Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats.
The FGL peptide is a neural cell adhesion molecule-derived fibroblast growth factor receptor agonist. FGL has both neurotrophic and memory enhancing properties. Neonatal phencyclidine (PCP) treatment on postnatal days 7, 9, and 11 has been shown to result in long-lasting behavioral abnormalities, including cognitive impairment relevant to schizophrenia. The present study investigated the effect of FGL on spatial learning and memory deficits induced by neonatal PCP treatment. Rat pups were treated with 30 mg/kg PCP on postnatal days 7, 9, and 11. Additionally, the rats were subjected to a chronic FGL treatment regimen where FGL was administered throughout development. Rats were tested as adults for spatial reference memory, reversal learning, and working memory in the Morris water maze. The PCP-treated rats demonstrated a robust impairment in working memory and reversal learning. However, the long-term memory component of the reference memory task was not affected by PCP. Chronic FGL treatment had no effect on the reversal learning impairment but ameliorated the working memory deficits almost to the levels of the control groups. In conclusion, the results suggest that the neonatal PCP treatment produced deficits in cognition relevant to schizophrenia. Moreover, working memory function was selectively protected by the neurotrophic peptide, FGL.
Secher
Thomas
T
Protein Laboratory, Institute of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. tsecher@sund.ku.dk
Berezin
Vladimir
V
Bock
Elisabeth
E
Glenthøj
Birte
B
D000818:Animals; D000831:Animals, Newborn / Q000523:psychology*; D005260:Female; D008297:Male; D008568:Memory / Q000187:drug effects*; D019006:Neural Cell Adhesion Molecules / Q000008:administration & dosage / Q000819:agonists* / Q000494:pharmacology; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012193:Reversal Learning / Q000187:drug effects
C488618:NCAM protein (681-695), human; D019006:Neural Cell Adhesion Molecules; D010622:Phencyclidine