Mechanisms Associated with Age and Sex Modulate Motor like Tics Via the CB2 Cannabinoid Receptor

Описание: TIC-CON 2023: Mechanisms associated with age and sex modulate motor-like tics via the CB2 cannabinoid receptor

Presenter: Sharon Anavi-Goffer, PhD - University of Aberdeen, Aberdeen, UK

The effects of HU-308, a selective cannabinoid CB2 receptor agonist, on motor-like tics were studied in the presence or absence of 2,5-dimethoxy-4-iodoamphetamine (DOI), a highly potent agonist of the serotonin 5-HT2A/2C receptors. The effects of HU-308 on head twitch response (HTR; central motor-like tic), ear scratch response (ESR; urge-like response) and grooming behavior (caudally located peripheral motor-like tic) were compared between wildtype and CB2 receptor knockout (CB2-/-) mice. The frequency of DOI-induced repetitive behaviors was higher in CB2-/- than wildtype mice. HU-308 increased DOI-induced ESR and grooming behavior in adult CB2-/- mice. In healthy juvenile males, in the absence of DOI, HU-308 significantly increased HTR. But in the presence of DOI (model of motor tics), HU-308 inhibited HTR and ESR. In left prefrontal cortex of juvenile male mice, DOI increased transcript expression of the CB2 receptor, but reduced fatty acid amide hydrolase (FAAH) and α/β-hydrolase domain-containing 6 (ABHD6), which hydrolyzes the endogenous cannabinoid 2-arachidonoylglycerol (2-AG), expression levels. The intensity of the effects of HU-308 in females was lower than in males: (1) HU-308 had a lower or no effect on HTR in juvenile females; (2) HU-308 significantly decreased basal grooming behavior in juvenile females but not in males; (3) HU-308 (0.2 mg/kg) significantly inhibited DOI-induced HTR and grooming behavior in females but not in males.