Intranasal administration of NAP, a neuroprotective peptide, decreases anxiety-like behavior in aging mice in the elevated plus maze

Neurosci Lett. 2004 May 6;361(1-3):128-31. doi: 10.1016/j.neulet.2003.12.005.


NAP, an 8-amino-acid peptide (NAPVSIPQ=Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln), provides neuroprotection at very low doses in a variety of animal models. Previously, acute NAP administration by the intranasal route resulted in improved performance in the Morris water maze of normal and cognitively impaired rats. In these animals, it was observed, but not quantified, that NAP exhibited an anxiolytic effect. Therefore, we have tested here the effects of chronic NAP treatment on anxiety-like behavior in mice in the elevated plus maze. Results showed that 5 months of daily (intranasal) treatment with NAP reduced anxiety, measured as the percentage of time spent in the open arms of the maze (P < 0.01). This effect was maintained after a longer (8 months) exposure to NAP. In addition, after 8 months of NAP treatment, the percentage of open arm entries out of total arms entries was significantly higher in the treated mice ( P < 0.01). Motor function indices indicated no significant differences between the groups. Furthermore, prolonged treatment with NAP (7 months) showed some beneficial effects on Morris water maze performance in the aging mice. It is concluded that NAP offers a unique combination of anxiolytic/cognitive enhancing properties observed after prolonged chronic intranasal treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Age Factors
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / physiopathology
  • Anxiety Disorders / psychology
  • Drug Administration Schedule
  • Male
  • Maze Learning / drug effects*
  • Maze Learning / physiology
  • Memory / drug effects
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Oligopeptides / pharmacology*
  • Treatment Outcome


  • Anti-Anxiety Agents
  • Neuroprotective Agents
  • Oligopeptides
  • davunetide