Pharmacological manipulation of human working memory

Rationale. The goal of this paper is to briefly overview human studies that have examined pharmacological agents designed to enhance working memory function, with the idea of providing clues as to promising avenues to follow for the development of drugs likely to enhance working memory and other cognitive processes in individuals with schizophrenia. Objectives. We reviewed the studies that have used pharmacological agents designed to target the dopamine system, the noradrenergic system, the acetycholine system, the serotonin system, and the glycine site on NMDA receptors. Results. There are a large number of studies suggesting that dopamine agents can enhance working memory, though there remain conflicting issues regarding the role that baseline performance plays in modulating the influence of drug and the importance of different dopamine receptors. There is also consistent evidence that cholinesterase inhibitors can enhance working memory function, potentially through improved encoding of the information. There is less consistent evidence that noradrenergic alpha-2 agonists consistently improve working memory in humans, despite the large animal literature suggesting that these agents should have a beneficial effect on memory. As of yet, there is little evidence that agents targeting the glycine site of the NMDA receptor improve working memory, and data to suggest that enhancement of the serotonin system impairs working memory. Conclusions. Compounds geared towards enhancing the dopamine system and the acetycholine system remain promising avenues for the development of pro-cognitive drugs, though further work is clearly needed on developing agents that may more selectively target specific receptors.