The Attenuation of Alcohol and Nicotine Induced Behaviors in Drosophila melanogaster by Sinomenine

Abstract

The purpose of this experiment is to determine the efficacy of Sinomenine, an opioid receptor antagonist, in attenuating ethanol and nicotine induced behaviors in Drosophila melanogaster. While ethanol and nicotine are quite different in their direct mechanism of action, current research suggests that opiate reward, CREB-mediated transcription, and long-term potentiation are common pathways implicated in the development of various addictions. Due to its ability to antagonize the mu-opioid receptor, Sinomenine prevents endorphin binding, drug-induced CREB transcription, and consequent increase in dopamine production by tyrosine hydroxylase that leads to euphoria and addiction. Sinomenine may be particularly promising over other opioid receptor antagonists for sedative addictions due to its opioid-receptor independent anxiolytic effects. In a CAFE assay performed to measure preference through consumption of ethanol or nicotine, Sinomenine reverses both naive and conditioned preference for ethanol, as well as conditioned nicotine aversion. Measuring locomotion, Sinomenine attenuated both the ethanol and nicotine induced decreases in negative geotaxis exhibition in Drosophila melanogaster. Quantifying olfactory preference, Sinomenine reversed conditioned odor preference in a Y-maze, but not naive preference. Reflecting its effects on the CREB pathway, Sinomenine inhibited a nicotine-induced increase in cAMP, but did not significantly affect cAMP levels in ethanol treated Drosophila. According to these results, Sinomenine is particularly effective in attenuating conditioned ethanol or nicotine-induced behavior, and produces mixed results in terms of naive exposure. The natural chemosensory preferences or aversion of ethanol and nicotine may be independent of the CREB pathway, while developed preference may be directly dependent on it.