Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait.

M Rodríguez-Arias,C Manzanedo,J Miñarro,M A Aguilar,C Roger-Sánchez,I Vilanova,N Revert

doi:10.1155/2016/6481862

M Rodríguez-Arias, C Manzanedo + Show 5 more

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https://doi.org/10.1155/2016/6481862

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Abstract

Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP) induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS) in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p.) in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg), or cannabinoid antagonist rimonabant (1 mg/kg) and were subsequently conditioned with WIN 55212-2 (0.05 mg/kg, i.p.) or cocaine (1 or 6 mg/kg, i.p.). Only HNS mice conditioned with the 0.075 mg/kg dose acquired CPP with WIN 55212-2. Adolescent exposure to this cannabinoid agonist increased the rewarding effects of 1 mg/kg of cocaine in both HNS and LNS mice, and in HNS mice it also increased the reinstating effect of a low dose of cocaine. Our results endorse a role for individual differences such as a higher propensity for sensation-seeking in the development of addiction.

Highlights

Drug addiction is a multifactorial disorder caused by the interaction of individual and environmental factors
Animal models are a vital tool for increasing our understanding of the behavioural traits and environmental events associated with the individual vulnerability of subjects to repeated drug consumption and how these factors interact to facilitate the development of drug addiction
The results of the present study demonstrate for the first time that adolescent high novelty seeker (HNS) mice are more vulnerable to the rewarding effects of cannabinoids

Summary

Introduction

Drug addiction is a multifactorial disorder caused by the interaction of individual and environmental factors. Among the underlying factors that contribute to an enhanced predisposition to drug addiction are the existence of a vulnerable personality or phenotype [1,2,3,4,5], early exposure to drugs of abuse [6,7,8], and the presence of adverse environmental conditions such as exposure to stress [9,10,11,12]. Evidence suggests that individual differences in susceptibility to addiction involve integrated neurocircuits underlying stress, reward, and behavioural inhibitory processes [9]. The characteristic behaviour of adolescents (impulsivity, emotional liability, increased risktaking, enhanced novelty-seeking, etc.) that can favour drug use is due to this lack of prefrontal cortical maturation and hyperactivity of limbic structures involved in the processing of rewarding, emotional, and stressful stimuli, such as the nucleus accumbens (NAcc) and amygdala [14, 15]

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