Adolescent Exposure to the Synthetic Cannabinoid WIN 55212-2 Modifies Cocaine Withdrawal Symptoms in Adult Mice.

María Aguilar,M Arenas,Juan Ledesma,Marta Rodríguez-Arias,Carmen Manzanedo,Carles Penalva,José Miñarro

doi:10.3390/ijms18061326

María Aguilar, M Arenas + Show 5 more

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https://doi.org/10.3390/ijms18061326

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Abstract

Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause psychiatric symptoms, such as psychosis, cognitive impairment, anxiety, and depression. The aim of the present research was to study the consequences of adolescent exposure to cannabis on the psychiatric-like effects promoted by cocaine withdrawal in adult mice. We pre-treated juvenile mice with the cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) and then subjected them to a chronic cocaine treatment during adulthood. Following these treatments, animals were tested under cocaine withdrawal in the following paradigms: pre-pulse inhibition, object recognition, elevated plus maze, and tail suspension. The long-term psychotic-like actions induced by WIN were not modified after cocaine cessation. Moreover, the memory impairments induced by cocaine withdrawal were not altered by previous adolescent WIN intake. However, WIN pre-treatment prevented the anxiogenic effects observed after cocaine abstinence, and led to greater depressive-like symptoms following cocaine removal in adulthood. This study is the first to show the long-lasting behavioral consequences of juvenile exposure to WIN on cocaine withdrawal in adult mice.

Highlights

Products of the hemp plant Cannabis sativa—marijuana and hashish are among the illicit substances most commonly used by adolescents and young adults worldwide, and are the world’s third most popular recreational drug after ethanol (EtOH) and tobacco [1]
We demonstrated that exposure to an EtOH binge-drinking procedure during adolescence, which is not able to alter the Pre-pulse inhibition (PPI) by itself, impairs the startle reflex in mice exposed to the same cocaine withdrawal as that of the current study [55]
The current results demonstrate for the first time the long-lasting consequences of juvenile exposure to WIN on cocaine withdrawal in adult mice

Summary

Introduction

Products of the hemp plant Cannabis sativa—marijuana and hashish are among the illicit substances most commonly used by adolescents and young adults worldwide, and are the world’s third most popular recreational drug after ethanol (EtOH) and tobacco [1]. The main psychoactive component of the Cannabis sativa plant and its derivatives is ∆9-tetrahydrocannabinol (THC), which acts primarily via specific endogenous cannabinoid 1 (CB1) receptors in the brain [2,3]. Since 2008, over 160 synthetic cannabinoids have been detected in a range of different products that are sold as “legal” replacements for cannabis they are considerably more toxic than marijuana and hashish [4]. Synthetic cannabinoids are several times more potent than THC in activating cannabinoid receptors in the brain [5]. The endocannabinoid system is densely distributed in regions involved in the processing of emotional inputs, rewarding stimuli, habit formation, and higher cognitive functions, and represents a common neurobiological substrate for the addictive properties of different drugs of abuse via CB1 receptors [6,7]

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