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Chunk #37 — 4. Discussion

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PPAR agonists regulate brain gene expression: relationship to their effects on ethanol consumption.
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2) as a ratio of dose to the half maximal effective concentration (EC50) required for subtype-specific action 30, 65 (Table S6). Fenofibrate and tesaglitazar were used at about 5–7 times the human dose whereas bezafibrate was equivalent to the human dose. We did not use higher doses of bezafibrate because liver changes in mice have been reported with 20 mg/kg body weight 24. The dose/EC50 ratio shows that fenofibrate has selectivity for PPARα (8.3) over γ (0.6), and tesaglitazar has selectivity for γ (6) over α (0.05). In contrast, the ratios for bezafibrate are lower for all three PPARs (0.8 for α, 1.4 for γ and 0.7 for β/δ) (Table S6). It is possible that the dose of bezafibrate used provided less activation of PPARs, possibly accounting for its weaker effects.