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

Abstract

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. 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. 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. 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. These findings suggest that the anti-aversive effect of CBD depends at least in part on the recruitment of CB1 receptors.