サルにおけるスクボレキサントのアルコール探索および自己投与への影響評価

The orexin receptor system is gaining interest as a potential therapeutic target to reduce heavy alcohol drinking. Studies of orexin-1 and orexin-2 receptor antagonists have shown decreased alcohol seeking and self-administration in rodents. This study examined if acute treatment with the dual orexin receptor antagonist suvorexant would decrease alcohol seeking and self-administration in a nonhuman primate chronic drinking model.

Subjects were six baboons with extensive histories of chronic alcohol self-administration under an operant chained schedule of reinforcement. Sessions consisted of three components (modeling alcohol anticipation, seeking, consumption), each with distinct stimuli and behavioral contingencies to gain access to and self-administer alcohol. Suvorexant (0, 0.032, 0.1, 0.32, 0.6, 1.0mg/kg, p.o.) was acutely administered 60min before the session. Linear mixed-effect models were used to evaluate suvorexant effects on alcohol seeking (fixed interval [FI] latency and responses) and self-administration (Fixed ratio [FR] responses, alcohol volume and g/kg intake).

No significant effects of acute suvorexant were observed on alcohol seeking (p > .62). A significant effect of suvorexant was observed for self-administration responses (p = .04), but not for alcohol g/kg intake (p = .08). Both outcomes demonstrated a dose-related biphasic curve with a modest decrease in self-administration after 0.1mg/kg suvorexant and modest increase in self-administration after 1.0mg/kg suvorexant.

Low dose suvorexant may acutely reduce drinking, but the magnitude of change may not be clinically meaningful. Higher doses of suvorexant may worsen heavy drinking. These data do not support suvorexant use to reduce alcohol intake during ongoing use.