Hemodynamic and metabolic changes induced by cocaine in anesthetized rat observed with multimodal functional MRI.
BACKGROUND
Physiological changes (such as heart rate and respiration rate) associated with strong pharmacological stimuli could change the blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) mapping signals, independent of neural activity.


OBJECTIVE
This study investigates whether the physiological changes per se associated with systemic cocaine administration (1 mg/kg) contaminate the BOLD fMRI signals by measuring BOLD and cerebral blood flow (CBF) fMRI and estimating the cerebral metabolic rate of oxygen (CMRO(2)) changes.


METHODS
BOLD and CBF fMRI was performed, and changes in CMRO(2) were estimated using the BOLD biophysical model.


RESULTS
After systemic cocaine administration, blood pressure, heart rate, and respiration rate increased, fMRI signals remained elevated after physiological parameters had returned to baseline. Cocaine induced changes in the BOLD signal within regions of the reward pathway that were heterogeneous and ranged from -1.2 to 5.4%, and negative changes in BOLD were observed along the cortical surface. Changes in CBF and estimated CMRO(2) were heterogeneous and positive throughout the brain, ranging from 14 to 150% and 10 to 55%, respectively.


CONCLUSIONS
This study demonstrates a valuable tool to investigate the physiological and biophysical basis of drug action on the central nervous system, offering the means to distinguish the physiological from neural sources of the BOLD fMRI signal.
Center for Comparative Neuroimaging, University of Massachusetts, Worcester, MA, USA.
Karl F
KF
Schmidt
Marcelo
M
Febo
Qiang
Q
Shen
Feng
F
Luo
Kenneth M
KM
Sicard
Craig F
CF
Ferris
Elliot A
EA
Stein
Timothy Q
TQ
Duong
D000465:Algorithms; D000758:Anesthesia; D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D006439:Hemodynamics / Q000187:drug effects*; D006935:Hypercapnia / Q000378:metabolism; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
D003042:Cocaine; D010100:Oxygen