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| Hypothesis |
| Nicotinic acetylcholine receptors as targets for antidepressants |
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| R D Shytle1,2,3,4,5,6,7, A A Silver2,3, R J Lukas8, M B Newman1,6, D V Sheehan7 and P R Sanberg1,2,3,4,5,6,7 |
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1Center for Aging and Brain Repair, University of South Florida College of Medicine, Tampa, FL, USA
2Center for Infant and Child Development, University of South Florida College of Medicine, Tampa, FL, USA
3Departments of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine, Tampa, FL, USA
4Neurosurgery, University of South Florida College of Medicine, Tampa, FL, USA
5Pharmacology, University of South Florida College of Medicine, Tampa, FL, USA
6Psychology, University of South Florida College of Medicine, Tampa, FL, USA
7Neuroscience Program, University of South Florida College of Medicine, Tampa, FL, USA
8Division of Neurobiology, Barrow Neurological Institute, Phoenix, AZ, USA
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Correspondence to: R D Shytle, PhD, Center for Aging and Brain Repair, MDC-78, Departments of Neurosurgery, Psychiatry, and Neuroscience Program, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL 33613, USA. E-mail: dshytle@hsc.usf.edu |
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| Abstract |
| While the monoamine deficiency hypothesis of depression is still most commonly used to explain the actions of antidepressant drugs, a growing body of evidence has accumulated that is not adequately explained by the hypothesis. This article draws attention to contributions from another apparently common pharmacological property of antidepressant medications¾the inhibition of nicotinic acetylcholine receptors (nAChR). Evidence is presented suggesting the hypercholinergic neurotransmission, which is associated with depressed mood states, may be mediated through excessive neuronal nicotinic receptor activation and that the therapeutic actions of many antidepressants may be, in part, mediated through inhibition of these receptors. In support of this hypothesis, preliminary evidence is presented suggesting that the potent, centrally acting nAChR antagonist, mecamylamine, which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder. If this hypothesis is supported by further preclinical and clinical research, nicotinic acetylcholine receptor antagonists may represent a novel class of therapeutic agents for treating mood disorders. Molecular Psychiatry (2002) 7, 525-535. doi:10.1038/sj.mp.4001035 |
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| Keywords |
| nicotinic; mechanism; antidepressant; cholinergic; depression |
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| Received 17 July 2001; revised 5 November 2001; accepted 13 November 2001 |
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| 2002, Volume 7, Number 6, Pages 525-535 |
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