scholarly journals The α7nACh–NMDA receptor complex is involved in cue-induced reinstatement of nicotine seeking

2012 ◽  
Vol 209 (12) ◽  
pp. 2141-2147 ◽  
Author(s):  
Shupeng Li ◽  
ZhaoXia Li ◽  
Lin Pei ◽  
Anh D. Le ◽  
Fang Liu
Keyword(s):  
Smoking Cessation ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Premature Death ◽  
Self Administration ◽  
Protein Protein Interaction ◽  
Positive Effects ◽  
Formidable Challenge ◽  
Extracellular Signal ◽  
Nmda Receptor Complex

Smoking is the leading preventable cause of disease, disability, and premature death. Nicotine, the main psychoactive drug in tobacco, is one of the most heavily used addictive substances, and its continued use is driven through activation of nicotinic acetylcholine receptors (nAChRs). Despite harmful consequences, it is difficult to quit smoking because of its positive effects on mood and cognition that are strong reinforcers contributing to addiction. Furthermore, a formidable challenge for the treatment of nicotine addiction is the high vulnerability to relapse after abstinence. There is no currently available smoking cessation product able to achieve a >20% smoking cessation rate after 52 wk, and there are no medications that directly target the relapse process. We report here that the α7nAChR forms a protein complex with the NMDA glutamate receptor (NMDAR) through a direct protein–protein interaction. Chronic nicotine exposure promotes α7nAChR–NMDAR complex formation. Interestingly, administration of an interfering peptide that disrupts the α7nAChR–NMDAR complex decreased extracellular signal-regulated kinase (ERK) activity and blocked cue-induced reinstatement of nicotine seeking in rat models of relapse, without affecting nicotine self-administration or locomotor activity. Our results may provide a novel therapeutic target for the development of medications for preventing nicotine relapse.

scholarly journals Varenicline for Smoking Cessation: a Review

2016 ◽  
Vol 12 (3) ◽  
pp. 215-220
Author(s):  
G P Rauniar ◽  
A Mishra ◽  
D P Sarraf
Keyword(s):  
Smoking Cessation ◽  
Tobacco Use ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Smoking Prevalence ◽  
Meta Analysis ◽  
Developed Countries ◽  
First Line ◽  
The World ◽  
Quitting Smoking

Tobacco use is the leading cause of preventable death and disability in the world. Although gradually declining in most developed countries, the prevalence of tobacco use has increased among developing countries. Nicotine is an addictive chemical that is inhaled from the tobacco present in the cigarettes. It acts on neuronal nicotinic acetylcholine receptors within the ventral tegmental area of the brain, causing dopamine release in the nucleus accumbens which reinforces nicotine-seeking behavior. Reward through the dopaminergic system is a common thread among many drugs of addiction. According to the National Anti-Tobacco Communication Campaign Strategy for Nepal smoking prevalence in Nepal is higher (38.4%) than the smoking prevalence in the world (29%). Smoking attributable annual deaths in Nepal is estimated at nearly 14,000 (9,000 male deaths and 5,000 female deaths) for population aged 35 and over. First-line pharmacotherapies for smoking cessation are varenicline, sustained-release bupropion and various forms of nicotine replacement therapy (i.e., patch, gum, lozenge, inhaler, nasal spray). These drugs can be used as monotherapy or combination therapy for the treatment of smoking cessation. After studying the outcome of many clinical trials and meta-analysis, it is concluded that cigarette smokers taking varenicline have the most success quitting smoking as compared with those taking other first-line pharmacotherapies for treating smoking cessation.  Health Renaissance 2014;12(3): 215-220

scholarly journals Network meta-analysis: a comparison of effectiveness and safety of partial agonists of nicotinic acetylcholine receptors varenicline and cytisine for smoking cessation

2018 ◽  
Vol 16 (4) ◽  
pp. 19-32
Author(s):  
Elena V. Radchenko ◽  
Olga A. Sykhovskaya ◽  
Timofey L. Galankin ◽  
Aleksei S. Kolbin ◽  
Maria A. Smirnova
Keyword(s):  
Smoking Cessation ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Nicotinic Acetylcholine ◽  
Partial Agonists ◽  
Safety Parameters ◽  
Comparison Of Effectiveness

