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

Abstract

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 GABA B receptor agonist and exert multiple pharmacological effects. Given the role of the GABA B 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 GABA B receptor antagonist, SCH50911, and potentiated by co-administration of the positive allosteric modulator of the GABA B 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 GABA B receptor agonist; they also indicate that ISL reproduced the suppressing effects of the prototypic GABA B receptor agonist, baclofen, on multiple alcohol-related behaviors in rodents.

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