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Objective: Capsaicin, the pungent analgesic substance of hot peppers which produces a burning sensation and pain is known to affect Substance P and central opioid activities. This experiment was designed to test the effect of capsaicin on alcohol consumption in C57BL/6 and DBA/2 mice. These two strains are known to differ in both their alcohol consumption and their endogenous opioid distribution and response to alcohol. It is hypothesized that this effect may be mediated by both increases Substance P and decreases beta-endorphin., Methods: After i.p. administration of 0.01 and 0.001 mg/kg of capsaicin with a vehicle or the vehicle alone as the control for eight days in C57BL/6 and DBA/2 mice on limited access alcohol model, Capsaicin's effects on 2-hour alcohol, 22-hours water, 24-hours food intake and body weight were studied., Results: In this study, as expected, C57BL/6 mice drank significantly more alcohol than DBA/2 mice under baseline conditions. Capsaicin at both doses tested significantly reduced baseline alcohol consumption in C57BL/6 but not DBA/2 mice. These effects were selective for alcohol as capsaicin did not disrupt food or water consumption., Conclusion: These results demonstrate that capsaicin differentially affects those mechanisms underlying alcohol consumption in two strains of mice known to differ in their preference for and consumption of alcohol. This effect is hypothesized to be related to differences in the response of the endogenous opioid system.