Abstract
Subanesthetic doses of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine exacerbate psychosis in schizophrenic patients, and ketamine has significant abuse liability. These observations indicate that a secondary effect of ketamine may be to increase dopamine concentrations. The present study was undertaken using positron emission tomography (PET) and the dopamine (D2) radiotracer 11C-raclopride to determine whether ketamine would decrease D2 receptor availability, indicative of an increase in dopamine concentrations. Two scans were performed in seven male control subjects before and after administration of ketamine (0.5 mg/kg, IV infused over 20 min). Ketamine significantly increased cortisol levels and decreased dopamine receptor availability in the striatum (specific binding), but not in the cerebellum (nonspecific binding). In addition, the cerebellar binding subtracted from the striatal binding (to account for changes in nonspecific binding) was significantly decreased after ketamine administration. These results provide in vivo evidence for the ability of ketamine to increase striatal dopamine concentrations, consistent with the role of the NMDA receptor in modulating dopamine function.
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Acknowledgements
This study was supported in part by Department of Energy/Office of Environmental Research; Grants NS15638 and NS15380 from National Institute of Neurological Disorders and Stroke; Grants MH49936, MH47277 and MH49165 from the National Institute for Mental Health; Grant RR-00096 from the National Center for Research Resources; Young Investigator Awards (to GSS and PS) and Established Investigator Awards (to SLD and JDB) from the National Alliance for Research in Schizophrenia and Depression (NARSAD) and a grant from the Whitehead Foundation (to GSS). The following individuals are gratefully acknowledged for their contribution to the studies: Noelwah Netusil and Theodore Johnson for patient care, Donald Warner and Naomi Pappas for PET operations, Colleen Shea, Thomas P. Martin, and Darren Jenkins for radiopharmaceutical preparation, and Clarence Barrett and Robert Carciello for cyclotron operations.
This manuscript is dedicated to the memory of Dr. Elsa J. Bartlett.
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Smith, G., Schloesser, R., Brodie, J. et al. Glutamate Modulation of Dopamine Measured in Vivo with Positron Emission Tomography (PET) and 11C-Raclopride in Normal Human Subjects. Neuropsychopharmacol 18, 18–25 (1998). https://doi.org/10.1016/S0893-133X(97)00092-4
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DOI: https://doi.org/10.1016/S0893-133X(97)00092-4
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