CB₁ receptor signalling mediates cannabidiol-induced panicolytic-like effects and defensive antinociception impairment in mice threatened by Bothrops jararaca lancehead pit vipers

de Paula Rodrigues, Bruno Mangili
Coimbra, Norberto Cysne

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

Norberto Cysne Coimbra, Laboratório de Neuroanatomia and Neuropsicobiologia, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Avenida Bandeirantes 3900, Ribeirão Preto, São Paulo 14049-900, Brasil. Email: [email protected]

Journal of Psychopharmacology 36(12):p 1384-1396, December 2022. | DOI: 10.1177/02698811221115755

Background:

Cannabis sativa-derived substances such as cannabidiol (CBD) have attracted increasing clinical interest and consist in a new perspective for treating some neurological and psychiatric diseases.

Aims:

The aim of this work was to investigate the effect of acute treatment with CBD on panic-like defensive responses displayed by mice threatened by the venomous snake Bothrops jararaca.

Methods:

Mice were habituated in the enriched polygonal arena for snake panic test. After recording the baseline responses of the tail-flick test, the prey were pretreated with intraperitoneal (i.p.) administrations of the endocannabinoid type 1 receptor (CB₁) antagonist AM251 (selective cannabinoid 1 receptor antagonist with an IC50 of 8 nM) at different doses, which were followed after 10 min by i.p. treatment with CBD (3 mg/kg). Thirty minutes after treatment with CBD, mice were subjected to confrontations by B. jararaca for 5 min, and the following defensive responses were recorded: risk assessment, oriented escape behaviour, inhibitory avoidance and prey-versus-snake interactions. Immediately after the escape behaviour was exhibited, the tail-flick latencies were recorded every 5 min for 30 min.

Outcomes:

Mice threatened by snakes displayed several anti-predatory defensive and innate fear-induced antinociception responses in comparison to the control. CBD significantly decreased the risk assessment and escape responses, with a consequent decrease in defensive antinociception. The CBD panicolytic effect was reversed by i.p. treatment with AM251.

Conclusions: