Darbepoetin alfa (Aranesp) improves recognition memory in adult rats that have sustained bilateral ventral hippocampal lesions as neonates or young adults.
Recognition memory was assessed in adult rats that received bilateral injections of saline (sham lesions) or ibotenic acid (lesioned) in the ventral hippocampus as neonates (postnatal day 7, PD7) or young adult (42 days of age, PD42) using the Novel Object Recognition Test (NORT). Normal or sham-lesioned rats were able to distinguish novel from familiar objects over a 0.5 and 2 h delay between the sample and choice phases. Adult rats (PD70) lesioned as neonates performed progressively worse than sham-lesioned animals at delays of 0.5 and 2 h. A single injection of darbepoetin alfa (500 or 5000 U/kg, i.p.), given 1 h before the sample phase restored performance 0.5 or 2 h later in the choice phase to same levels as sham-lesioned rats. Adults lesioned on PD42 displayed deficits in NORT performance with a 2 h delay between the choice and sample phases that were completely reversed by administration of darbepoetin alfa (5000 U/kg, i.p.) 1 h before the sample phase. These results suggest that darbepoetin alfa may have utility in treating memory deficits associated with brain dysfunction related to developmental disorders such as schizophrenia.
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Department of Pharmacology, Sir Charles Tupper Medical Building, Faculty of Medicine, Dalhousie University, 5850 College Street, Halifax, Nova Scotia, Canada B3H 1X5.
Powell
K J
KJ
Robertson
G S
GS
D000818:Animals; D000831:Animals, Newborn; D003216:Conditioning, Operant / Q000187:drug effects; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006624:Hippocampus / Q000473:pathology*; D007274:Injections, Intraperitoneal; D008568:Memory / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D021641:Recognition, Psychology / Q000187:drug effects*
D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa