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Sex‐specific impact of repeated adolescent vapour exposure to JWH‐018 on dopamine response, behaviour and pharmacokinetics across adolescence and adulthood

Year: 2025

Type: article

Abstract: BACKGROUND AND PURPOSE: Alarming trends show that vaping e-cigarettes containing synthetic cannabinoid receptor agonists, such as JWH-018, is increasing among youth. However, the effects of these trends are unclear in both sexes. We therefore characterized the neuropharmacological effects of adolescent JWH-018 inhalation in male and female rats. EXPERIMENTAL APPROACH: qd) for 21 days. During vapour exposure, JWH-018 and main metabolite plasma levels, body weight, locomotion and ultrasonic vocalizations were measured at different time points. During drug-free period, behavioural (withdrawal signs, anxiety and repetitive-like behaviour) and microdialysis (NAc shell/mPFC dopamine responsiveness to intraoral chocolate, taste reactivity) studies were performed 24 h and 7 days after last JWH-018 inhalation, respectively. KEY RESULTS: Repeated adolescent JWH-018 inhalation induced sex-dependent effects with (i) higher plasma levels in males; (ii) increased body weight gain and withdrawal signs in females; (iii) transient hypolocomotion in females and dose-dependent biphasic locomotion in males; (iv) higher taste aversion in male; (v) sex- and dose-dependent adaptive changes of NAc shell and mPFC dopamine to single/repeated chocolate exposure in early adulthood, as follows: in the NAc shell, either low or high dose decreased dopamine sensitivity to chocolate in males, low dose abolished habituation whereas high dose blunted dopamine responsiveness in females; in the mPFC, the low dose blunted responsiveness in male and induced habituation in females while the high dose induced habituation only in males. CONCLUSION AND IMPLICATIONS: Using highly translational models, we showed that the impact of adolescent JWH-018 inhalation differs between sexes.

Source: British Journal of Pharmacology

DOI: 10.1111/bph.70223