Reducing effects of isoliquiritigenin, a naturally occurring GABAB receptor agonist, on alcohol-motivated behaviors in alcohol-preferring rats

Rationale and Objectives: Glycyrrhiza glabra L. (Fabaceae; licorice) is a widely used medicinal herb known to exert protective effects against multiple neurological diseases. The flavonoid, isoliquiritigenin (ISL), is a main constituent of roots of Glycyrrhiza glabra. ISL has been reported to behave as a GABAB receptor agonist and exert multiple pharmacological effects. Given the role of the GABAB receptor in the neurobiological and pharmacological bases of alcohol use disorder, the present study investigated the effect of ISL on a series of alcohol-related behaviors in selectively bred, female Sardinian alcohol-preferring rats. Methods and Results: The collected results indicated that acute treatment with ISL (5-20 mg/kg, i.p.; 50-200 mg/kg, i.g.) decreased operant oral alcohol self-administration under both fixed and progressive ratio schedules of reinforcement and suppressed cue-induced reinstatement of alcohol seeking. ISL effect on alcohol self-administration was partially blocked by pretreatment with the GABAB receptor antagonist, SCH50911, and potentiated by co-administration of the positive allosteric modulator of the GABAB receptor, GS39783. Acute treatment with doses of ISL as high as 80 mg/kg (i.p.) did not alter spontaneous locomotor activity, suggestive of the specificity of ISL effects on alcohol-related behaviors. Conclusions: These results confirm the ability of ISL to behave in vivo as a GABAB receptor agonist; they also indicate that ISL reproduced the suppressing effects of the prototypic GABAB receptor agonist, baclofen, on multiple alcohol-related behaviors in rodents.