The phenylephrine blood pressure clamp in pharmacologic magnetic resonance imaging: reduction of systemic confounds and improved detectability of drug-induced BOLD signal changes

Rationale: Peripheral physiologic changes accompany many central pharmacologic manipulations and can interact with brain activity and cerebral perfusion in complex ways. This considerably complicates the interpretation of drug-induced brain activity changes. Objectives: To evaluate a method whereby drug-induced blood pressure (BP) changes are prevented. Methods: A continuously adjusted infusion of the peripheral vasoconstrictor phenylephrine (PEP) was used to counter-regulate BP changes elicited by application of the dopamine receptor agonist apomorphine (APO) in the rat. Central effects of APO were measured using pharmacologic magnetic resonance imaging (phMRI) with blood oxygenation level dependent (BOLD) contrast at a field strength of 7 T. Results: Compared to a NOPEP control group, the PEP blood pressure clamp successfully prevented BP changes and improved the detectability of central APO effects. Moreover, APO-induced central changes no longer correlated with BP time courses. Conclusions: The method is suitable for isolating central drug effects from peripherally originating (BP) con-founds in high-field functional magnetic resonance imaging (fMRI) studies. It may also be useful in fMRI studies of autonomic regulation, cognition, and emotion if the experimental manipulation entails BP changes.