Neuropeptide S inhibits the acquisition and the expression of conditioned place preference to morphine in mice

Peptides. 2009 Feb;30(2):234-40. doi: 10.1016/j.peptides.2008.10.004. Epub 2008 Oct 17.


Neuropeptide S (NPS), a recently identified bioactive peptide, was reported to regulate arousal, anxiety, motoring and feeding behaviors. NPS precursor and NPS receptor mRNA were found in the amygdala, the ventral tegmental area (VTA) and the substantia nigra, the area thought to modulate rewarding properties of drugs. In the present study, we examined the influence of NPS on the rewarding action of morphine, using the unbiased conditioned place preference (CPP) paradigm. Morphine (1, 3 and 6 nmol, i.c.v.) induced a significant place preference. For testing the effect of NPS on the acquisition of morphine CPP, mice were given the combination of NPS and morphine on the conditioning days, and without drug treatment on the followed test day. To study the effect of NPS on the expression of morphine CPP, mice received the treatment of saline/morphine on the conditioning days, and NPS on the test day, 15 min before the placement in the CPP apparatus. Our results showed that NPS (0.3-10 nmol) alone neither induced place preference nor aversion, however, NPS (1 and 3 nmol) blocked the acquisition of CPP induced by 3 nmol morphine, and acquisition of 6 nmol morphine-induced CPP was also reduced by NPS (6 and 10 nmol). Moreover, the expression of CPP induced by 6 nmol morphine was also inhibited by NPS (0.1, 1 and 10 nmol). These results revealed the involvement of NPS in rewarding activities of morphine, and demonstrated the interaction between NPS system and opioid system for the first time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Conditioning, Psychological / drug effects*
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred Strains
  • Morphine / pharmacology*
  • Neuropeptides / administration & dosage
  • Neuropeptides / pharmacology*


  • Neuropeptides
  • neuropeptide S, mouse
  • Morphine