Brief reportsTransient N-methyl-D-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to schizophrenia
Section snippets
Subjects and treatment schedule
Male Sprague-Dawley rats (n = 44) from 14 litters born to different dams (Harlan, Somerville, New Jersey) were used. On postnatal day 6 (P6), pups were randomly assigned to one of two treatment groups: vehicle (saline, 1 mL/kg) or MK801 (.1 mg/kg per injection). The pups were weighed daily from P6 through P11 and weekly thereafter.
Beginning on P7, pups received subcutaneous injections twice daily (09:00 and 16:00) for 4 days. Pups were removed from their dam for 1 hour for the injection, during
Results
MK801-treated pups gained significantly less weight during the treatment period than did their vehicle-treated counterparts (Table 1). However, by P60, there were no significant treatment-dependent differences.
Discussion
Transient inhibition of NMDA receptors during a period critical to frontal cortical development significantly impaired cognitive set-shifting abilities and working memory in adult rats without affecting long-term recognition memory or motor behavior. These results suggest that reducing NMDA receptor function during a critical period of development can produce selective cognitive deficits relevant to those reported in patients with schizophrenia and individuals who are susceptible to develop
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