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Abstract #2305

Sub-Anesthetic Ketamine Modulates Intrinsic BOLD Connectivity in the Hippocampal-Prefrontal System in the Rat: Dose-Dependence and PK/PD Relationships

Natalia Gass1, Alexander Sartorius1, Adam James Schwarz2, 3, Esther Schenker4, Celine Risterucci5, Michael Spedding4, Lei Zheng1, Andreas Meyer-Lindenberg1, Wolfgang Weber-Fahr1

1Central Institute of Mental Health, Mannheim, Germany; 2Eli Lilly and Company, Indianapolis, IN, United States; 3Indiana University, Bloomington, IN, United States; 4Institut de Recherches Servier, Croissy-sur-Seine, France; 5F. Hoffmann-La Roche, Basel, Switzerland

The aim of this work was to systematically characterize the effects of ketamine, a rapidly acting antidepressant, on rsfMRI in rat. Male Sprague-Dawley rats in 4 parallel groups received either vehicle or one of three sub-anesthetic doses of S-ketamine. Three rsfMRI datasets were acquired from each rat: pre-injection and 15 and 30 min post-injection. Pharmacokinetic/pharmacodynamic image and region-of-interest analyses revealed increased functional connectivity between the hippocampus and regions in the prefrontal cortex, and within the prefrontal cortex, that positively correlated with ketamine plasma levels. The observed increases in functional connectivity reveal possible neural mechanisms underlying established behavioral effects of ketamine.