Original Article
Neuropsychopharmacology (2006) 31, 2683–2691. doi:10.1038/sj.npp.1301023; published online 11 January 2006
Preclinical Research
In Vivo Quantification of Ethanol Kinetics in Rat Brain
Elfar Adalsteinsson1,2, Edith V Sullivan3, Dirk Mayer4 and Adolf Pfefferbaum3,5
- 1Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, MA, USA
- 2Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA
- 3Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
- 4Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA
- 5Neuroscience Program, SRI International, Menlo Park, CA, USA
Correspondence: Dr A Pfefferbaum, Neuroscience Program, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA. Tel: +650 859 2927; Fax: +650 859 2743; E-mail: dolf@synapse.sri.com
Received 15 July 2005; Revised 28 November 2005; Accepted 29 November 2005; Published online 11 January 2006.
Abstract
Proton magnetic resonance spectroscopy was used at 3T to measure the uptake and clearance of brain ethanol in rats after bolus intraperitoneal (i.p.) or intragastric (i.g.) alcohol injection, and to estimate the effects of acute alcohol on brain metabolites. The observation duration was 1–1.5 h with temporal resolution of alcohol sampling ranging from 4 s–4 min. The observed time course of alcohol brain concentration followed a consistent pattern characterized by a rapid absorption, an intermediate distribution, and a slower clearance that approached a linear decay. In a sample of eight healthy Wistar rats, the intercept of the linear clearance term, extrapolated back to the time of injection, correlated well with the administered dose per unit of lean body mass. Alcohol concentration estimation based on spectroscopically measured clearance was compared with blood alcohol levels from blood samples at the end of observation, and were in good agreement with the administered dose. Serial proton spectroscopy measurements provide a valid in vivo method for quantifying brain alcohol uptake and elimination kinetics in real time.
Keywords:
MR spectroscopy, alcohol, ethanol, glutamate, rat, imaging
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