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Randomized Controlled Trial
. 2013 Sep;229(1):83-94.
doi: 10.1007/s00213-013-3088-7. Epub 2013 Apr 6.

Norepinephrine and Impulsivity: Effects of Acute Yohimbine

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Free PMC article
Randomized Controlled Trial

Norepinephrine and Impulsivity: Effects of Acute Yohimbine

Alan C Swann et al. Psychopharmacology (Berl). .
Free PMC article

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.

Conflict of interest statement

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.

Figures

Fig 1
Fig 1. Yohimbine Effects on Plasma Catecholamine Metabolites
The Figure shows net changes in plasma (A) MHPG, (B) VMA, and (C) HVA, in ng/ml, with standard errors. Statistics are summarized in Table 1. *: Different from baseline, Newman-Keuls test, p < 0.05.
Fig 2
Fig 2. Yohimbine Effects on Blood Pressure and Pulse
The Figure shows net changes in (A) systolic and (B) diastolic blood pressure in mm Hg, and (C) pulse rate in beats/min, with standard errors. Statistics are summarized in Table 1. *: Different from baseline, Newman-Keuls test, p < 0.05.
Fig 3
Fig 3. Yohimbine Effects on Immediate Memory Task Performance
The Figure shows net changes in (A) percent commission errors, (B) commission errors/correct detections (CE/CD) ratio, (C) reaction time to a commission error (CE, in ms),and (D) response bias, with standard errors. Negative bias scores represent impulsive responding. Statistics are summarized in Table 2. *: Different from baseline, Newman-Keuls test, p < 0.05.

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