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High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness

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Abstract

Rationale

Nicotinic acetylcholine receptors (nAChRs) are a critical component of the cholinergic system of neurotransmission in the brain that modulates important physiological processes such as reward, cognition, and mood. Abnormalities in this system are accordingly implicated in multiple psychiatric illnesses, including addiction, schizophrenia, and mood disorders. There is significantly increased tobacco use, and therefore nicotine intake, in patient populations, and pharmacological agents that act on various nicotinic receptor subtypes ameliorate clinical features of these disorders. Better understanding of the molecular mechanisms underlying cholinergic dysfunction in psychiatric disease will permit more targeted design of novel therapeutic agents.

Results

The objective of this review is to describe the multiple cellular pathways through which chronic nicotine exposure regulates nAChR expression, and to juxtapose these mechanisms with evidence for altered expression of high-affinity nAChRs in human psychiatric illness. Here, we summarize multiple studies from pre-clinical animal models to human in vivo imaging and post-mortem experiments demonstrating changes in nAChR regulation and expression in psychiatric illness.

Conclusions

We conclude that a mechanistic explanation of nAChR abnormalities in psychiatric illness will arise from a fuller understanding of normal nAChR trafficking, along with the detailed study of human tissue, perhaps using novel biotechnological advances, such as induced pluripotent stem cells.

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Acknowledgments

ASL is supported by grant 5T32MH019961 and MRP is supported by grants DA014241, MH077681, and DA033945, from the National Institutes of Health.

Conflict of interest statement

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA

    Alan S. Lewis & Marina R. Picciotto

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  1. Alan S. Lewis
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  2. Marina R. Picciotto
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Correspondence to Marina R. Picciotto.

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Lewis, A.S., Picciotto, M.R. High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness. Psychopharmacology 229, 477–485 (2013). https://doi.org/10.1007/s00213-013-3126-5

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