Maione S, Palazzo E, Pallotta M, Leyva J, Berrino L, Rossi F
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, 2nd University of Naples, Italy.
Psychopharmacology (Berl). 1997 Dec;134(4):401-5. doi: 10.1007/s002130050477.
The effect of acute administrations of three doses of imipramine (1, 5 and 10 mg/kg s.c.), a widely used tricyclic antidepressant, on extracellular levels of serotonin (5-HT) has been studied by intracerebral microdialysis in raphe nuclei and prefrontal cortex of conscious rats. Imipramine 1 mg/kg s.c. did not change extracellular 5-HT in either raphe nuclei and prefrontal cortex. However, with the dose of 5 mg/kg s.c. imipramine induced in raphe nuclei, a brief increase of extracellular 5-HT followed by a lowering (55-65% basal release) of the neurotransmitter. The same dose of imipramine decreased (60-70% of basal value) extracellular 5-HT in prefrontal cortex. Imipramine 10 mg/kg s.c. significantly increased 5-HT levels in both raphe nuclei (190 +/- 20% above basal value) and prefrontal cortex (280 +/- 15% above basal value). Pretreatment with (-)pindolol (5 mg/kg s.c.), a non-selective 5-HT1A subtype receptor antagonist, 30 min before imipramine 5 mg/kg, modified the effect of the antidepressant: an increase, instead of a decrease, on prefrontal cortex dialysate 5-HT was observed. (-)Pindolol (10 mg/kg s.c.) increased extracellular 5-HT in both raphe nuclei (155 +/- 20% above basal value) and prefrontal cortex (160 +/- 8% above basal value). These data show that acute administration of imipramine modifies extracellular 5-HT at the level of the raphe nuclei and prefrontal cortex. 5-HT1A autoreceptors in the raphe nuclei, which this study suggests to be tonically active, may be stimulated after systemic administration of high doses of imipramine.
通过脑内微透析技术，在清醒大鼠的中缝核和前额叶皮质中，研究了三种剂量（1、5和10毫克/千克，皮下注射）的丙咪嗪（一种广泛使用的三环类抗抑郁药）急性给药对细胞外5-羟色胺（5-HT）水平的影响。皮下注射1毫克/千克的丙咪嗪对中缝核和前额叶皮质的细胞外5-HT均无影响。然而，皮下注射5毫克/千克的丙咪嗪可使中缝核中的细胞外5-HT短暂升高，随后神经递质水平降低（降至基础释放量的55 - 65%）。相同剂量的丙咪嗪可使前额叶皮质中的细胞外5-HT降低（降至基础值的60 - 70%）。皮下注射10毫克/千克的丙咪嗪可使中缝核（比基础值高190±20%）和前额叶皮质（比基础值高280±15%）中的5-HT水平显著升高。在注射5毫克/千克丙咪嗪前30分钟，用非选择性5-HT1A亚型受体拮抗剂（-）吲哚洛尔（5毫克/千克，皮下注射）进行预处理，可改变抗抑郁药的作用：观察到前额叶皮质透析液中的5-HT出现升高而非降低。（-）吲哚洛尔（10毫克/千克，皮下注射）可使中缝核（比基础值高155±20%）和前额叶皮质（比基础值高160±8%）中的细胞外5-HT升高。这些数据表明，丙咪嗪急性给药可改变中缝核和前额叶皮质水平的细胞外5-HT。本研究表明中缝核中的5-HT1A自身受体具有紧张性活性，在全身给予高剂量丙咪嗪后可能会被激活。
