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Norepinephrine and impulsivity: effects of acute yohimbine

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Abstract

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.

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Acknowledgments

This study was supported in part by the Pat R Rutherford, Jr. Chair in Psychiatry (ACS) and by NIH grants R01-MH69944 (ACS), K02-DA00403 (FGM), and UL1-RR024148 (CTSA; General Clinical Research Center UT Houston). We thank Martin Javors, Ph.D. (University of Texas Health Science Center at San Antonio) for performing catecholamine metabolite assays; Stephen Hecht, M.D., Department of Emergency Medicine, for assisting with medical backup; and Stacy Meier, Leslie Paith, Irshad Prasla, Tammy Souter, R.N., Anthony Zamudio, R.N., and the nursing staff of the Clinical Research Unit, for their skilled assistance.

Conflicts of interest

Dr. Swann has served on Data Safety Monitoring Boards for Pfizer Laboratories and Teva Pharmaceuticals; as a speaker for Abbott Laboratories, Cortexcongress, Merck, and Sanofi-Aventis; as a consultant for Merck; and has received grant support from Elan Pharmaceuticals and the NIH. Dr. Moeller has acted as a consultant for Boeringer Ingelheim and has received funding from the NIH. Drs. Lane and Steinberg have received funding from the NIH. Dr. Lijffijt and Mr. Cox report no potential conflicts.

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  1. Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, 1941 East Road, Room 3216, Houston, TX, 77054, USA

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

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  1. Alan C. Swann
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  2. Marijn Lijffijt
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Correspondence to Alan C. Swann.

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Swann, A.C., Lijffijt, M., Lane, S.D. et al. Norepinephrine and impulsivity: effects of acute yohimbine. Psychopharmacology 229, 83–94 (2013). https://doi.org/10.1007/s00213-013-3088-7

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