Noradrenergic modulation of working memory and emotional memory in humans

Rationale: Noradrenaline (NA) is implicated in arousal. Working memory is dependent upon prefrontal cortex, and moderate levels of NA are thought to facilitate working memory whereas higher levels during extreme stress may impair working memory and engage more posterior cortical and sub-cortical circuitry. The NA system also influences emotional memory via modulation of the amygdalae and related mediotemporal structures. NA dysfunction and abnormalities in arousal-dependent memory functions are evident in a variety of neuropsychiatric illnesses. Objectives: The authors provide a concise overview of pharmacological studies that have investigated effects of selective NA manipulations on working memory and emotional memory functions in healthy human volunteers. Materials and methods: Selection of relevant peer-reviewed publications was based on a PubMed search. Results: Studies to date indicate that: (1) the beta-blocker propranolol impaired working and emotional memory, (2) clonidine frequently impaired working memory, and (3) reboxetine, a selective noradrenaline reuptake inhibitor, enhanced emotional memory for positive material. Conclusions: Improved understanding of coupling between NA, cortico-subcortical circuitry and human mnemonic functions will suggest novel therapeutic directions for the treatment of neuropsychiatric conditions, such as attention deficit hyperactivity disorder and post-traumatic stress disorder. Future research directions are discussed in relation to neuroimaging techniques, functional central nervous system polymorphisms and study designs.