Clausen T R, Møller M, Woldbye D P
Laboratory of Neuropsychiatry, Department of Pharmacology, University of Copenhagen, Copenhagen, Denmark.
J Neurosci Res. 2001 May 15;64(4):410-7. doi: 10.1002/jnr.1092.
Neuropeptide Y (NPY) was previously shown in our laboratory to attenuate behavioral signs of morphine withdrawal. To further characterize the anti-withdrawal effect of NPY, the present study attempted to identify specific brain regions where NPY inhibits neuronal activity during withdrawal. Morphine dependence was induced in male Wistar rats by two daily subcutaneous injections of morphine at increasing doses, and the withdrawal syndrome was precipitated acutely by intraperitoneal administration of naloxone. Rats were pre-treated with an intracerebroventricular (icv) injection of NPY (12 nmol) or vehicle 30 min before the naloxone challenge. Withdrawal behavior was quantified using a point scoring technique based on motor- and non-motor-related signs. Brain areas involved in the attenuation of morphine withdrawal were delineated by radioactive in situ hybridization for the immediate early gene c-fos, which is a marker for neuronal activity. The present study confirmed the inhibitory effect of NPY on withdrawal behavior. Inhibition of behavioral signs of naloxone-precipitated morphine withdrawal was accompanied by significantly reduced c-fos expression in the locus coeruleus, lateral septal nucleus, ventral part of the periaqueductal grey, cingulate and frontal cortices, and septohippocampal nucleus. Our data suggest that neo- and allo-cortical areas as well as specific brainstem nuclei are involved in the anti-withdrawal effects of NPY.
本实验室先前的研究表明，神经肽Y（NPY）可减轻吗啡戒断的行为症状。为了进一步明确NPY的抗戒断作用，本研究试图确定在戒断期间NPY抑制神经元活动的特定脑区。通过每日两次皮下注射递增剂量的吗啡，诱导雄性Wistar大鼠产生吗啡依赖性，然后腹腔注射纳洛酮急性诱发戒断综合征。在纳洛酮激发前30分钟，给大鼠脑室内注射NPY（12 nmol）或溶剂进行预处理。使用基于运动和非运动相关症状的评分技术对戒断行为进行量化。通过对即早基因c-fos进行放射性原位杂交来描绘参与减轻吗啡戒断的脑区，c-fos是神经元活动的标志物。本研究证实了NPY对戒断行为的抑制作用。NPY对纳洛酮诱发的吗啡戒断行为症状的抑制作用伴随着蓝斑、外侧隔核、导水管周围灰质腹侧、扣带回和额叶皮质以及隔海马核中c-fos表达的显著降低。我们的数据表明，新皮质和旧皮质区域以及特定的脑干核团参与了NPY的抗戒断作用。
