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首页> 外文期刊>Frontiers in Neuropharmacology >Integrin αVβ3 Function Influences Citalopram Immobility Behavior in the Tail Suspension Test
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Integrin αVβ3 Function Influences Citalopram Immobility Behavior in the Tail Suspension Test

机译：整合素αVβ3功能影响尾悬悬吊中西酞普兰的固定行为

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Human studies first identified genetic and expression interactions between integrin β3 and serotonin (5-HT) transporter (SERT) genes. This association has been further strengthened by our discovery that integrin β3-containing receptors (αvβ3) physically interact with, and thereby define, a subpopulation of SERTs that may represent the main target of selective serotonin reuptake inhibitors (SSRIs). In this study, we examine how integrin αvβ3 function influences the behavioral response to the highly selective serotonin reuptake inhibitor citalopram in the tail suspension test. Mice bearing a conditional deletion of the integrin β3 gene in neurons, or those expressing a constitutively active αvβ3 receptor, have decreased sensitivity to citalopram, when compared to wild-type littermates. To identify potential signaling pathways downstream of integrin αvβ3 that could be altered in these mouse lines, and consequently influence citalopram response in vivo, we performed antibody array analyses of midbrain synaptosomes isolated from mice bearing genetically altered integrin β3. We then pharmacologically targeted focal adhesion (FAK) and extracellular-signal-regulated (ERK) kinases and determined that FAK and ERK activity are critical for the actions of citalopram. Taken together, our studies have revealed a complex relationship between integrin αvβ3 function, SERT-dependent 5-HT uptake, and the effective dose of citalopram in the TST, thus implicating a role for integrin signaling pathways in the behavioral response to SSRIs.
机译：人体研究首先确定了整联蛋白β3和5-羟色胺（5-HT）转运蛋白（SERT）基因之间的遗传和表达相互作用。我们的发现进一步增强了这种联系，因为发现包含整联蛋白β3的受体（αvβ3）与SERT的亚群发生物理相互作用，从而定义了这些亚群，它们可能代表选择性5-羟色胺再摄取抑制剂（SSRI）的主要靶标。在这项研究中，我们研究了整联蛋白αvβ3的功能如何在尾部悬吊试验中影响对高选择性5-羟色胺再摄取抑制剂西酞普兰的行为反应。与野生型同窝仔相比，神经元中带有整合素β3基因有条件缺失的小鼠或表达组成性活性αvβ3受体的小鼠对西酞普兰的敏感性降低。为了鉴定整合素αvβ3下游可能在这些小鼠品系中发生改变的潜在信号通路，从而影响西酞普兰的体内反应，我们对分离自携带遗传改变的整合素β3的小鼠的中脑突触体进行了抗体阵列分析。然后，我们在药理学上靶向粘着斑（FAK）和细胞外信号调节（ERK）激酶，并确定FAK和ERK活性对于西酞普兰的作用至关重要。综上所述，我们的研究揭示了整合素αvβ3功能，SERT依赖的5-HT摄取与西酞普兰在TST中的有效剂量之间存在复杂的关系，从而暗示了整合素信号传导途径在对SSRI的行为反应中的作用。

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