Pharmacological MRI in awake rats predicts selective binding of alpha(4)beta(2) nicotinic receptors.

Pharmacological MRI in awake rats predicts selective binding of alpha(4)beta(2) nicotinic receptors. Research Abstract Details 

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Pharmacological MRI in awake rats predicts selective binding of alpha(4)beta(2) nicotinic receptors. Abstract Text:

Chih-Liang Chin,James R Pauly,Bruce W Surber,Pamela D Skoubis,Steve McGaraughty,Vincent P Hradil,Yanping Luo,Bryan F Cox,Gerard B Fox,

Neuronal nicotinic receptors are the subject of intensive research focused on developing novel therapies for drug abuse, neurocognitive disorders, neurodegenerative diseases, and pain. In this study, we have applied pharmacological magnetic resonance imaging (phMRI) in awake rats to map functional brain responses to the selective alpha(4)beta(2) nicotinic receptor agonists, A-85380, and ABT-594. Moreover, we have validated our methods by comparison with autoradiography using [(3)H]-A-85380 and [(3)H]-ABT-594. Under awake conditions (no anesthesia during scanning) where rats were habituated to the imaging environment, both compounds increased regional cerebral blood volume (rCBV) across multiple brain regions that closely matched regional brain receptor distribution with the same tritiated compounds. In addition, regional ABT-594-induced rCBV changes under awake conditions were also derived and characterized using a pharmacological model. Area-under-curve and maximum rCBV changes in brain were found to be dose-related and region-specific, and corresponded well with the known preclinical behavioral profile of this drug. In contrast, under conditions of alpha-chloralose anesthesia where physiological variables were maintained within normal ranges, increases in rCBV induced by ABT-594 were primarily restricted to some cortical areas and did not agree well with autoradiography data. Our data demonstrate the utility of using phMRI in awake animals to characterize selective pharmacological action but also highlight an important confound (anesthesia) that is rarely considered in preclinical phMRI studies. Synapse 62:159-168, 2008. (c) 2007 Wiley-Liss, Inc.

Pharmacological MRI in awake rats predicts selective binding of alpha(4)beta(2) nicotinic receptors. Publishing Authors By Initials

CL Chin,JR Pauly,BW Surber,PD Skoubis,S McGaraughty,VP Hradil,Y Luo,BF Cox,GB Fox,

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Pharmacological MRI in awake rats predicts selective binding of alpha(4)beta(2) nicotinic receptors. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Synapse (New York, N.Y.)

VOLUME: 62

Page Numbers: 159-68

Journal Abbreviation: Synapse

ISSN: 0887-4476

DAY: 8

MONTH: Mar

YEAR: 2008

Pharmacological MRI in awake rats predicts selective binding of alpha(4)beta(2) nicotinic receptors. Information

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LANGUAGE: eng

NlmUniqueID: 8806914

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Grant and Affiliation Information for Pharmacological MRI in awake rats predicts selective binding of alpha(4)beta(2) nicotinic receptors.

AFFILIATION: Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064.

Country: United States

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MEDLINETA: Synapse

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