Neuropeptide S (NPS) is a newly identified
ligand for the previously discovered
G-protein coupled receptor 154 now named NPSR. Recently, it has been found that NPSR gene expression is altered during
ethanol withdrawal. In this study we tried to elucidate if NPSR gene expression is modified in response to
morphine withdrawal and its protracted abstinence. To induce
opioid dependence Wistar rats were treated for 7 days with
morphine. Twelve hours and 7 days after the last
morphine administration brains were removed and the expression of NPSR
mRNA was analyzed by in situ hybridization (ISH). Successful induction of
opioid dependence was confirmed by the
naloxone-precipitated withdrawal test 2 h after the last
morphine administration. Moreover, 7 days after the last
morphine dose animals were checked for signs of anxiety and for intracerebroventricular (ICV) NPS (0.3 and 1.0 nmol) induced
anxiolytic effects by elevated plus maze (EPM). Results showed that in
morphine treated rats strong somatic signs of
naloxone-precipitated withdrawal occurred. ISH data revealed changes in NPSR gene expression in the ventral tegmental area as well as in the basolateral amygdaloid and bed nucleus of stria terminalis at 12 h and 7 days into abstinence, respectively. At 7 days into abstinence post dependent animals showed higher levels of anxiety than controls which were significantly attenuated by NPS. These results demonstrated that
morphine dependence induction led to (i) changes in NPSR
mRNA expression; (ii) increased anxiety; and (iii) more potent
anxiolytic-like effect of NPS.