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Author Notes:

Corresponding Author: Dr. Leonard Howell, Associate Director, Scientific Programs, Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd NE, Atlanta, GA 30329, Email:lhowell@emory.edu, Phone: (404) 727 7786, Fax: (404) 727 1266

The authors declare no competing financial interests.

Subjects:

Research Funding:

This research was supported by P51OD11132 (Yerkes National Primate Research Center), Sunovion Pharmaceutical, Ltd (LLH) and DA031246 (LLH). Special thanks to the Yerkes Imaging Center, technicians Marisa Olsen and Juliet Brown, and to Christopher Muly, MD, PhD.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Pharmacology & Pharmacy
  • Psychiatry
  • Neurosciences & Neurology
  • Ketamine
  • Schizophrenia
  • Nonhuman primates
  • Pharmacological MRI
  • Translational models
  • Antipsychotic drugs
  • TREATMENT-RESISTANT DEPRESSION
  • HEALTHY-VOLUNTEERS
  • RHESUS-MONKEYS
  • SCHIZOPHRENIA
  • HUMANS
  • NMDA
  • FMRI
  • CONNECTIVITY
  • STIMULATION
  • RISPERIDONE

Ketamine-induced brain activation in awake female nonhuman primates: a translational functional imaging model

Tools:

Journal Title:

Psychopharmacology

Volume:

Volume 233, Number 6

Publisher:

, Pages 961-972

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Rationale There is significant interest in the NMDA-receptor antagonist ketamine due to its efficacy in treating depressive disorders and its induction of psychotic-like symptoms that make it a useful tool for modeling psychosis. Objective The present study extends the successful development of an apparatus and methodology to conduct pharmacological MRI studies in awake rhesus monkeys in order to evaluate the CNS effects of ketamine. Methods Functional MRI scans were conducted in four awake adult female rhesus monkeys during sub-anesthetic i.v. infusions of ketamine (0.345 mg/kg bolus followed by 0.256 mg/kg/hr constant infusion) with and without risperidone pretreatment (0.06mg/kg). Statistical parametric maps of ketamine-induced BOLD activation were obtained with appropriate GLM models incorporating motion and hemodynamics of ketamine infusion. Results Ketamine infusion induced and sustained robust BOLD activation in a number of cortical and subcortical regions, including the thalamus, cingulate gyrus, and supplementary motor area. Pretreatment with the antipsychotic drug risperidone markedly blunted ketamine-induced activation in many brain areas. Conclusions The results are remarkably similar to human imaging studies showing ketamine-induced BOLD activation in many of the same brain areas, and pretreatment with risperidone or another antipsychotic blunting the ketamine response to a similar extent. The strong concordance of the functional imaging data in humans with these results from nonhuman primates highlights the translational value of the model and provides an excellent avenue for future research examining the CNS effects of ketamine. This model may also be a useful tool for evaluating the efficacy of novel antipsychotic drugs.

Copyright information:

© 2015 Springer-Verlag.

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