Behavioural and pharmacological characterization of a novel cannabinomimetic adamantane-derived indole, APICA, and considerations on the possible misuse as a psychotropic spice abuse, in C57bl/6J mice

Abstract

The novel adamantane derivative APICA (N-(adamantan-1-yl)-1-pentyl-1H-indole-3-carboxamide) was recently identified as a cannabinomimetic indole of abuse. Despite its novel structure, APICA recalls cannabinomimetic indoles, such as representative member JWH-018.In present study, the effects of APICA (1-3 mg/kg, i.p.) were tested in C57BL/6J mice, in the Tetrad task which includes the assessment of: body temperature; locomotor activity and behavioural reactivity; nociception; motor coordination; declarative memory. Furthermore, pre-treatment with the CB1 antagonist AM251 (3 mg/kg, i.p.) or the CB2 antagonist AM630 (3 mg/kg, i.p.) was carried out to characterize APICA activity.Our results show that APICA was able to dose-dependently decrease locomotor activity and behavioural reactivity in the open field, whereas only the highest dose was able to induce hypothermia, analgesia, motor incoordination and recognition memory impairment, with respect to vehicle (p < 0.01; p < 0.001).The pretreatment with the CB1 antagonist AM251 elicited an increase in body temperature, total distance travelled in the open field, latency to fall down in the Rotarod, and a decrease in tail flick latency (p < 0.05; p < 0.01). On the other hand, pretreatment with AM630 did not induced significant differences on APICA effects.This study supports preliminary reports on APICA cannabinomimetic properties, extending its detrimental effects on cognitive function. Moreover, these properties can be attributed to the CB1 receptor activity, indicating APICA as a selective CB1 receptor agonist

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“…The open-field arena is a Plexiglas square box (44 × 44 × 44 cm where locomotor activity and explorative behavior were measured) by employing an automatic video-tracking system (AnyMaze, Ugo Basile, Italy), in a mean light- (100 lx) illuminated chamber. Each experimental session lasted 5 min (Cannizzaro et al, 2016 ). The video-tracking system produces a quali-quantitative mapping of the motor pattern, measuring total distance traveled (TDT, m), as a measure of locomotor activity in a novel environment.…”

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“…SC demonstrates also interactions with other transmission systems, namely µ-opioid [55], glutamate and GABA [56]. Meanwhile, for some SC agents abuse potential contributes also to alteration in neurobiological function, cognitive potency or behaviour without significant influence on rewarding or reinforcing systems [57][58]. Overall, SC activity at non-cannabinoid receptors may well contribute to the complex clinical effects observed [5].…”

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