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.