Hemodynamic and metabolic changes induced by cocaine in anesthetized rat observed with multimodal functional MRI

RationalePhysiological 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.ObjectivesThis 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 (CMRO2) changes.Materials and methodsBOLD and CBF fMRI was performed, and changes in CMRO2 were estimated using the BOLD biophysical model.ResultsAfter 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 CMRO2 were heterogeneous and positive throughout the brain, ranging from 14 to 150% and 10 to 55%, respectively.ConclusionsThis 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.

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