Effect of saikosaponin A, one of the main bioactive triterpenoids of Bupleurum falcatum, on alcohol binge-like drinking in rodents

Background: Previous work demonstrated that administration of saikosaponin A (SSA), one of the major components of the roots of Bupleurum falcatum, reduced oral alcohol self-administration, a validated measure of the reinforcing and motivational properties of alcohol, in Sardinian alcohol-preferring (sP) rats. Objectives: To evaluate whether SSA ability to reduce the reinforcing and motivational properties of alcohol extends to well-established binge-like drinking paradigms, characterized by intoxicating drinking patterns, in sP rats and C57BL/6J mice. Methods: Male sP rats (n = 48) were exposed to the 4-bottle [10%, 20%, and 30% (v/v)] alcohol vs water choice regimen, with limited and unpredictable time to access to alcohol. Male C57BL/6J mice (n = 56) were subjected to a single-bottle, 20% alcohol "drinking in the dark" protocol, initiated 3 hours into the dark phase. In both experiments, SSA (0, 1, 2, or 4 mg/kg) was administered acutely and intraperitoneally 15 min before the start of the drinking session. SSA was also tested on spontaneous locomotor activity in alcohol-naive sP rats (n = 48) and C57BL/6J mice (n = 39). Results: Alcohol binge-like drinking was prevented by administration of 2 and 4 mg/kg SSA in sP rats (p < .05; p < .005) and C57BL/6J mice (p < .005; p < .0001). However, the results of the locomotor activity experiments indicated that specificity of the reducing effect of SSA on alcohol intake was limited to sP rats and observed only at the dose of 2 mg/kg (p > .05). Conclusion: Overall, our findings support the potential of SSA as a treatment for binge alcohol drinking.