β2 Nicotinic acetylcholine receptor availability in post-traumatic stress disorder

Czermak, Christoph; Staley, Julie K.; Kasserman, Sue; Young, Theresa A.; Henry, Shannan; Tamagnan, Gilles; Seibyl, John; Krystal, John H.; Neumeister, Alexander

doi:10.1017/s1461145707008152

Cited by 29 publications

(19 citation statements)

References 22 publications

(26 reference statements)

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“…In addition, infusions of the high-affinity nAChR antagonist DhβE into the dorsal hippocampus precipitated withdrawal deficits in both contextual (Davis & Gould, 2009) and trace fear learning (Raybuck & Gould, 2009). Overall, in line with the human studies linking hippocampal β2 nAChRs with PTSD (Czermak et al, 2008), results from the studies using acute, chronic, and withdrawal from chronic nicotine suggest that the effects of nicotine on hippocampus-dependent fear memories require the activation and upregulation of the high-affinity β2-containing nAChRs.…”

Section: Involvement Of Nachrs In Anxiety and Anxiety Disorderssupporting

confidence: 64%

“…Investigating the direct relationship between nAChRs and PTSD by using the radiotracer [ 123 I]5-IA-85380 ([ 123 I]5-IA) and single-photon emission computed tomography, Czermak et al (2008) found that PTSD patients who never smoked showed significantly higher β2 nAChR density in the mesiotemporal cortex including the amygdala and hippocampus compared to healthy individuals who never smoked. Furthermore, the same study found a significant correlation between β2 nAChR binding in the thalamus and the reexperiencing symptom among the PTSD patients.…”

Section: Involvement Of Nachrs In Anxiety and Anxiety Disordersmentioning

confidence: 99%

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Nicotine Addiction and Psychiatric Disorders

Kutlu

Parikh

Gould

2015

International Review of Neurobiology

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Even though smoking rates have long been on the decline, nicotine addiction still affects 20% of the US population today. Moreover, nicotine dependence shows high comorbidity with many mental illnesses including, but are not limited to, attention deficit hyperactivity disorder, anxiety disorders, and depression. The reason for the high rates of smoking in patients with mental illnesses may relate to attempts to self-medicate with nicotine. While nicotine may alleviate the symptoms of mental disorders, nicotine abstinence has been shown to worsen the symptoms of these disorders. In this chapter, we review the studies from animal and human research examining the bidirectional relationship between nicotine and attention deficit hyperactivity disorder, anxiety disorders, and depression as well as studies examining the roles of specific subunits of nicotinic acetylcholine receptors (nAChRs) in the interaction between nicotine and these mental illnesses. The results of these studies suggest that activation, desensitization, and upregulation of nAChRs modulate the effects of nicotine on mental illnesses.

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Section: Involvement Of Nachrs In Anxiety and Anxiety Disorderssupporting

confidence: 64%

Section: Involvement Of Nachrs In Anxiety and Anxiety Disordersmentioning

confidence: 99%

Nicotine Addiction and Psychiatric Disorders

Kutlu

Parikh

Gould

2015

International Review of Neurobiology

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“…Importantly, using the radiotracer [ 123 I]5-IA-85380 and single-photon emission computed tomography (SPECT), Czermak et al (2008) demonstrated that non-smoker PTSD patients showed a significantly higher density of β2 nAChRs in the mesiotemporal cortex, including the amygdala and hippocampus, compared to non-smoker healthy individuals. These brain regions are widely related to pathogenesis of PTSD (Martin et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

High-affinity α4β2 nicotinic receptors mediate the impairing effects of acute nicotine on contextual fear extinction

Kutlu

Holliday

Gould

2016

Neurobiology of Learning and Memory

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Previously, studies from our lab have shown that while acute nicotine administered prior to training and testing enhances contextual fear conditioning, acute nicotine injections prior to extinction sessions impair extinction of contextual fear. Although there is also strong evidence showing that the acute nicotine’s enhancing effects on contextual fear conditioning require high-affinity α4β2 nicotinic acetylcholine receptors (nAChRs), it is unknown which nAChR subtypes are involved in the acute nicotine-induced impairment of contextual fear extinction. In this study, we investigated the effects of acute nicotine administration on contextual fear extinction in knock-out (KO) mice lacking α4, β2 or α7 subtypes of nAChRs and their wild-type (WT) littermates. Both KO and WT mice were first trained and tested for contextual fear conditioning and received a daily contextual extinction session for 4 days. Subjects received intraperitoneal injections of nicotine (0.18 mg/kg) or saline 2–4 mins prior to each extinction session. Our results showed that the that mice lack α4 and β2 subtypes of nAChRs showed normal contextual fear extinction but not the acute nicotine-induced impairment while the mice that lack the α7 subtype showed both normal contextual extinction and nicotine-induced impairment of contextual extinction. In addition, control experiments showed that acute nicotine-induced impairment of contextual fear extinction persisted when nicotine administration was ceased and repeated acute nicotine administrations alone did not induce freezing behavior in the absence of context-shock learning. These results clearly demonstrate that high-affinity α4β2 nAChRs are necessary for the effects of acute nicotine on contextual fear extinction.

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“…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%

Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity

et al. 2017

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Epidemiological studies report strong association between mood disorders and tobacco addiction. This high comorbidity requires adequate treatment but the underlying mechanisms are unknown. We demonstrate that nicotine exposure, independent of drug withdrawal effects, increases stress sensitivity, a major risk factor in mood disorders. Nicotine and stress concur to induce long-lasting cellular adaptations within the dopamine (DA) system. This interplay is underpinned by marked remodeling of nicotinic systems, causing increased ventral tegmental area (VTA) DA neurons' activity and stress-related behaviors, such as social aversion. Blocking β2 or α7 nicotinic acetylcholine receptors (nAChRs) prevents, respectively, the development and the expression of social stress-induced neuroadaptations; conversely, facilitating α7 nAChRs activation specifically in the VTA promotes stress-induced cellular and behavioral maladaptations. Our work unravels a complex nicotine-stress bidirectional interplay and identifies α7 nAChRs as a promising therapeutic target for stress-related psychiatric disorders.

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β2 Nicotinic acetylcholine receptor availability in post-traumatic stress disorder

Cited by 29 publications

References 22 publications

Nicotine Addiction and Psychiatric Disorders

Nicotine Addiction and Psychiatric Disorders

High-affinity α4β2 nicotinic receptors mediate the impairing effects of acute nicotine on contextual fear extinction

Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity

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