Przewłocki R, Lasoń W, Turchan J, Przewłocka B
Department of Molecular Neuropharmacology, Polish Academy of Sciences, Kraków, Poland.
Pol J Pharmacol. 1997 Sep-Oct;49(5):351-5.
Endogenous opioids have been implicated in the mechanism of action of antidepressant drugs. In this study, we evaluated effects of single and repeated imipramine administration on proenkephalin and prodynorphin gene expression in the rat nucleus accumbens and striatum. In situ hybridization study showed that single imipramine injection (10 mg/kg, i.p.) decreased the level of proenkephalin (by ca. 20%) and prodynorphin (by ca. 25%) mRNA to the same extent in both structures. Repeated imipramine administration (10 mg/kg i.p. twice daily for 10 days) had no effect on proenkephalin mRNA level, whereas the prodynorphin gene expression was regulated differently. At 3 h after the last dose of imipramine the prodynorphin mRNA level was decreased (by ca. 25%) in the striatum, but not in the nucleus accumbens, whereas at 24 h an up-regulation (by ca. 27%) of prodynorphin mRNA level could be observed in the nucleus accumbens only. In the light of involvement of opioids in mood regulation, these adaptive changes may participate in neurochemical mechanisms of antidepressant therapy.
内源性阿片肽与抗抑郁药物的作用机制有关。在本研究中，我们评估了单次和重复给予丙咪嗪对大鼠伏隔核和纹状体中前脑啡肽原和强啡肽原基因表达的影响。原位杂交研究表明，单次注射丙咪嗪（10mg/kg，腹腔注射）使这两个结构中的前脑啡肽原（约降低20%）和强啡肽原（约降低25%）mRNA水平降低到相同程度。重复给予丙咪嗪（10mg/kg腹腔注射，每日两次，共10天）对前脑啡肽原mRNA水平没有影响，而强啡肽原基因表达的调节则有所不同。在最后一剂丙咪嗪给药后3小时，纹状体中的强啡肽原mRNA水平降低（约25%），但伏隔核中未降低，而在24小时时，仅在伏隔核中观察到强啡肽原mRNA水平上调（约27%）。鉴于阿片肽参与情绪调节，这些适应性变化可能参与抗抑郁治疗的神经化学机制。
