael Carvalho Almada
• Support Opportunities: Scholarships in Brazil - Post-Doctoral