title: Norepinephrine and impulsivity: effects of acute yohimbine.
abstract: BACKGROUND
  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.
authors.affiliation: 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@uth.tmc.edu
authors.forename: Alan C
authors.initials: AC
authors.lastname: Swann
authors.forename: Marijn
authors.initials: M
authors.lastname: Lijffijt
authors.forename: Scott D
authors.initials: SD
authors.lastname: Lane
authors.forename: Blake
authors.initials: B
authors.lastname: Cox
authors.forename: Joel L
authors.initials: JL
authors.lastname: Steinberg
authors.forename: F Gerard
authors.initials: FG
authors.lastname: Moeller
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007175:Impulsive Behavior / Q000097:blood* / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D002395:Catecholamines; D015016:Yohimbine; D009638:Norepinephrine
references.citation: Brain Res. 1991 Feb 22;542(1):8-14
references.pmid: 2054662
references.citation: Prog Brain Res. 2000;126:183-92
references.pmid: 11105647
references.citation: Arch Gen Psychiatry. 1991 Sep;48(9):807-12
references.pmid: 1929771
references.citation: J Psychiatr Res. 2009 Aug;43(12):1057-63
references.pmid: 19345957
references.citation: Biol Psychiatry. 2005 Jan 15;57(2):192-5
references.pmid: 15652880
references.citation: Psychopharmacology (Berl). 2009 Jun;204(3):477-88
references.pmid: 19229522
references.citation: Life Sci. 1982 Jun 7;30(23):2033-41
references.pmid: 6287139
references.citation: Psychiatry Res. 1988 Feb;23(2):119-30
references.pmid: 3363020
references.citation: Neuropsychopharmacology. 2012 Aug;37(9):2057-66
references.pmid: 22510726
references.citation: Neuroscience. 2004;125(3):683-90
references.pmid: 15099682
references.citation: J Clin Endocrinol Metab. 2000 Nov;85(11):4138-45
references.pmid: 11095445
references.citation: Psychopharmacology (Berl). 2012 Jul;222(2):237-45
references.pmid: 22271065
references.citation: Pharmacol Biochem Behav. 2011 Aug;99(2):211-6
references.pmid: 21295057
references.citation: J Child Psychol Psychiatry. 2003 Nov;44(8):1145-57
references.pmid: 14626456
references.citation: Psychopharmacology (Berl). 2012 Jan;219(2):285-301
references.pmid: 21809008
references.citation: Biol Psychiatry. 2005 Jan 1;57(1):27-32
references.pmid: 15607297
references.citation: Biol Psychiatry. 1999 Nov 1;46(9):1266-74
references.pmid: 10560032
references.citation: Psychiatry Res. 1996 Jun 26;63(1):7-16
references.pmid: 8832769
references.citation: J Gen Psychol. 2003 Jan;130(1):5-21
references.pmid: 12635853
references.citation: Nicotine Tob Res. 2011 Jul;13(7):611-5
references.pmid: 21357729
references.citation: J Affect Disord. 2011 Sep;133(1-2):221-6
references.pmid: 21550122
references.citation: J Pharmacol Exp Ther. 1968 Sep;163(1):147-62
references.pmid: 5673702
references.citation: Am J Psychiatry. 2005 Sep;162(9):1680-7
references.pmid: 16135628
references.citation: Science. 1979 Sep 7;205(4410):1025-7
references.pmid: 472724
references.citation: Biol Psychiatry. 2002 Jun 15;51(12):988-94
references.pmid: 12062883
references.citation: Neurochem Res. 1995 Apr;20(4):427-33
references.pmid: 7651580
references.citation: Neurosci Lett. 2003 Sep 18;348(3):171-4
references.pmid: 12932821
references.citation: Int J Neuropsychopharmacol. 2012 Nov;15(10):1473-87
references.pmid: 22094071
references.citation: Brain Res Brain Res Rev. 2003 Apr;42(1):33-84
references.pmid: 12668290
references.citation: J Pharmacol Exp Ther. 1991 Feb;256(2):606-13
references.pmid: 1671597
references.citation: Ann N Y Acad Sci. 1995 Jul 12;763:552-65
references.pmid: 7677373
references.citation: Brain Res Bull. 2001 Aug;55(6):761-5
references.pmid: 11595360
