Heberlein Annemarie, Bleich Stefan, Kornhuber Johannes, Hillemacher Thomas
Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Germany.
Hum Psychopharmacol. 2008 Apr;23(3):171-81. doi: 10.1002/hup.911.
Benzodiazepines are known to modulate the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis by antagonizing the effects of corticotropin-releasing factor (CRH). Besides regulating the HPA axis CRH evolves properties of a neurotransmitter in the limbic system that is closely involved in the delivery of the emotional consequences of the stress response. At a superordinated level Neuropeptide Y (NPY) and Cholecystokinin (CCK) affect the release of CRH and modulate thereby the intensity of the physiological stress response. Benzodiazepine treatment interferes not only with the release of CRH but also with the release of NPY and CCK. Alterations in the intracortical ratio of NPY, CCK and CRH are correlated with behavioural changes like increased respectively decreased anxiety and subsequent alterations in the activity of the HPA axis. Recent research offers the possibility that the alterations of plasma levels of these neuropeptides are not only a secondary phenomenon due to drug intake, but that low levels of those neuropeptides that modulate anxiety and fear can possibly explain addiction to substances that counterbalance these deficits. Depending on the available results possible implications of NPY and CCK on benzodiazepine addiction and withdrawal symptoms are reviewed, thereby providing topics for further research.
已知苯二氮䓬类药物可通过拮抗促肾上腺皮质激素释放因子（CRH）的作用来调节下丘脑 - 垂体 - 肾上腺皮质（HPA）轴的活性。除了调节HPA轴外，CRH还具有边缘系统中神经递质的特性，该系统与应激反应的情绪后果传递密切相关。在更高层次上，神经肽Y（NPY）和胆囊收缩素（CCK）影响CRH的释放，从而调节生理应激反应的强度。苯二氮䓬类药物治疗不仅会干扰CRH的释放，还会干扰NPY和CCK的释放。NPY、CCK和CRH的皮质内比例变化与行为改变相关，如焦虑增加或减少，以及随后HPA轴活性的改变。最近的研究表明，这些神经肽血浆水平的变化不仅可能是药物摄入引起的次要现象，而且调节焦虑和恐惧的神经肽水平较低可能解释了对平衡这些缺陷的物质的成瘾。根据现有结果，综述了NPY和CCK对苯二氮䓬类药物成瘾和戒断症状的可能影响，从而为进一步研究提供了课题。
