The role of the α7 nicotinic receptor in cognitive processing of persons with schizophrenia

Cognitive abilities are established as major deficits in those with schizophrenia and represent significant impediments toward successful psychosocial functioning within the community. Pharmacological treatments have historically focused on reducing the positive and negative symptoms of schizophrenia, with recent increased attention to developing agents to improve cognition as a treatment outcome. This review will highlight the recent advances in developing agents that act at neuronal α7 nicotinic acetylcholine receptors (nAChRs).

A number of agents have demonstrated improvements in cognitive deficits in studies using both preclinical and clinical models. Evidence suggests that α7 nAChR activation impacts rule acquisition and initial learning in preclinical models. Preclinical studies indicate improved spatial working memory and reversal of phencyclidine-induced learning and memory deficits. Clinical studies indicate normalization of neuronal default network activity using functional magnetic resonance imaging methods. In addition, research on new agents developed to improve cognition suggests improved cognitive functioning in multiple domains (e.g., attention, memory, executive functioning, sensory gating and overall cognition) and promising safety profiles of additional agents.

Improvements in cognitive functioning within preclinical and clinical studies of schizophrenia are evident through the use of α7 nAChR agonists, while positive allosteric modulators may gain increased attention in the future.