The peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that has been linked to the modulation of several physiological functions, including the sleep–wake cycle. The PPARα recognizes as endogenous ligands the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which in turn, if systemically injected, they exert wake-promoting effects. Moreover, the activation of PPARα by the administration of OEA or PEA increases the extracellular contents of neurotransmitters linked to the control of wakefulness; however, the role of PPARα activated by OEA or PEA on additional biochemicals related to waking regulation, such as acetylcholine (ACh) and 5-hydroxytryptamine (5-HT), has not been fully studied. Here, we have investigated the effects of treatments of OEA or PEA on the contents of ACh and 5-HT by using in vivo microdialysis techniques coupled to HPLC means. For this purpose, OEA or PEA were systemically injected (5, 10 or 30 mg/kg; i.p.), and the levels of ACh and 5-HT were collected from the basal forebrain, a wake-related brain area. These pharmacological treatments significantly increased the contents of ACh and 5-HT as determined by HPLC procedures. Interestingly, PPARα antagonist MK-886 (30 mg/kg; i.p.) injected before the treatments of OEA or PEA blocked these outcomes. Our data suggest that the activation of PPARα by OEA or PEA produces significant changes on ACh and 5-HT levels measured from the basal forebrain and support the conclusion that PPARα is a suitable molecular element involved in the regulation of wake-related neurotransmitters.

中文翻译：

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油酰乙醇酰胺或棕榈酰乙醇酰胺给药后乙酰胆碱和 5-羟色胺的体内脑水平由 PPARα 参与介导

过氧化物酶体增殖物激活受体 α (PPARα) 是一种核受体，与多种生理功能的调节有关，包括睡眠-觉醒周期。PPARα 将脂质油酰乙醇酰胺 (OEA) 和棕榈酰乙醇酰胺 (PEA) 识别为内源性配体，反过来，如果全身注射，它们会发挥唤醒促进作用。此外，通过施用 OEA 或 PEA 激活 PPARα 增加了与控制觉醒相关的神经递质的细胞外含量；然而，OEA 或 PEA 激活的 PPARα 对与清醒调节相关的其他生化物质的作用，如乙酰胆碱 (ACh) 和 5-羟色胺 (5-HT)，尚未得到充分研究。这里，我们使用体内微透析技术结合 HPLC 手段研究了 OEA 或 PEA 处理对 ACh 和 5-HT 含量的影响。为此，全身注射 OEA 或 PEA（5、10 或 30 毫克/千克；腹腔注射），并从基底前脑（与觉醒相关的大脑区域）收集乙酰胆碱酯酶和 5-HT 的水平。这些药理处理显着增加了 ACh 和 5-HT 的含量，如通过 HPLC 程序确定的。有趣的是，在 OEA 或 PEA 治疗之前注射 PPARα 拮抗剂 MK-886 (30 mg/kg；ip) 阻止了这些结果。