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Abstract #0365

Comparison of the Central Effects of Ketamine and the NR2B-Selective NMDA Receptor Antagonist Traxoprodil Using Pharmacological MRI in Conscious Rats

Haiying Tang 1 , Yu-Wen Li 1 , Matthew Fronheiser 1 , Daniel Kukral 1 , Harold Malone 1 , Adrienne Pena 1 , Gabriel Tobon 2 , Kurex Sidik 1 , Patrick Chow 1 , Linda Bristow 1 , Wendy Hayes 1 , and Feng Luo 1

1 Bristol-Myers Squibb, Princeton, NJ, United States, 2 InviCRO, Boston, MA, United States

Major depressive disorder (MDD), a leading cause of disability globally, has an enormous social and economic impact. Improvements in the efficacy of antidepressant therapy are needed. Ketamine is a nonselective NMDA antagonist which has been reported to have antidepresseant effects in patients with MDD. Significant efforts have been reported in the development of NR2B subtype-selective antagonists, to minimize adverse side effects observed with nonselective NMDA antagonists. In the present study we implemented pharmacological MRI (phMRI) in conscious rats to map the central effects of ketamine and traxoprodil, and to study the neurocircuitry that might attribute to the antidepressant effects.

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