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 twenty-three 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; 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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Limited information is available on the relationship between antisocial personality disorder (ASPD) and early filtering, or gating, of information, even though this could contribute to the repeatedly reported impairment in ASPD of higher-order information processing. In order to investigate early filtering in ASPD, we compared electrophysiological measures of auditory sensory gating assessed by the paired-click paradigm in males with ASPD (n = 37) to healthy controls (n = 28). Stimulus encoding was measured by P50, N100, and P200 auditory evoked potentials; auditory sensory gating (ASG) was measured by a reduction in amplitude of evoked potentials following click repetition. Effects were studied of co-existing past alcohol or drug use disorders, ASPD symptom counts, and trait impulsivity. Controls and ASPD did not differ in P50, N100, or P200 amplitude or ASG. Past alcohol or drug use disorders had no effect. In controls, impulsivity related to improved P50 and P200 gating. In ASPD, P50 or N100 gating was impaired with more symptoms or increased impulsivity, respectively, suggesting impaired early filtering of irrelevant information. In controls the relationship between P50 and P200 gating and impulsivity was reversed, suggesting better gating with higher impulsivity scores. This could reflect different roles of ASG in behavioral regulation in controls versus ASPD.

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