The LPA1 receptor, one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts, is likely involved in promoting normal emotional behaviours. Current data suggest that the LPA-LPA1-receptor pathway may be involved in mediating the negative consequences of stress on hippocampal function. However, to date, there is no available information regarding the mechanisms whereby the LPA1 receptor mediates this adaptation. To gain further insight into how the LPA-LPA1 pathway may prevent the negative consequences of chronic stress, we assessed the effects of the continuous delivery of LPA on depressive-like behaviours induced by a chronic restraint stress protocol. Because a proper excitatory/inhibitory balance seems to be key for controlling the stress response system, the gene expression of molecular markers of excitatory and inhibitory neurotransmission was also determined. In addition, the hippocampal expression of mineralocorticoid receptor genes and glucocorticoid receptor genes and proteins as well as plasma corticosterone levels were determined. Contrary to our expectations, the continuous delivery of LPA in chronically stressed animals potentiated rather than inhibited some (e.g., anhedonia, reduced latency to the first immobility period), though not all, behavioural effects of stress. Furthermore, this treatment led to an alteration in the genes coding for proteins involved in the excitatory/inhibitory balance in the ventral hippocampus and to changes in corticosterone levels. In conclusion, the results of this study reinforce the assumption that LPA is involved in emotional regulation, mainly through the LPA1 receptor, and regulates the effects of stress on hippocampal gene expression and hippocampus-dependent behaviour.

中文翻译：

---

LPA1受体和慢性应激：对行为和海马兴奋/抑制平衡相关基因的影响。

LPA1受体是溶血磷脂酸通过其作用的六个特征性G蛋白偶联受体（LPA1-6）之一，可能与促进正常的情绪行为有关。当前数据表明，LPA-LPA1-受体途径可能参与介导应激对海马功能的负面影响。但是，迄今为止，尚无有关LPA1受体介导这种适应的机制的可用信息。为了进一步了解LPA-LPA1途径如何预防慢性应激的不良后果，我们评估了连续递送LPA对慢性束缚应激协议诱发的抑郁样行为的影响。由于适当的兴奋/抑制平衡似乎是控制压力反应系统的关键，还确定了兴奋性和抑制性神经传递的分子标志物的基因表达。另外，测定了盐皮质激素受体基因和糖皮质激素受体基因和蛋白在海马中的表达以及血浆皮质酮水平。与我们的预期相反，在长期应激的动物中，LPA的持续递送增强了而不是抑制了某些行为（例如，快感缺乏症，降低了至第一个固定期的潜伏期），尽管并非全部，但都是应激的行为效应。此外，这种治疗导致腹侧海马兴奋/抑制平衡所涉及的蛋白质编码基因的改变，以及皮质酮水平的变化。总而言之，这项研究的结果强化了LPA参与情绪调节的假设，