Elsevier

Neuroscience

Volume 144, Issue 1, 5 January 2007, Pages 1-7
Neuroscience

Rapid report
Darbepoetin alfa (Aranesp®) improves recognition memory in adult rats that have sustained bilateral ventral hippocampal lesions as neonates or young adults

https://doi.org/10.1016/j.neuroscience.2006.09.041Get rights and content

Abstract

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.

Section snippets

Animals and experimental protocols

All procedures were approved by the University Committee on Laboratory Animals and were conducted in accordance with Canadian Council on Animal Care guidelines. All efforts were made to minimize the number of animals used in this study, and every effort was taken to reduce any suffering. On postnatal day 7 (PD7) a group of Long-Evans rats (Charles River, Montreal, PQ, Canada) underwent either bilateral sham surgeries or lesions of the VH as described previously (Powell et al., 2006). On PD21,

Verification of the lesion

Lesions were restricted to the ventral portion of the hippocampus [Fig. 1 indicates the area of the hippocampus damaged by the lesion; adapted from the atlas of Paxinos and Watson (2005)]. Representative Cresyl Violet–stained sections from adult animals that received bilateral VH lesions as either neonates or young-adults are shown in Fig. 2, Fig. 3. Injection of ibotenic acid into the VH of neonatal and young-adult rats produced lesions of comparable size (Fig. 2B and 2D). No obvious damage

Discussion

The goals of this study were to assess NORT performance of adult animals that were VH lesioned either as neonates (PD7) or young adults (PD42), and to determine the effects of darbepoetin alfa on the NORT performance of these animals. We show here that adult nVH animals displayed deficits in recognition memory at delays of 0.5 and 2 h between the choice and sample phases in the NORT. This result is consistent with studies demonstrating working memory deficits in adult rats that have sustained

Acknowledgments

The authors would like to thank Amgen (Thousand Oaks, CA, USA) for supplying Aranesp®. This work was supported in part by a grant from CIHR (MOP-67017).

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