Journal
BIOCHEMICAL PHARMACOLOGY
Volume 85, Issue 12, Pages 1713-1720Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2013.04.001
Keywords
Nicotinic receptors; Prefrontal cortex; Disease; Pharmacology; Cholinergic
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The prefrontal cortex (PFC) is responsible for integrating cortical and subcortical inputs to execute essential cognitive functions such as attention, working memory planning and decision-making. The importance of this brain region in regulating complex cognitive processes is underscored by a decline in PFC-mediated ability observed in aging and disease. The cholinergic system plays a vital role in cognitive function and treatments (e.g., cholinesterase inhibitors) to improve cholinergic neurotransmission provide the standard-of-care for diseases such as Alzheimer's. Nicotinic receptors (nAChRs) are a primary site of action for acetylcholine- (ACh), and the resulting pro-cognitive effects observed by stimulating nAChRs with nicotine has long been appreciated by tobacco users, prompting investigation of therapeutic development for diseases (e.g., schizophrenia, Alzheimer or attention-deficit-hyperactivity disorder) by targeting the neuronal nAChR system. Noteworthy, improvements in attention, working memory and executive processes mediated by the PFC have been reported following nicotinic agonist exposure. Relevance of these ligand gated channels in higher brain function is further supported by the association of cognitive deficits reported in humans with mutations in CHRNB2 or CHRNA7 the genes encoding for the nicotinic receptor beta 2 and alpha 7 subunits, respectively. In this work we review, in light of the latest findings, how nicotinic agonists may be acting in the PFC to influence cognitive function. (C) 2013 Elsevier Inc. All rights reserved.
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