Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB1-cannabinoid receptor in the ventral mesencephalon

Author(s)

da Silva, Juliana Almeida ^{[1, 2]} ; Biagioni, Audrey Francisco ^[1] ; Almada, Rafael Carvalho ^{[1, 2]} ; de Souza Crippa, Jose Alexandre ^[3] ; Cecilio Hallak, Jaime Eduardo ^[3] ; Zuardi, Antonio Waldo ^[3] ; Coimbra, Norberto Cysne ^{[1, 2, 4]}

Affiliation

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

^[2] Behav Neurosci Inst INeC, BR-14050220 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, FMRP, Ribeirao Preto Sch Med, Dept Neurosci & Behav Sci, Div Psychiat, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, FMRP, Ribeirao Preto Sch Med, Neurobiol Emot Res Ctr NAP NuPNE, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 758, p. 153-163, JUL 5 2015.
• Web of Science Citations: 12

Abstract

Many studies suggest that the substantia nigra, pars reticulata (SNpr), a tegmental mesencephalic structure rich in gamma-aminobutyric acid (GABA)- and cannabinoicl receptor-containing neurons, is involved in the complex control of defensive responses through the neostriatum-nigral disinhibitory and nigrotectal inhibitory GABAergic pathways during imminently dangerous situations. The aim of the present work was to investigate the role played by CB1-cannabinoid receptor of GABAergic pathways terminal boutons in the SNpr or of SNpr-endocannabinoid receptor-containing interneurons on the effect of intranigral microinjections of cannabidiol in the activity of nigro-tectal inhibitory pathways. GABA(A) receptor blockade in the deep layers of the superior colliculus (dISC) elicited vigorous defensive behaviour. This explosive escape behaviour was followed by significant antinociception. Cannabidiol microinjection into the SNpr had a clear anti-aversive effect, decreasing the duration of defensive alertness, the frequency and duration of defensive immobility, and the frequency and duration of explosive escape behaviour, expressed by running and jumps, elicited by transitory GABAergic dysfunction in d1SC. However, the innate fear induced-antinociception was not significantly changed. The blockade of CB1 endocannabinoid receptor in the SNpr decreased the anti-aversive effect of canabidiol based on the frequency and duration of defensive immobility, the frequency of escape expressed by running, and both the frequency and duration of escape expressed by jumps. These findings suggest a CB1 mediated endocannabinoid signalling in cannabidiol modulation of panic-like defensive behaviour, but not of innate fear-induced antinociception evoked by GABA(A) receptor blockade with bicuculline microinjection into the superior colliculus, with a putative activity in nigro-collicular GABAergic pathways. (C) 2015 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: 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: 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: 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: 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: 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