Dolzhenko A T, Komissarov I V
Biull Eksp Biol Med. 1986 May;101(5):569-70.
The experiments on rats have shown that antidepressant concentrations that cause 50% inhibition of 14C-NA and 3H-HT uptake by brain slices remain unchanged following prolonged administration of antidepressants (imipramine, pirazidole, harmane and its derivatives--C-153, C-307, C-394, C-395), as compared to the control. Electrical stimulation of brain slices upon long-term treatment of rats with antidepressants and preincubation with 14C-NA and 3H-HT enhanced presynaptic release of radioactive mark at concentrations of antidepressants (EC2) 3-14 times lower than those in the control animals. Long-term antidepressant administration reduces the inhibitory influence of clonidine and HT on presynaptic release of 14C-NA and 3H-HT by brain slices. It is suggested that long-term administration of antidepressants decreases the sensitivity of terminal axons of NA- and HT-ergic neurons to autoinhibitory effect of neurotransmitter release.
对大鼠的实验表明,与对照组相比,长期给予抗抑郁药(丙咪嗪、匹拉唑、哈尔满及其衍生物——C - 153、C - 307、C - 394、C - 395)后,导致脑片对14C - 去甲肾上腺素(NA)和3H - 5 - 羟色胺(HT)摄取抑制50%的抗抑郁药浓度保持不变。在用抗抑郁药长期治疗大鼠并使其与14C - NA和3H - HT预孵育后,对脑片进行电刺激,结果显示在抗抑郁药浓度(EC2)比对照动物低3 - 14倍时,放射性标记的突触前释放增强。长期给予抗抑郁药可降低可乐定和5 - 羟色胺对脑片14C - NA和3H - HT突触前释放的抑制作用。有人提出,长期给予抗抑郁药会降低去甲肾上腺素能和5 - 羟色胺能神经元终末轴突对神经递质释放自身抑制作用的敏感性。