The NMDA receptor plays a role in mental processes ranging from mood regulation to memory formation. Ketamine, a non-selective NMDA antagonist, has both rapid antidepressant effects and side effects similar to the symptomology of schizophrenia. Another link between these disorders is working memory, which relies on the NMDA receptor and specifically NR2B-subunit function. This experiment tested the effects of acute and long-term administration of ketamine and an NR2B-specific antagonist (traxoprodil) on working memory in rats. Rats were tested with a spatial working memory procedure on the eight-arm radial arm maze after acute and repeated doses of each drug. After the animals’ final day of testing on the maze, brains were extracted for immunohistochemistry staining using a c-fos antibody. The results showed a trend indicating that animals repeatedly administered ketamine perform better on working memory tasks than those administered saline or traxoprodil. The animals administered ketamine also showed significantly lower c-fos expression in areas of their frontal cortex compared to animals receiving saline or traxoprodil. These results indicate that the long-term effects of ketamine do not appear to be the result of its action on the NR2B subunit. These findings have positive implications for the therapeutic use of low doses of this drug class for depression and hints at dose-related differences in the effects of repeated ketamine administration.
Fleming, Leah, "The Impact of NMDA and NR2B-specific Antagonists on Working Memory Function and C-fos Expression in Rats: Unraveling the Ketamine Mystery" (2016). Behavioral Neuroscience Honors Papers. 6.
The views expressed in this paper are solely those of the author.