Intranasal administration of NAP, a neuroprotective peptide, decreases anxiety-like behavior in aging mice in the elevated plus maze.
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.
Alcalay
Roy N
RN
Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Giladi
Eliezer
E
Pick
Chaim G
CG
Gozes
Illana
I
D000281:Administration, Intranasal; D000367:Age Factors; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004334:Drug Administration Schedule; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008568:Memory / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D016896:Treatment Outcome
D014151:Anti-Anxiety Agents; D018696:Neuroprotective Agents; D009842:Oligopeptides; C425904:davunetide