Reversal of cocaine-induced planarian behavior by parthenolide and related sesquiterpene lactones.
Submitted by Oné R Pagán on
Title | Reversal of cocaine-induced planarian behavior by parthenolide and related sesquiterpene lactones. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Pagán, OR, Rowlands, AL, Azam, M, Urban, KR, Bidja, AH, Roy, DM, Feeney, RB, Afshari, LK |
Journal | Pharmacol Biochem Behav |
Volume | 89 |
Issue | 2 |
Pagination | 160-70 |
Date Published | 2008 Apr |
ISSN | 0091-3057 |
Keywords | Algorithms, Animals, Behavior, Animal, Chromatography, High Pressure Liquid, Cocaine, Dopamine Uptake Inhibitors, Dose-Response Relationship, Drug, Hyperkinesis, Mass Spectrometry, Motor Activity, Planarians, Santonin, Sesquiterpenes, Sesquiterpenes, Eudesmane, Spectrometry, Mass, Electrospray Ionization |
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, 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. |
DOI | 10.1016/j.pbb.2007.12.008 |
Alternate Journal | Pharmacol. Biochem. Behav. |
PubMed ID | 18222535 |