Pavković Željko, Smiljanić Kosara, Kanazir Selma, Milanović Desanka, Pešić Vesna, Ruždijić Sabera
Department of Neurobiology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
Paediatr Anaesth. 2017 Sep;27(9):962-972. doi: 10.1111/pan.13182.
Propofol is commonly used in modern anesthesiology. Some findings suggest that it is highly addictive.
In this study it was examined whether propofol anesthesia exposure was able to induce behavioral alterations and brain molecular changes already described in addictive drug usage in peripubertal rats, during the onset of mid/periadolescence as a developmental period with increasing vulnerability to drug addiction.
The expression of D1 dopamine receptor, a dopamine, and cAMP-regulated phosphoprotein with a Mr 32 000; Ca /calmodulin-dependent protein kinase IIα; and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B was examined in peripubertal rats 4, 24, and 48 hour after propofol anesthesia exposure by Western blot and immunohistochemistry. Brain regions of interest were the medial prefrontal cortex, the striatum, and the thalamus. Anxiety and behavioral cross-sensitization to d-amphetamine were examined as well.
Significant increase in the expression of dopamine and cAMP-regulated phosphoprotein with a Mr 32 000 phosphorylated at threonine 34, a postsynaptic marker of dopaminergic neurotransmission, and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B, a marker of neuronal activity, was detected in the thalamus of experimental animals 4-24 hour after the treatment, with the accent on the paraventricular thalamic nucleus. Significant increase in the expression of Ca /calmodulin-dependent protein kinase IIα phosphorylated at threonine 286, a sensor of synaptic activity, was observed in the prefrontal cortex and the striatum 24 hour after propofol anesthesia exposure. It was accompanied by a significant decrease in Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B expression in the striatum. Decreased behavioral inhibition in aversive environment and increased motor response to d-amphetamine in a context-independent manner were observed as well.
In peripubertal rats, propofol anesthesia exposure induces transient molecular and behavioral response that share similarities with those reported previously for addictive drugs. In the absence of additional pharmacological manipulation, all detected effects receded within 48 hour after the treatment.
丙泊酚在现代麻醉学中被广泛使用。一些研究结果表明它具有高度成瘾性。
本研究旨在探讨在青春期中期/青春期前后这一药物成瘾易感性增加的发育阶段，丙泊酚麻醉暴露是否会在青春期前大鼠中诱发已在成瘾药物使用中描述的行为改变和脑部分子变化。
通过蛋白质免疫印迹法和免疫组织化学法检测青春期前大鼠在丙泊酚麻醉暴露后4小时、24小时和48小时时多巴胺D1受体、一种多巴胺和cAMP调节的32kDa磷蛋白、钙/钙调蛋白依赖性蛋白激酶IIα以及Finkel-Biskis-Jinkins小鼠骨肉瘤病毒癌基因同源物B的表达。感兴趣的脑区为内侧前额叶皮质、纹状体和丘脑。还检测了焦虑和对右旋苯丙胺的行为交叉致敏性。
在治疗后4至24小时，实验动物丘脑内检测到多巴胺和cAMP调节的32kDa磷蛋白（多巴胺能神经传递的突触后标志物，在苏氨酸34处磷酸化）以及神经元活动标志物Finkel-Biskis-Jinkins小鼠骨肉瘤病毒癌基因同源物B的表达显著增加，以室旁丘脑核最为明显。丙泊酚麻醉暴露24小时后，前额叶皮质和纹状体内在苏氨酸286处磷酸化的钙/钙调蛋白依赖性蛋白激酶IIα（突触活动传感器）表达显著增加。同时纹状体内Finkel-Biskis-Jinkins小鼠骨肉瘤病毒癌基因同源物B的表达显著降低。还观察到在厌恶环境中行为抑制能力下降以及对右旋苯丙胺的运动反应以与环境无关的方式增加。
在青春期前大鼠中，丙泊酚麻醉暴露会诱发短暂的分子和行为反应，这些反应与先前报道的成瘾药物的反应相似。在没有额外药物干预的情况下，所有检测到的效应在治疗后48小时内消退。
