2012
DOI: 10.1176/appi.ajp.2012.11101546
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Persistent β2*-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder

Abstract: Background Modulation of nicotinic acetylcholine receptors (nAChRs), specifically α4β2 subunit containing nAChRs, may be effective in the treatment of patients with major depressive disorder (MDD). Using [123I] 5-I-A-85380 single photon emission computed tomography (SPECT), we studied β2 subunit containing nAChR (β2*-nAChR) availability in patients with MDD. In order to understand the molecular basis of the change in receptor availability, we also studied β2*-nAChR binding in postmortem samples of human brains… Show more

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Cited by 106 publications
(102 citation statements)
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References 44 publications
(46 reference statements)
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“…This result illustrates an enhanced cholinergic tone in the VTA after SD, as suggested in human depressed subjects. 20 Hence, SD alters the spontaneous activity of DA neurons, their sensitivity to nicotine and increases the cholinergic tone in the VTA. If SD and nicotine 29 induce similar alterations within the DA system, then nAChRs may be important mediators of these enduring changes and a promising therapeutic target.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…This result illustrates an enhanced cholinergic tone in the VTA after SD, as suggested in human depressed subjects. 20 Hence, SD alters the spontaneous activity of DA neurons, their sensitivity to nicotine and increases the cholinergic tone in the VTA. If SD and nicotine 29 induce similar alterations within the DA system, then nAChRs may be important mediators of these enduring changes and a promising therapeutic target.…”
Section: Resultsmentioning
confidence: 99%
“…For example, changes in nAChRs availability have been observed in patients suffering from post-traumatic stress disorders or depression. [19][20][21] Chronic social defeat stress (SD) parses the enduring behavioral abnormalities induced by stress and is believed to capture features of depressive-like states. 22 SD triggers an increase in DA VTA neuronal activity 23 that drives social avoidance.…”
Section: Introductionmentioning
confidence: 99%
“…Many etiological factors could underlie depressive disorders, including alterations in monoaminergic function, but several studies have implicated dysregulation of the cholinergic system in depression in human subjects (Janowsky et al, 1972;Risch et al, 1981). Recent human SPECT imaging studies show that depressed unipolar and bipolar subjects have increased levels of ACh throughout the brain (Saricicek et al, 2012;Hannestad et al, 2013). In humans, blocking the degradation of ACh can induce depressive symptoms even in individuals with no history of illness (Janowsky et al, 1972;Risch et al, 1981), whereas in mice, blocking ACh breakdown in the hippocampus alone is sufficient to induce depression-and anxiety-like behaviors (Mineur et al, 2013).…”
Section: Introductionmentioning
confidence: 99%
“…The cholinergic system has been a recent focus for development of novel antidepressant medications (Drevets et al, 2013;Mineur and Picciotto, 2010;Picciotto et al, 2012;Saricicek et al, 2012). Acetylcholine signals through muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs, respectively) and many studies of depression have focused on mAChR signaling (Cannon et al, 2011;Riemann et al, 1994); however, blockade of either mAChRs or nAChRs can reverse the depression-like effects of increased cholinergic signaling in mice (Mineur et al, 2013) and it is likely that multiple receptors can mediate the effects of cholinergic signaling on depression (Drevets et al, 2013).…”
Section: Introductionmentioning
confidence: 99%
“…5 Similar experiments could also improve understanding and treatment of depressive disorder. 4 Future toxicological and pharmacological measurements of nifene are needed to determine if nifene doses inducing significant receptor occupancies would be ethical in humans. The 0.6 nmol/kg dose used for the present experiments resulted in a4b2* nAChR occupancies of roughly 70%; however, saturation of these receptors has been reported with no adverse side effects in 2-[ 18 F]FA smoking studies.…”
Section: Analysis With Compartment Modelingmentioning
confidence: 99%