Search

Abstract: Here we report the prevention and reversal of cocaine-induced behaviors in planarian worms by parthenolide and two related cyclic sesquiterpene lactones (SL), costunolide and santonin. Using established protocols, we studied two cocaine-induced behavioral effects in planaria; the induction of motility decrease and the induction of C-like hyperkinesia. Cocaine, parthenolide, costunolide, santonin, and a lactone-less cyclic sesquiterpene, β-eudesmol, decreased planarian motility in a concentration-dependent manner. Only cocaine induced C-like hyperkinesia. At concentrations that did not show any motility decrease, partenolide, costunolide and santonin, but not β-eudesmol, significantly reduced the cocaine-induced motility decrease and C-like hyperkinesia, in a concentration-dependent manner. Furthermore, partenolide, costunolide and santonin were able to rescue planaria from C-like hyperkinesia, after the worms were exposed to cocaine. Conversely, cocaine at a concentration that did not show any measurable effects (10 µM), was able to alleviate the SL-, but not the β-eudesmol-induced motility decrease. Liquid Chromatography/Mass Spectrometry experiments demonstrated that cocaine does not interact directly with any of the cyclic sesquiterpenoids, which suggests specific biochemical targets for these compounds in planarians. Our data suggests a common binding site for cocaine and the sesquiterpene lactones in planarians. [Copyright &y& Elsevier]

Abstract: We recently reported that parthenolide and related sesquiterpene lactones are able to prevent and reverse behavioral responses in planarian worms induced by acute cocaine exposure. Previous reports indicate that when planarians are chronically exposed to µM concentrations of cocaine, they display stereotypical withdrawal-like behaviors when the cocaine is removed. Here we report that parthenolide prevents this cocaine-induced expression of planarian withdrawal-like behaviors. [Copyright &y& Elsevier]