Cocaine abuse has an enormous cost to society at many levels, usually measured in billions of dollars. The flatworm planaria shows considerable promise as a model to study cocaine effects in biological systems. This organism has a well-developed nervous system, including a rudimentary brain, and every major neurotransmitter system described in mammals, including humans. Additionally, its nerve cells share many structural similarities with vertebrate neurons. Several recent studies dealing with various effects of cocaine on planarian worms have been published. Here we report that parthenolide, a naturally-occurring compound, alleviated a specific cocaine-induced behavior in planarians. Using an adaptation of published behavioral protocols, we have determined that acute exposure to cocaine decreased planarian motility in a concentration-dependent manner, with an Inhibitory Concentration at 50 % (IC50) of 67 ± 7 µM. In the presence of 50 µM parthenolide, the IC50 for cocaine significantly increases to 365 ± 32 µM. By itself, parthenolide at concentrations ≤ 50 µM did not elicit any behavioral effects in planaria. This alleviation by parthenolide was concentration-dependent. In experiments using a fixed concentration of cocaine at 100 µM, parthenolide displayed an Effective Concentration at 50 % (EC50) value of 7.6 ± 0.8 µ and achieved complete alleviation at a concentration of 50 µM. To our knowledge, this is the first compound that completely alleviates cocaine-induced effects in an in vivo model. These findings can lead to compounds that may alleviate the behavioral or toxic effects of cocaine in humans. [ABSTRACT FROM AUTHOR]
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