Canna~Fangled Abstracts

Augmented anandamide signalling in the substantia nigra pars reticulata mediates panicolytic-like effects in mice confronted by Crotalus durissus terrificus pit vipers

By June 2, 2022June 21st, 2022No Comments

. 2022 Jun 2.

doi: 10.1007/s00213-022-06127-3.

Online ahead of print.
Rafael C Almada 1 2, Luiz Luciano Falconi-Sobrinho 1 3 4 5, Juliana A da Silva 1 3, Carsten T Wotjak 6 7, Norberto C Coimbra 8 9 10 11
Affiliations 

Abstract

Rationale: The endocannabinoid modulation of fear and anxiety due to the on-demand synthesis and degradation is supported by a large body of research. Although it has been proposed that anandamide (AEA) in the substantia nigra pars reticulata (SNpr) seems to be important for the organisation of innate fear-related behaviours, a role for endogenous AEA has yet to be clarified.

Methods: Mice were treated with the fatty acid amide hydrolase (FAAH) selective inhibitor URB597 at different concentrations (0.01, 0.1, 1 nmol/0.1 µL) in the SNpr and confronted by rattlesnakes (Crotalus durissus terrificus). The most effective dose of URB597 (1 nmol) was also preceded by microinjections of the CB1 receptor antagonist AM251 (0.1 nmol) into the SNpr, and mice were then confronted by the venomous snake.

Results: URB597 (0.1 and 1 nmol) in the SNpr decreased the expression of defensive behaviours such as defensive attention, escape, and time spent inside the burrow of mice confronted by rattlesnakes. Moreover, pretreatment of SNpr with AM251 suppressed these antiaversive effects of URB597 in this midbrain structure.

Conclusion: Overall, these data clearly indicate that the panicolytic consequences of endogenous AEA enhancement in the SNpr are mediated by CB1 receptor signalling.

Keywords: Anandamide, Crotalus durissus terrificus venomous pit viper, Panic attacks, Prey vs. venomous snake paradigm, Substantia nigra pars reticulata (SNpr), URB597

References

    1. Almada RC, Coimbra NC (2015) Recruitment of striatonigral disinhibitory and nigrotectal inhibitory GABAergic pathways during the organization of defensive behavior by mice in a dangerous environment with the venomous snake Bothrops alternatus (Reptilia, Viperidae). Synapse 69:299–313. https://doi.org/10.1002/syn.21814 – DOI – PubMed
    1. Almada RC, Dos Anjos-Garcia T, da Silva JA et al (2021) 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. Behav Brain Res 401:112996. https://doi.org/10.1016/j.bbr.2020.112996 – DOI – PubMed
    1. Almada RC, Genewsky AJ, Heinz DE et al (2018) Stimulation of the nigrotectal pathway at the level of the superior colliculus reduces threat recognition and causes a shift from avoidance to approach behavior. Front Neural Circuits 1:1–27. https://doi.org/10.3389/fncir.2018.00036 – DOI
    1. Almada RC, Roncon CM, Elias-Filho DH, Coimbra NC (2015) Endocannabinoid signaling mechanisms in the substantia nigra pars reticulata modulate GABAergic nigrotectal pathways in mice threatened by urutu-cruzeiro venomous pit viper. Neuroscience 303:503–514. https://doi.org/10.1016/j.neuroscience.2015.06.048 – DOI – PubMed
    1. Biagioni AF, de Freitas RL, da Silva JA et al (2013) Serotonergic neural links from the dorsal raphe nucleus modulate defensive behaviours organised by the dorsomedial hypothalamus and the elaboration of fear-induced antinociception via locus coeruleus pathways. Neuropharmacology 67:379–394. https://doi.org/10.1016/j.neuropharm.2012.10.024 – DOI – PubMed

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