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¹H-[¹³C]-nuclear magnetic resonance spectroscopy measures of ketamine's effect on amino acid neurotransmitter metabolism.

ABSTRACT: Ketamine has recently gained significant attention owing to its psychotomimetic and more recently discovered rapid antidepressant-like properties. ¹H-[¹³C]-nuclear magnetic resonance studies were employed to explore potential physiological processes underlying these unique effects. [1-¹³C]glucose and [2-¹³C]acetate-nuclear magnetic resonance ex vivo studies were performed on the medial prefrontal cortex (mPFC) and hippocampus of rats acutely treated with 30 mg/kg or 80 mg/kg ketamine and compared with saline-treated animals to determine the effects of ketamine on amino acid neurotransmitter cycling and glial metabolism. A subanesthetic, but not anesthetic, dose of ketamine significantly increased the percentage of ¹³C-enrichments of glutamate, ?-aminobutyric acid, and glutamine in the mPFC of rats. Subanesthetic doses of ketamine increased mPFC amino acid neurotransmitter cycling, as well as neuronal and glial energy metabolism. These data add to previous reports suggesting increased mPFC levels of glutamate release, following the administration of subanesthetic doses of ketamine, are related to the drug's acute effects on cognition, perception, and mood.

SUBMITTER: Chowdhury GM

PROVIDER: S-EPMC3660962 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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¹H-[¹³C]-nuclear magnetic resonance spectroscopy measures of ketamine's effect on amino acid neurotransmitter metabolism.

Chowdhury Golam M I GM Behar Kevin L KL Cho William W Thomas Monique A MA Rothman Douglas L DL Sanacora Gerard G

Biological psychiatry 20111209 11

Ketamine has recently gained significant attention owing to its psychotomimetic and more recently discovered rapid antidepressant-like properties. ¹H-[¹³C]-nuclear magnetic resonance studies were employed to explore potential physiological processes underlying these unique effects. [1-¹³C]glucose and [2-¹³C]acetate-nuclear magnetic resonance ex vivo studies were performed on the medial prefrontal cortex (mPFC) and hippocampus of rats acutely treated with 30 mg/kg or 80 mg/kg ketamine and compare ...[more]

PMID: 22169441

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Project description:BACKGROUND:The heart's energy demand per gram of tissue is the body's highest and creatine kinase (CK) metabolism, its primary energy reserve, is compromised in common heart diseases. Here, neural-network analysis is used to test whether noninvasive phosphorus (31P) cardiovascular magnetic resonance spectroscopy (CMRS) measurements of cardiac adenosine triphosphate (ATP) energy, phosphocreatine (PCr), the first-order CK reaction rate kf, and the rate of ATP synthesis through CK (CK flux), can predict specific human heart disease and clinical severity. METHODS:The data comprised the extant 178 complete sets of PCr and ATP concentrations, kf, and CK flux data from human CMRS studies performed on clinical 1.5 and 3 Tesla scanners. Healthy subjects and patients with nonischemic cardiomyopathy, dilated (DCM) or hypertrophic disease, New York Heart Association (NYHA) class I-IV heart failure (HF), or with anterior myocardial infarction are included. Three-layer neural-networks were created to classify disease and to differentiate DCM, hypertrophy and clinical NYHA class in HF patients using leave-one-out training. Network performance was assessed using 'confusion matrices' and 'area-under-the-curve' (AUC) analyses of 'receiver operating curves'. Possible methodological bias and network imbalance were tested by segregating 1.5 and 3 Tesla data, and by data augmentation by random interpolation of nearest neighbors, respectively. RESULTS:The network differentiated healthy, HF and non-HF cardiac disease with an overall accuracy of 84% and AUC?>?90% for each category using the four CK metabolic parameters, alone. HF patients with DCM, hypertrophy, and different NYHA severity were differentiated with ~?80% overall accuracy independent of CMRS methodology. CONCLUSIONS:While sample-size was limited in some sub-classes, a neural network classifier applied to noninvasive cardiac 31P CMRS data, could serve as a metabolic biomarker for common disease types and HF severity with clinically-relevant accuracy. Moreover, the network's ability to individually classify disease and HF severity using CK metabolism alone, implies an intimate relationship between CK metabolism and disease, with subtle underlying phenotypic differences that enable their differentiation. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT00181259.

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¹H-[¹³C]-nuclear magnetic resonance spectroscopy measures of ketamine's effect on amino acid neurotransmitter metabolism.

Publications

¹H-[¹³C]-nuclear magnetic resonance spectroscopy measures of ketamine's effect on amino acid neurotransmitter metabolism.

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