Journal Article

Norepinephrine and impulsivity: effects of acute yohimbine

Steinberg, Joel L., Cox, Blake, Moeller, F. Gerard, Lijffijt, Marijn, Lane, Scott D., Swann, Alan C.

2013

Overview

Rationale Rapid-response impulsivity, characterized by inability to withhold response to a stimulus until it is adequately appraised, is associated with risky behavior and may be increased in a state-dependent manner by norepinephrine. Objective We assessed effects of yohimbine, which increases norepinephrine release by blocking alpha-2 noradrenergic receptors, on plasma catecholamine metabolites, blood pressure, subjective symptoms, and laboratory-measured rapid-response impulsivity. Methods Subjects were 23 healthy controls recruited from the community, with normal physical examination and ECG, and negative history for hypertension, cardiovascular illness, and axis I or II disorder. Blood pressure, pulse, and behavioral measures were obtained before and periodically after 0.4 mg/kg oral yohimbine or placebo in a randomized, counterbalanced design. Metabolites of norepinephrine [3-methoxy-4-hydroxyphenylglycol (MHPG) and vanillylmandelic acid (VMA)] and dopamine [homovanillic acid (HVA)] were measured by high-pressure liquid chromatography with electrochemical detection. Rapid-response impulsivity was measured by commission errors and reaction times on the immediate memory task (IMT), a continuous performance test designed to measure impulsivity and attention. Results Yohimbine increased plasma MHPG and VMA but not HVA. Yohimbine increased systolic and diastolic blood pressure and pulse rate. On the IMT, yohimbine increased impulsive errors and impulsive response bias and accelerated reaction times. Yohimbine-associated increase in plasma MHPG correlated with increased impulsive response rates. Time courses varied; effects on blood pressure generally preceded those on metabolites and test performance. Conclusions These effects are consistent with increased rapid-response impulsivity after pharmacological noradrenergic stimulation in healthy controls. Labile noradrenergic responses, or increased sensitivity to norepinephrine, may increase risk for impulsive behavior.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Adult / Behavior / Biomedical and Life Sciences / Biomedicine / Blood pressure / Blood Pressure - drug effects / Blood Pressure - physiology / Catecholamines - blood / Dosage and administration / Double-Blind Method / Drug interactions / Female / Heart Rate - drug effects / Heart Rate - physiology / Humans / Impulsive Behavior - blood / Impulsive Behavior - chemically induced / Male / Metabolites / Middle Aged / Neurosciences / Noradrenaline / Norepinephrine - blood / Original Investigation / Pharmacology/Toxicology / Psychiatry / Psychological aspects / Psychopharmacology / Reaction Time - drug effects / Reaction Time - physiology / Stimulants / Yohimbine / Yohimbine - adverse effects / Yohimbine - pharmacology / Young Adult