Table 1.

Norepinephrine and Animal Models of Impulsivity-related Behavior

Mechanism	Examples	Behavioral effect	Pharmacology	LC effect
NE Reuptake blockade	Atomoxetine (Bari and Aston-Jones 2013;Economidou et al. 2012;Paterson et al. 2012), reboxetine (Liu et al. 2009), nortriptyline (Roychowdhury et al. 2012)	Improve response- inhibition, working memory, decreased 5CSRT impulsivity but no effect on impulsive choice	Reversed by alpha-1, alpha-2, or beta-2 blockade	Decrease FR, reduce MHPG, decrease phasic/tonic NE release
Alpha-2 receptor stimulation	Guanfacine (Avery et al. 2000), clonidine (Birnbaum et al. 2000)	Improve attention and working memory; reverse stress-induced PFC dysfunction	Reduced by alpha-1 blockade (medial PFC) or beta-2 blockade (DL PFC)	Decrease FR, reduce MHPG, decrease tonic/phasic NE release
Alpha-2 receptor blockade	Yohimbine (Arnsten and Dudley 2005;Arnsten and Li 2005;Ma et al. 2005;Mantsch et al. 2010;Sun et al. 2010)	Increase stress- induced drug reinstatement and 5CSRT impulsivity; block beneficial effect of MPH	Reversed by beta-2 blockade or reduced CREB expression	Increase FR and MHPG; increase tonic/phasic release
Alpha-1 receptor stimulation	Phenylephrine (Arnsten et al. 1999;Birnbaum et al. 1999)	Impaired delayed alternation, working memory and attention	Reversed by alpha-1 blockade or lithium
Acute stress	Experimental or pharmacological (Arnsten 2000;Mantsch et al. 2010;Otte et al. 2005)	Increase drug reinstatement, PFC impairment	Reversed by alpha-2 agonist (all effects), beta-2 antagonist (drug reinstatement), alpha-1 antagonist, resembles yohimbine	Increase MHPG

Abbreviations: NE Norepinephrine, LC locus coeruleus, MHPG 3,methoxy,4-hydroxyphenylglycol, FR firing rate, PFC prefrontal cortex, DL Dorsolateral, 5CSRT 5-choice serial reaction time test, MPH methylphenidate