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- Title
Acute ketamine challenge increases resting state prefrontal-hippocampal connectivity in both humans and rats.
- Authors
Grimm, Oliver; Gass, Natalia; Weber-Fahr, Wolfgang; Sartorius, Alexander; Schenker, Esther; Spedding, Michael; Risterucci, Celine; Schweiger, Janina; Böhringer, Andreas; Zang, Zhenxiang; Tost, Heike; Schwarz, Adam; Meyer-Lindenberg, Andreas
- Abstract
Rationale: Aberrant 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. Objectives: We 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. Methods: Twenty-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. Results: In both species, ketamine induced a robust increase in PFC-HC coupling, in contrast to findings in chronic schizophrenia. Conclusions: This 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.
- Subjects
HIPPOCAMPUS physiology; NEURAL circuitry; KETAMINE; FUNCTIONAL magnetic resonance imaging; MENTAL illness; LABORATORY rats
- Publication
Psychopharmacology, 2015, Vol 232, Issue 21/22, p4231
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-015-4022-y