Endocannabinoid neuromodulation in the neostriatum decreases the GABAergic striato-nigral disinhibitory function and increases the nigro-collicular inhibitory pathway activity

Author(s)

da Silva, Juliana Almeida ^{[1, 2]} ; Almada, Rafael Carvalho ^{[1, 2, 3]} ; de Paiva, Yara Bezerra ^{[1, 2]} ; Coimbra, Norberto Cysne ^{[1, 2, 4]}

Affiliation

^[1] Behav Neurosci Inst INeC, Av Cafe 2450, BR-14050220 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Farmacol, Lab Neuroanat & Neuropsicobiol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Sao Paulo State Univ, UNESP, Sch Sci Humanities & Languages, Dept Biol Sci, BR-19806900 Assis, SP - Brazil

^[4] Univ Sao Paulo, FMRP, Ribeirao Preto Med Sch, NAP Neurobiol Emot Res Ctr NuPNE, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF NEURAL TRANSMISSION; v. 127, n. 8 JUN 2020.
• Web of Science Citations: 0

Abstract

We previously reported the involvement of neostriato-nigral projections in the organisation of innate fear and panic attack-like responses organised by dorsal midbrain neurons, such as the periaqueductal grey matter and the deep layers of the superior colliculus (dlSC). In addition, several lines of evidence have demonstrated that cannabinoid receptor type 1 is found in the neostriatum (caudate nucleus and putamen; CPu). In the present study, we investigated the role of endocannabinoid neuromodulation in CPu in the expression of unconditioned fear-related behavioural responses elicited by microinjections of the gamma-aminobutyric acid (GABA)(A)receptor selective antagonist bicuculline (BIC) in the dlSC. Wistar rats received injection of vehicle or anandamide (AEA) at 0.5, 5, 50, 100 pmol in CPu, followed by injections of BIC in a dose of 40 ng in the dlSC. The treatment of the CPu with AEA in a dose of 5 and 50 pmol attenuated the unconditioned fear-related behaviour, such as defensive alertness, defensive immobility and escape, induced by GABA(A)receptor blockade in dlSC. These findings suggest that endogenous cannabinoids acting on CPu neurons exert an indirect modulatory influence on the activity of superior colliculus neurons, possibly through an inhibitory activity on neostriato-nigral disinhibitory connections that modulate the nigro-collicular inhibitory GABAergic pathways. (AU)

• FAPESP's process: 19/01713-7 - Fear and anxiety: role of orexinergic system in the prefrontal cortex
• Grantee: Rafael Carvalho Almada
• Support type: Scholarships in Brazil - Young Researchers
• 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 type: 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 type: Scholarships in Brazil - Post-Doctorate
• 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 type: 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 type: 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 type: Regular Research Grants
• FAPESP's process: 18/03898-1 - Fear and anxiety: role of the orexinergic system in the medial prefrontal cortex
• Grantee: Rafael Carvalho Almada
• Support type: Research Grants - Young Investigators 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 type: Scholarships in Brazil - Post-Doctorate