α₇ Nicotinic acetylcholine receptor–mediated protection against ethanol-induced neurotoxicity

Abstract 

The α₇-selective nicotinic partial agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB) was examined for its ability to modulate ethanol-induced neurotoxicity in primary cultures of rat neurons. Primary cultures of hippocampal neurons were established from Long–Evans, embryonic day (E)-18 rat fetuses and maintained for 7 days. Ethanol (0–150 mM), DMXB (0–56 μM), or both were subsequently co-applied to cultures. Ethanol was added two additional times to the cultures to compensate for evaporation. After 5 days, neuronal viability was assessed with the MTT cell proliferation assay. Results demonstrated that ethanol reduces neuronal viability in a concentration-dependent fashion and that DMXB protects against this ethanol-induced neurotoxicity, also in a concentration-dependent fashion. These results support the suggestion that nicotinic partial agonists may be useful in treating binge drinking–induced neurotoxicity and may provide clues as to why heavy drinkers are usually smokers.

Keywords:  Ethanol, Neurotoxicity, Nicotinic agonists, Neuroprotection, Alcoholism, Binge drinking, MTT, GTS-21, DMXB