references.citation: Suicide Life Threat Behav. 2004 Winter;34(4):374-85
references.pmid: 15585459
references.citation: Psychopharmacology (Berl). 2000 Apr;149(3):259-68
references.pmid: 10823407
references.citation: Arch Gen Psychiatry. 1987 Apr;44(4):345-54
references.pmid: 2436590
references.citation: Psychoneuroendocrinology. 1990;15(3):217-24
references.pmid: 2255749
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1996 Nov;20(8):1353-67
references.pmid: 9004342
references.citation: Biol Psychiatry. 1995 Jul 15;38(2):74-85
references.pmid: 7578653
references.citation: Biol Psychiatry. 2005 May 15;57(10):1209-11
references.pmid: 15866563
references.citation: Psychol Med. 2009 Aug;39(8):1253-63
references.pmid: 19079809
references.citation: Neuropsychobiology. 2004;50(4):336-40
references.pmid: 15539866
references.citation: J Neurosci. 2005 Apr 27;25(17):4370-4
references.pmid: 15858063
references.citation: Biol Psychiatry. 2010 Apr 1;67(7):649-56
references.pmid: 20163788
references.citation: Neuropsychopharmacology. 2010 Oct;35(11):2165-78
references.pmid: 20613718
references.citation: Neuropharmacology. 2013 Jan;64:53-64
references.pmid: 22820275
references.citation: J Affect Disord. 2003 Jan;73(1-2):105-11
references.pmid: 12507743
references.citation: Exp Clin Psychopharmacol. 2008 Apr;16(2):124-31
references.pmid: 18489016
references.citation: Biol Psychiatry. 1999 Jan 1;45(1):26-31
references.pmid: 9894572
references.citation: Synapse. 2000 Feb;35(2):79-95
references.pmid: 10611634
references.citation: Br J Pharmacol. 2011 Oct;164(4):1301-21
references.pmid: 21410459
references.citation: Psychopharmacology (Berl). 2012 Jan;219(2):341-52
references.pmid: 21761147
references.citation: J Comp Neurol. 2005 Dec 5;493(1):99-110
references.pmid: 16254995
references.citation: Bipolar Disord. 2011 Mar;13(2):173-81
references.pmid: 21443571
references.citation: Pharmacol Biochem Behav. 2000 Nov;67(3):397-403
references.pmid: 11164065
references.citation: Psychopharmacology (Berl). 1999 Oct;146(4):348-61
references.pmid: 10550486
references.citation: Psychopharmacologia. 1975 Nov 21;44(3):215-24
references.pmid: 1824
references.citation: Anal Biochem. 1983 Jul 1;132(1):165-70
references.pmid: 6625157
references.citation: Am J Psychiatry. 2001 Nov;158(11):1783-93
references.pmid: 11691682
references.citation: J Biomed Sci. 2009 Aug 14;16:72
references.pmid: 19678962
references.citation: Biol Psychiatry. 2005 Jun 1;57(11):1377-84
references.pmid: 15950011
references.citation: Behav Brain Res. 1989 Jun 1;33(2):165-79
references.pmid: 2504222
references.citation: Eur Arch Psychiatry Clin Neurosci. 1992;241(6):345-51
references.pmid: 1504111
references.citation: Essays Neurochem Neuropharmacol. 1978;3:1-32
references.pmid: 361388
references.citation: Psychopharmacology (Berl). 2005 Jul;180(3):491-500
references.pmid: 15719216
references.citation: Alcohol. 2004 Oct-Nov;34(2-3):133-50
references.pmid: 15902907
references.citation: Behav Brain Funct. 2005 Apr 22;1(1):2
references.pmid: 15916700
references.citation: J Neurosci. 1997 Dec 1;17(23):9367-74
references.pmid: 9364082
references.citation: Neuropsychopharmacology. 2000 Sep;23(3):240-9
references.pmid: 10942848
references.citation: Am J Psychiatry. 1984 Oct;141(10):1267-8
references.pmid: 6091464
references.citation: Psychopharmacology (Berl). 2011 Feb;213(2-3):171-82
references.pmid: 20386882
references.citation: Neuroendocrinology. 1989 Sep;50(3):286-91
references.pmid: 2552342
references.citation: Neuropsychopharmacology. 2012 Jun;37(7):1656-70
references.pmid: 22334120
references.citation: Life Sci. 1980 Nov 17;27(20):1857-62
references.pmid: 7193269
references.citation: Neuropsychopharmacology. 2010 Feb;35(3):591-604
references.pmid: 19940844