Neurokinin-1 receptor antagonist rolapitant suppresses anxiety and alcohol intake produced by repeated withdrawal episodes.

Abstract

Neurokinin-1 receptor (NK1r) antagonists have been shown to suppress operant self-administration of alcohol, voluntary alcohol consumption and stress-induced reinstatement of alcohol-seeking behaviour. Considering the long half-life and anxiolytic-like properties of NK1r antagonist rolapitant, we expected that it may be an effective option for reducing anxiety and alcohol motivation during early withdrawal. Voluntary alcohol intake (two-bottles paradigm) was recorded in male Wistar rats during the three periods: 24 days (basal level), 6-day period when rats received 5 mg·kg-1 rolapitant or vehicle and 12-h period after repeated withdrawal episodes (alcohol cessation for 36 h). We found that upon intraperitoneal (i.p.) administration, rolapitant rapidly penetrated into specific rat brain regions - amygdala, hypothalamus and neocortex - implicated in the control of anxiety and reward. Rolapitant did not affect basal voluntary alcohol intake, but significantly suppressed anxiety-like behaviour and alcohol consumption following withdrawal episodes. Our findings suggest that rolapitant should be further investigated as a novel treatment option for relapse prevention in alcohol-dependent patients.