Reversal of cocaine-induced planarian behavior by parthenolide and related sesquiterpene lactones.
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, beta-eudesmol, decreased planarian motility in a concentration-dependent manner. Only cocaine induced C-like hyperkinesia. At concentrations that did not show any motility decrease, parthenolide, costunolide and santonin, but not beta-eudesmol, significantly reduced the cocaine-induced motility decrease and C-like hyperkinesia, in a concentration-dependent manner. Furthermore, parthenolide, 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 microM), was able to alleviate the SL-, but not the beta-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.
Pagán
Oné R
OR
Department of Biology, West Chester University, West Chester, PA 19383-2112, United States. opagan@wcupa.edu
Rowlands
Amanda L
AL
Azam
Mahrukh
M
Urban
Kimberly R
KR
Bidja
Apurva H
AH
Roy
Danielle M
DM
Feeney
Ryan B
RB
Afshari
Lilly K
LK
D000465:Algorithms; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000139:chemically induced / Q000523:psychology; D013058:Mass Spectrometry; D009043:Motor Activity / Q000187:drug effects; D010932:Planarians / Q000502:physiology*; D012500:Santonin / Q000494:pharmacology; D012717:Sesquiterpenes / Q000032:analysis / Q000494:pharmacology*; D045787:Sesquiterpenes, Eudesmane / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D007783:Lactones
D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D012500:Santonin; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; C002669:parthenolide; C051082:beta-eudesmol; C002602:costunolide; D007783:Lactones