Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
Pharmacol Rep. 2011;63(6):1349-58. doi: 10.1016/s1734-1140(11)70699-5.
We have previously reported that chronic imipramine and electroconvulsive treatments increase the α(1A)-adrenoceptor (but not the α(1B) subtype) mRNA level and the receptor density in the rat cerebral cortex. Furthermore, we have also shown that chronic treatment with citalopram does not affect the expression of either the α(1A)- or the α(1B)-adrenoceptor, indicating that the previously observed up-regulation of α(1A)-adrenoceptor may depend on the noradrenergic component of the pharmacological mechanism of action of these antidepressants. Here, we report that previous noradrenergic depletion with DSP-4 (50 mg/kg) (a neurotoxin selective for the noradrenergic nerve terminals) significantly attenuated the increase of α(1A)-adrenoceptor mRNA induced by a 14-day treatment with imipramine (IMI, 20 mg/kg, ip) and abolished the effect of electroconvulsive shock (ECS, 150 mA, 0.5 s) in the prefrontal cortex of the rat brain. The changes in the receptor protein expression (as reflected by its density) that were induced by IMI and ECS treatments were differently modulated by DSP-4 lesioning, and only the ECS-induced increase in α(1A)-adrenoceptor level was abolished. This study provides further evidence corroborating our initial hypothesis that the noradrenergic component of the action of antidepressant agents plays an essential role in the modulation of α(1A)-adrenoceptor in the rat cerebral cortex.
我们之前曾报道，慢性丙咪嗪和电休克治疗可增加大鼠大脑皮质中的α(1A)-肾上腺素能受体（但不是α(1B)亚型）mRNA 水平和受体密度。此外，我们还发现，西酞普兰的慢性治疗不会影响α(1A)-或α(1B)-肾上腺素能受体的表达，这表明之前观察到的α(1A)-肾上腺素能受体的上调可能取决于这些抗抑郁药作用机制的去甲肾上腺素成分。在这里，我们报告说，先前用 DSP-4（50mg/kg）（一种选择性作用于去甲肾上腺素能神经末梢的神经毒素）进行的去甲肾上腺素耗竭显著减弱了 14 天丙咪嗪（IMI，20mg/kg，ip）治疗引起的α(1A)-肾上腺素能受体 mRNA 增加，并消除了电休克（ECS，150mA，0.5s）在大鼠大脑前额叶的作用。由 IMI 和 ECS 处理诱导的受体蛋白表达（反映为其密度）的变化被 DSP-4 损伤以不同的方式调节，只有 ECS 诱导的α(1A)-肾上腺素能受体水平增加被消除。这项研究提供了进一步的证据，证实了我们的初始假设，即抗抑郁药作用的去甲肾上腺素成分在调节大鼠大脑皮质中的α(1A)-肾上腺素能受体中起着至关重要的作用。
