5HT2A Receptors are Involved in the Pharmaco-Toxicological Effects of the Synthetic Cannabinoids JWH-018 and 5F-PB22: in Vivo Studies in Mice

Abstract

Introduction: Since their first appearance on the illicit drugs market, Synthetic Cannabinoids (SCs) have been frequently detected in biological samples from patients involved in several intoxication and death cases. To date, their serious adverse effects have been primarily related to their action as potent agonist of CB1 cannabinoid receptors. However, evidence concerning the potential interaction between SCs and serotoninergic neurotransmission system has emerged. Thus, this study aims to evaluate the involvement of 5HT2A receptors in the effects provoked by these substances. Methods: The effects induced by acute systemic administration of 1-pentyl-3-(1-naphthoyl)indole (JWH-018; 1 mg/kg) and quinolin-8-yl 1-pentyfluoro-1H-indole-3-8-carboxylate (5F-PB22; 1 mg/kg) on sensorimotor (visual, acoustic and tactile) responses, pain threshold (acute mechanical and thermal nociception), core temperature, breath rate and motor performance (stepping activity), as well as their interaction with the selective 5HT2A receptors antagonist MDL100907 (0.1 mg/kg), have been evaluated in CD-1 male mice. Results: The present results pointed out that both substances deeply alter sensorimotor responses, nociceptive threshold, core temperature, breath rate and motor activity in mice. Noteworthy, pretreatment with MDL100907 at least partially prevented sensorimotor disruption, as well as antinociceptive and hypothermic effects. Conclusions: This study states the relevance of serotoninergic 5HT2A mechanisms on pharmaco-toxicological effects induced by SCs, suggesting the potential risk of increased susceptibility for psychotic-like symptoms also related to mental disorders.