TY - JOUR
T1 - Intranasal administration of NAP, a neuroprotective peptide, decreases anxiety-like behavior in aging mice in the elevated plus maze
AU - Alcalay, Roy N.
AU - Giladi, Eliezer
AU - Pick, Chaim G.
AU - Gozes, Illana
N1 - Funding Information:
This work is in partial fulfillment of the MD thesis requirements for Dr Roy N. Alcalay. We thank Dr Avi Spier for critical reading of the manuscript. Professor Illana Gozes is the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors. This study was supported, in part, by the Institute for the Study of Aging and Allon Therapeutics Inc., USA, and the Israel Science Foundation.
PY - 2004/5/6
Y1 - 2004/5/6
N2 - 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.
AB - 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.
KW - Aging
KW - Anxiety
KW - Intranasal
KW - Neuroprotection
KW - Rodent
KW - Vasoactive intestinal peptide
UR - http://www.scopus.com/inward/record.url?scp=2342561068&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2003.12.005
DO - 10.1016/j.neulet.2003.12.005
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C2 - 15135910
AN - SCOPUS:2342561068
SN - 0304-3940
VL - 361
SP - 128
EP - 131
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1-3
ER -