Inhibitory effect of neuropeptide Y on morphine withdrawal is accompanied by reduced c-fos expression in specific brain regions

Neuropeptide Y (NPY) was previously shown in our laboratory to attenuate be havioral signs of morphine withdrawal. To further characterize the anti-wit hdrawal effect of NPY, the present study attempted to identify specific bra in regions where NPY inhibits neuronal activity during withdrawal. Morphine dependence was induced in male Wistar rats by two daily subcutaneous injec tions of morphine at increasing doses, and the withdrawal syndrome was prec ipitated acutely by intraperitoneal administration of naloxone. Rats were p re-treated with an intracerebroventricular (icv) injection of NPY (12 nmol) or vehicle 30 min before the naloxone challenge. Withdrawal behavior was q uantified using a point scoring technique based on motor- and non-motor-rel ated signs. Brain areas involved in the attenuation of morphine withdrawal were delineated by radioactive in situ hybridization for the immediate earl y gene c-fos, which is a marker for neuronal activity. The present study co nfirmed the inhibitory effect of NPY on withdrawal behavior. Inhibition of behavioral signs of naloxone-precipitated morphine withdrawal was accompani ed by significantly reduced c-fos expression in the locus coeruleus, latera l septal nucleus, ventral part of the periaqueductal grey, cingulate and fr ontal cortices, and septohippocampal nucleus. Our data suggest that neo- an d allo-cortical areas as well as specific brainstem nuclei are involved in the anti-withdrawal effects of NPY. (C) 2001 Wiley-Liss, Inc.