Opposing roles of dorsomedial hypothalamic CB1 and TRPV1 receptors in anandamide signaling during the panic-like response elicited in mice by Brazilian rainbow Boidae snakes

  • Tayllon dos Anjos-Garcia
  • Norberto Cysne CoimbraEmail author
Original Investigation



The endocannabinoid system plays an important role in the organization of panic-like defensive behavior. Threatening situations stimulate brain areas, such as the dorsomedial hypothalamus (DMH). However, there is a lack of studies addressing the role of the DMH endocannabinoid system in panic-like responses.


We aimed to verify which mechanisms underlie anandamide-mediated responses in the DMH.


To test the hypothesis that the anandamide produces panicolytic-like effects, we treated mice with intra-DMH microinjections of vehicle or increasing doses of anandamide (0.5, 5, or 50 pmol) and then performed confrontation with the South American snake Epicrates cenchria assisi.


Intra-DMH anandamide treatment yielded a U-shaped dose-response curve with no effect of the lowest (0.5 pmol) or the highest (50 pmol) dose and significant inhibition of panic-like responses at the intermediate (5 pmol) dose. In addition, this panicolytic-like effect was prevented by pretreatment of the DMH with the CB1 receptor antagonist AM251 (100 pmol). However, pretreatment of the DMH with the TRPV1 receptor antagonist 6-iodo-nordihydrocapsaicin (3 nmol) restored the panicolytic-like effect of the highest dose of anandamide. Immunohistochemistry revealed that CB1 receptors were present primarily on axonal fibers, while TRPV1 receptors were found almost exclusively surrounding the perikarya in DMH.


The present results suggest that anandamide exerts a panicolytic-like effect in the DMH by activation of CB1 receptors and that TRPV1 receptors are related to the lack of effect of the highest dose of anandamide.


Dorsomedial hypothalamus Defensive behavior Anandamide CB1 cannabinoid receptor TRPV1 channel 



The authors would like to thank Daoud Hibrahim Elias Filho for expert technical assistance with the immunohistochemistry procedure. D.H. Elias-Filhos was the recipient of technician scholarships from FAPESP (TT-2, grant 02/01497-1) and CNPq (grant 372838/2018-9).


This work was supported by the Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq) (grants 470119/2004-7 and 427397/2018-9)), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (grants 2012/03798-0, 2017/11855-8), and a Pro-Rectory of the University of São Paulo (USP) research grant (NAP-USP-NuPNE; grant IaPq2012-156-USP-12.1.25440.01.6). T. dos Anjos-Garcia was financially supported by CNPq (Scientiae Doctor Fellowship, grant 141124/2014-8) and is a postdoctorate researcher supported by FAPESP (grant 2917/22647-7). None of the organizations played further roles in the study design; the collection, analysis, or interpretation of the data; the writing of the report; or the decision to submit the paper for publication. N.C. Coimbra is a researcher (level 1A) from CNPq (grant 301341/2015-0).

Compliance with ethical standards

The experimental procedures were approved by the Commission of Ethics in Animal Experimentation (CONCEA process 227/2014) of the Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP).

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Neuroanatomy and Neuropsychobiology, Department of PharmacologyRibeirão Preto Medical School of the University of São Paulo (FMRP-USP)Ribeirão PretoBrazil
  2. 2.NAP-USP-Neurobiology of Emotions Research Centre (NuPNE)Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)Ribeirão PretoBrazil
  3. 3.Ophidiarium LNN-FMRP-USP/INeCRibeirão Preto School of Medicine of the University of São Paulo (FMRP-USP)Ribeirão PretoBrazil
  4. 4.Behavioural Neuroscience Institute (INeC)Ribeirão PretoBrazil

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