The modulation of striatonigral and nigrotectal pathways by CB1 signalling in the substantia nigra pars reticulata regulates panic elicited in mice by urutu-cruzeiro lancehead pit vipers

Author(s)

Almada, Rafael Carvalho ^{[1, 2, 3, 4]} ; dos Anjos-Garcia, Tayllon ^{[2, 4]} ; da Silva, Juliana Almeida ^{[1, 2]} ; Pigatto, Glauce Regina ^[2] ; Wotjak, Carsten T. ^[3] ; Coimbra, Norberto Cysne ^{[1, 2, 4, 5]}

Affiliation

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

^[2] Univ Sao Paulo FMRP USP, Sch Med Ribeirao Preto, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Max Planck Inst Psychiat, Dept Stress Neurobiol & Neurogenet, Lab Neuronal Plast, Kraepelinstr 2-10, D-80804 Munich - Germany

^[4] Univ Sao Paulo, Ophidiarium LNN FMRP USP INeC, Ribeirao Preto Med Sch, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, NAP USP Neurobiol Emot Res Ctr NuPNE, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Behavioural Brain Research; v. 401, MAR 5 2021.
• Web of Science Citations: 0

Abstract

Cannabinoid receptor type 1 (CB1R) is widely distributed in the substantia nigra pars reticulata (SNpr). However, the role of CB1R at the SNpr level in threatening situations is poorly understood. We investigated the role of CB1R in the SNpr on the expression of fear responses in mice confronted with urutu-cruzeiro pit vipers. First, a bidirectional neumtracer was injected into the SNpr; then, immunostaining of the vesicular GABA transporter was conducted at the levels of the striatum (CPu) and deep layers of the superior colliculus (d1SC). In addition, CB1R immunostaining and GABA labelling were performed in the SNpr. Using a prey-versus-snake paradigm, mice were pretreated with the CB1R antagonist AM251 (100 pmol) and treated with the endocannabinoid anandamide (AEA, 5 pmol) in the SNpr, followed by bicuculline (40 ng) in the dlSC, and were then confronted with a snake. Bidirectional neural tract tracers associated with immunofluorescence showed the GABAergic striatonigral disinhibitory and nigrotectal inhibitory pathways. Furthermore, we showed that CB1R labelling was restricted to axonal fibres surrounding SNpr GABAergic cells. We also demonstrated a decrease in the defensive behaviours of mice treated with AEA in the SNpr, but this effect was blocked by pre-treatment with AM251 in this structure. Taken together, our results show that the panicolytic consequences of the AEA enhancement in the SNpr are signalled by CB1R, suggesting that CB1R localised in axon terminals of CPu GABAergic neurons in the SNpr modulates the activity of the nigrotectal GABAergic pathway during the expression of defensive behaviours in threatening situations. (AU)

• 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: 12/03798-0 - 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: 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