Reducing effect of intragastrically administered saikosaponin A on alcohol and sucrose self-administration in rats

Abstract

Saikosaponin A (SSA) is an active ingredient of the Asian medicinal herb, Bupleurum falcatum L. When administered via the intraperitoneal (i.p.) route, SSA suppressed multiple addictive-like behaviours, including operant alcohol self-administration, in rodents. It is unknown if these effects are retained after intragastric (i.g.) administration, a desirable prerequisite for a compound with therapeutic potential. To fill this gap, i.g. SSA (0, 50, and 100 mg/kg) was tested in Sardinian alcohol-preferring (sP) rats trained to lever-respond for oral alcohol. SSA reduced lever-responding and amount of self-administered alcohol. However, when compared to i.p. SSA, i.g. SSA resulted to be markedly less potent and effective, leading to hypothesise a major involvement of first-pass metabolism. Finally, and in agreement with previous data on the suppressing effect of i.p. SSA on behaviours motivated by highly palatable foods, i.g. SSA (0, 50, and 100 mg/kg) reduced oral sucrose self-administration in a separate set of sP rats. Experimental sectionThe experimental procedures employed in this study fully complied with European Directive no. 2010/63/EU and subsequent Italian Legislative Decree no. 26, March 4, 2014, on the "Protection of animals used for scientific purposes". Chemical analysis equipmentAnalytical HPLC/ESI-MS(negative) chromatograms of the n-butanol-soluble fraction were acquired using an Agilent Technologies 1200-series HPLC/MS system (Santa Clara, CA, USA). The purity test for SSA conducted on Dionex UltiMate 3000 (Thermo Scientific) equipped with the Phenomenex Luna C18(2) column (250 x 4.6 mm, 5 µm). HPLC isolation was performed on a Gilson 321 (Middleton, WI, USA) equipped with