Effects of yohimbine on cerebral blood flow, symptoms, and physiological functions in humans

Objective: Increases in adrenergic activity are associated with stress, anx iety, and other psychiatric, neurological, and medical disorders. To improv e understanding of normal CNS adrenergic function, CBF responses to adrener gic stimulation were determined. Methods: Using PET, the CBF changes after intravenous yohimbine, an alpha(2)-adrenoreceptor antagonist that produces adrenergic activation, were compared with placebo in nine healthy humans. H eart rate, blood pressure, Pace, plasma catecholamines, and symptom respons es were also determined. Results: Among nonscan variables, yohimbine produc ed significant symptom increases (including a panic attack in one subject), a decrease in Pace, due to hyperventilation, increases in systolic and dia stolic blood pressure, and a trend toward a significant norepinephrine incr ease. Among scan results, yohimbine produced a significant decrease in whol e-brain absolute CBF; regional decreases were greatest in cortical areas. M edial frontal cortex, thalamus, insular cortex, and cerebellum showed signi ficant increases after normalization to whole brain. Medial frontal CBF cha nge was correlated with increases in anxiety. A panic attack produced an in crease instead of a decrease in whole-brain CBF. Factors potentially contri buting to the observed CBF changes were critically reviewed. Specific regio nal increases were most likely due in large part to activation produced by adrenergically induced anxiety and visceral symptoms. Conclusions: This stu dy supports the relationship of anxiety and interoceptive processes with me dial frontal, insular, and thalamic activation and provides a baseline for comparison of normal yohimbine-induced CNS adrenergic activation, adrenergi cally-based symptoms, and other markers of adrenergic function to stress, e motion, and the adrenergic pathophysiologies of various CNS-related disorde rs.