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

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.

Preclinical Studies of Cannabinoid Reward, Treatments for Cannabis Use Disorder, and Addiction-Related Effects of Cannabinoid Exposure

“…Rats that were exposed to THC in adolescence and then allowed to self-administer the synthetic cannabinoid WIN 55,212-2 in adulthood acquired cannabinoid selfadministration behavior more rapidly and reached higher asymptotic levels of intake under an FR1 schedule (Scherma et al, 2016a); these results might be at least partly because of THC exposure inducing cross-tolerance to the effects of WIN 55,212-2 such that exposed rats required more drug to reach a satiating effect. In conditioned place-preference studies, THC exposure increased conditioning to a cannabinoid-associated context in two experiments using mice (Hyatt and Fantegrossi, 2014;Valjent and Maldonado, 2000), but WIN 55,212-2 exposure did not (Rodriguez-Arias et al, 2016). THC exposure had no effect on conditioning to a THC-associated context in two studies using rats (Hempel et al, 2016;Wakeford et al, 2016); these studies used a procedure that combined place conditioning and taste conditioning, but place conditioning did not occur in THC-exposed rats or in vehicle-exposed controls in either experiment.…”

“…MDMA. In studies of the conditioned preference for a place associated with MDMA ('ecstasy'), exposure to the cannabinoid agonist JWH-018 did not affect conditioning in NIH Swiss mice (Hyatt and Fantegrossi, 2014), but exposure to WIN 55,212-2 did enhance conditioning in OF1 mice (Rodriguez-Arias et al, 2016).…”

“…Cocaine. Rodriguez- Arias et al (2016) found that exposure to WIN 55,212-2 enhanced conditioning of preference for a place associated with a low dose of cocaine and also made preference for a cocaine-associated place more persistent in a model of relapse, but only in mice that had been characterized as high novelty seekers in a hole-board exploration test before any drug exposure. In studies of FR1 cocaine self-administration, THC exposure did not affect cocaine intake in male rats , but exposure to CP 55,940 enhanced cocaine intake in female rats during the first week when they were switched to cocaine after being pretrained with food reinforcement (Higuera-Matas et al, 2008); the cocaine intake of the other rats in the study (nonexposed females, exposed males, and nonexposed males) caught up to the CP 55,940-exposed females after the first week (Higuera-Matas et al, 2008).…”

Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

“…One intriguing conclusion from this analysis is that even a relatively small increase in exposure to cannabis or alcohol (as detected dimensionally with KMSK scales) results in further increased odds of depression, in cases with cocaine dependence. It is known that CB1 receptor systems interact with the effects of cocaine, from preclinical and clinical studies . Alcohol and cocaine also share some downstream neurobiological effects …”

The impaired anesthesiologist: what you should know about substance abuse

“…There have been many hypotheses proposed to explain why some people develop SUD while others do not. Animal and human studies have investigated epigenetic changes 16 and novelty-seeking behaviour traits as risk factors for addiction 17,18 as well as a disproportionately strong response to dopamine-releasing drugs, whether preexisting or drug-induced. 19,20 Numerous studies have reported that self-medication of symptoms associated with comorbid psychiatric disorders is a risk factor for development of SUD, 1,14,[21][22][23] and this may be more of a risk factor for female healthcare practitioners than for their male counterparts.…”