Noradrenergic modulation of cognition: Therapeutic implications

The noradrenaline (norepinephrine) system exerts profound influences on cognition via ascending projections to the forebrain, mostly originating from the locus coeruleus. This paper provides an overview of available infrahuman and healthy human studies, exploring the effects of specific noradrenergic manipulations on dissociable cognitive functions, including attention, working memory, cognitive flexibility, response inhibition and emotional memory. Remarkable parallels across species have been reported which may account for the mechanisms by which noradrenergic medications exert their beneficial effects in disorders such as depression and attention-deficit hyperactivity disorder (ADHD). The literature is discussed in relation to prevailing models of noradrenergic influences over cognition and novel therapeutic directions, including in relation to investigating the effects of noradrenergic manipulations on other disorders characterized by impulsivity, and dementias. Unanswered questions are also highlighted, along with key avenues for future research, both proof-of-concept and clinical.