Tr. Clausen et al., Inhibitory effect of neuropeptide Y on morphine withdrawal is accompanied by reduced c-fos expression in specific brain regions, J NEUROSC R, 64(4), 2001, pp. 410-417
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.