Acute ketamine challenge increases resting state prefrontal-hippocampal connectivity in both humans and rats

• Verfasst von: Grimm, Oliver [VerfasserIn]
• Verfasst von: Sartorius, Alexander [VerfasserIn]
• Verfasst von: Meyer-Lindenberg, Andreas [VerfasserIn]
• Titel: Acute ketamine challenge increases resting state prefrontal-hippocampal connectivity in both humans and rats
• Verf.angabe: Oliver Grimm, Natalia Gass, Wolfgang Weber-Fahr, Alexander Sartorius, Esther Schenker, Michael Spedding, Celine Risterucci, Janina Isabel Schweiger, Andreas Böhringer, Zhenxiang Zang, Heike Tost, Adam James Schwarz, Andreas Meyer-Lindenberg
• E-Jahr: 2015
• Jahr: 18 July 2015
• Umfang: 11 S.
• Fussnoten: Gesehen am 20.12.2017
• Titel Quelle: Enthalten in: Psychopharmacology
• Ort Quelle: Berlin : Springer, 1959
• Jahr Quelle: 2015
• Band/Heft Quelle: 232(2015), 21-22, Seite 4231-4241
• ISSN Quelle: 1432-2072
• DOI: doi:10.1007/s00213-015-4022-y
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1566573017

Abstract

RationaleAberrant prefrontal-hippocampal (PFC-HC) connectivity is disrupted in several psychiatric and at-risk conditions. Advances in rodent functional imaging have opened the possibility that this phenotype could serve as a translational imaging marker for psychiatric research. Recent evidence from functional magnetic resonance imaging (fMRI) studies has indicated an increase in PFC-HC coupling during working-memory tasks in both schizophrenic patients and at-risk populations, in contrast to a decrease in resting-state PFC-HC connectivity. Acute ketamine challenge is widely used in both humans and rats as a pharmacological model to study the mechanisms of N-methyl-d-aspartate (NMDA) receptor hypofunction in the context of psychiatric disorders.ObjectivesWe aimed to establish whether acute ketamine challenge has consistent effects in rats and humans by investigating resting-state fMRI PFC-HC connectivity and thus to corroborate its potential utility as a translational probe.MethodsTwenty-four healthy human subjects (12 females, mean age 25 years) received intravenous doses of either saline (placebo) or ketamine (0.5 mg/kg body weight). Eighteen Sprague-Dawley male rats received either saline or ketamine (25 mg/kg). Resting-state fMRI measurements took place after injections, and the data were analyzed for PFC-HC functional connectivity.ResultsIn both species, ketamine induced a robust increase in PFC-HC coupling, in contrast to findings in chronic schizophrenia.ConclusionsThis translational comparison demonstrates a cross-species consistency in pharmacological effect and elucidates ketamine-induced alterations in PFC-HC coupling, a phenotype often disrupted in pathological conditions, which may give clue to understanding of psychiatric disorders and their onset, and help in the development of new treatments.