This is a request for 5 years of funding through the """"""""Mentored Quantitative Research Career Award"""""""" (K25) mechanism. The applicant, a biophysicist/electrical engineer, proposes a program of training in neuroscience and pharmacology. The long term goal of the applicant is to become an independent and interdisciplinary investigator, skilled in the application of magnetic resonance methods for the study of substance abuse research. The research component of this award will develop and improve functional magnetic resonance imaging (fMRI) techniques for the study of substance abuse and addiction in human subjects. These techniques will be applied to study the effects of cocaine administration in humans. Cocaine abuse is a serious public health problem having important psychiatric, medical, and drug abuse policy implications. Acute administration of cocaine alters central nervous system (CNS) neuronal activity and cerebral blood flow; chronic use of cocaine can lead to long term neuronal and behavioral changes, as well as to alterations in cerebral vascular function. fMRI uses blood oxygenation changes to estimate neuronal activity, with a temporal resolution of several seconds and spatial resolution of a few millimeters. However, signal to noise ratio (SNR) and temporal resolution limits put constraints on the parameters that can currently be measured in vivo. Three separate technical development efforts are proposed. First, a phased array echoplanar imaging system, optimized for the study of brain regions which may mediate the rewarding effects of cocaine, will be implemented on a 4 Tesla MR scanner. This system will significantly increase the SNR of fMRI, and allow the detection of cocaine-induced alterations in neuronal activity in ventral striatum, thalamus, and posterior neocortex in individual subjects. Second, a method for rapidly and simultaneously assessing the relative BOLD activation resulting from blue and red light will be developed with a time resolution of at least one multicolor measurement per minute to determine the relationship between cocaine's effects on color visual processing (a proxy for dopaminergic alterations) and activation in other brain regions. Third, a set of experimental studies will be conducted to determine the relationship between EEG alpha activity (a surrogate marker for drug-induced euphoria) and the BOLD photic response. This study may aid in the development of magnetic resonance methods for assessing EEG alpha activity, giving an objective measure of the euphorigenic effects of various drugs. The long term goals of this research are to provide a better understanding of the phenomenon of cocaine abuse so that better prevention and treatment strategies can be developed and evaluated.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25DA014013-03
Application #
6653022
Study Section
Special Emphasis Panel (ZDA1-RXL-E (07))
Program Officer
Grant, Steven J
Project Start
2001-05-01
Project End
2006-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
3
Fiscal Year
2003
Total Cost
$133,572
Indirect Cost
Name
Mc Lean Hospital (Belmont, MA)
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Kaufman, Marc J; Janes, Amy C; Frederick, Blaise deB et al. (2013) A method for conducting functional MRI studies in alert nonhuman primates: initial results with opioid agonists in male cynomolgus monkeys. Exp Clin Psychopharmacol 21:323-31
Lindsey, Kimberly P; Bracken, Bethany K; Maclean, Robert R et al. (2013) Nicotine content and abstinence state have different effects on subjective ratings of positive versus negative reinforcement from smoking. Pharmacol Biochem Behav 103:710-6
Lindsey, K P; Lukas, S E; MacLean, R R et al. (2009) Design and validation of an improved nonferrous smoking device for self-administration of smoked drugs with concurrent fMRI neuroimaging. Clin EEG Neurosci 40:21-30
Frederick, Blaise deB; Lindsey, Kimberly P; Nickerson, Lisa D et al. (2007) An MR-compatible device for delivering smoked marijuana during functional imaging. Pharmacol Biochem Behav 87:81-9
Cowan, Ronald L; Bolo, Nicolas R; Dietrich, Mary et al. (2007) Occipital cortical proton MRS at 4 Tesla in human moderate MDMA polydrug users. Psychiatry Res 155:179-88
Friedman, Seth D; Jensen, J Eric; Frederick, Blaise B et al. (2007) Brain changes to hypocapnia using rapidly interleaved phosphorus-proton magnetic resonance spectroscopy at 4 T. J Cereb Blood Flow Metab 27:646-53
Moore, Constance M; Wardrop, Megan; deB Frederick, Blaise et al. (2006) Topiramate raises anterior cingulate cortex glutamine levels in healthy men; a 4.0 T magnetic resonance spectroscopy study. Psychopharmacology (Berl) 188:236-43
Cowan, R L; Haga, E; deB Frederick, B et al. (2006) MDMA use is associated with increased spatial BOLD fMRI visual cortex activation in human MDMA users. Pharmacol Biochem Behav 84:219-28
Schneider, E; Bolo, N R; Frederick, B et al. (2006) Magnetic resonance spectroscopy for measuring the biodistribution and in situ in vivo pharmacokinetics of fluorinated compounds: validation using an investigation of liver and heart disposition of tecastemizole. J Clin Pharm Ther 31:261-73
Prescot, Andrew P; de B Frederick, Blaise; Wang, Liqun et al. (2006) In vivo detection of brain glycine with echo-time-averaged (1)H magnetic resonance spectroscopy at 4.0 T. Magn Reson Med 55:681-6

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