Background. Partial agonists of α4b2 nicotinic acetylcholine receptors are the most effective treatment strategy for tobacco smoking cessation. They are able to alleviate withdrawal symptoms and to reduce smoking satisfaction. The aim of this study was to review the efficacy and safety of nicotinic receptor partial agonists varenicline and cytisine, for smoking cessation. Methods. A search for randomized controlled trials was done using the terms (“cytisine”, “tabex”, “varenicline” or 'partial agonists of nicotinic receptors’) in MEDLINE, EMBASE, eLibrary in May 2018. Types of participants, the doses and duration of the treatments, efficacy and safety parameters, quality of randomization and blinding procedures were evaluated. Bayesian network meta-analysis was performed. Results. Cytisine overcame placebo in the 12, 24 and 52 weeks of therapy with the following odds ratios (ORs) for abstinence: 3.3 (95% CrI 1.8–5.8), 3.9 (2.4–6.7), 3.8 (CrI 1.3–11,9) accordingly. Varenicline in 2 mg/day dose overcame placebo in the 12, 24 and 52 weeks of therapy with the ORs: 4.0 (3.3–4.7), 3.1 (2.5–3.7), 2.9 (2.2–4.1) accor dingly. Varenicline in 1 mg/day dose overcame placebo in 12 and 52 weeks of therapy, the ORs were 3.0 (2.0–4.7) and 2.3 (1.3–4.4) accordingly. Varenicline in 0.5 mg/day dose overcame placebo in 12 weeks of therapy only with the OR 2.4 (1.3–4.4). Cytisine and varenicline 2 mg/day were associated with more gastrointestinal disturbances than placebo with the ORs 6.2 (2.1–22.8) and 2.4 (2.0–2.8) accordingly. Cytisine and varenicline 2 mg/day were associated with more psychiatric problems than placebo with ORs 5.2 (1.9–15.1) and 1.6 (1.3–1.9) accordingly. There was no difference in serious adverse events between the investigated drugs and placebo: OR for cytisine was 2.4 (0.8–6.8), varenicline 0.5 mg/day – 2.0 (0.5–6.6), varenicline 1.0 mg/day – 1.0 (0.3–2.7), varenicline 2 mg/day – 1.0 (0.7–1.4). Conclusion. Cytisine was proved to be as effective and safe aid for smoking cessation as varenicline.

scholarly journals Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaoying Tan ◽  
Kent Vrana ◽  
Zheng-Ming Ding
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Premature Death ◽  
The United States ◽  
Public Health Issue ◽  
Tobacco Addiction ◽  
Pharmacologically Active ◽  
A Minor ◽  
Minor Alkaloid ◽  
Insight Into

Tobacco use disorder continues to be a leading public health issue and cause of premature death in the United States. Nicotine is considered as the major tobacco alkaloid causing addiction through its actions on nicotinic acetylcholine receptors (nAChRs). Current pharmacotherapies targeting nicotine’s effects produce only modest effectiveness in promoting cessation, highlighting the critical need for a better understanding of mechanisms of nicotine addiction to inform future treatments. There is growing interest in identifying potential contributions of non-nicotine components to tobacco reinforcement. Cotinine is a minor alkaloid, but the major metabolite of nicotine that can act as a weak agonist of nAChRs. Accumulating evidence indicates that cotinine produces diverse effects and may contribute to effects of nicotine. In this review, we summarize findings implicating cotinine as a neuroactive metabolite of nicotine and discuss available evidence regarding potential mechanisms underlying its effects. Preclinical findings reveal that cotinine crosses the blood brain barrier and interacts with both nAChRs and non-nAChRs in the nervous system, and produces neuropharmacological and behavioral effects. Clinical studies suggest that cotinine is psychoactive in humans. However, reviewing evidence regarding mechanisms underlying effects of cotinine provides a mixed picture with a lack of consensus. Therefore, more research is warranted in order to provide better insight into the actions of cotinine and its contribution to tobacco addiction.

scholarly journals β2* nAChRs on VTA dopamine and GABA neurons separately mediate nicotine aversion and reward

2019 ◽  
Vol 116 (51) ◽  
pp. 25968-25973 ◽  
Author(s):  
Taryn E. Grieder ◽  
Morgane Besson ◽  
Geith Maal-Bared ◽  
Stéphanie Pons ◽  
Uwe Maskos ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Drugs Of Abuse ◽  
Neural Substrates ◽  
Dopamine Neurons ◽  
Place Conditioning ◽  
Self Administration ◽  
Gaba Neurons ◽  
Conditioned Responses ◽  
Necessary And Sufficient

Evidence shows that the neurotransmitter dopamine mediates the rewarding effects of nicotine and other drugs of abuse, while nondopaminergic neural substrates mediate the negative motivational effects. β2* nicotinic acetylcholine receptors (nAChR) are necessary and sufficient for the experience of both nicotine reward and aversion in an intra-VTA (ventral tegmental area) self-administration paradigm. We selectively reexpressed β2* nAChRs in VTA dopamine or VTA γ-amino-butyric acid (GABA) neurons in β2−/−mice to double-dissociate the aversive and rewarding conditioned responses to nicotine in nondependent mice, revealing that β2* nAChRs on VTA dopamine neurons mediate nicotine’s conditioned aversive effects, while β2* nAChRs on VTA GABA neurons mediate the conditioned rewarding effects in place-conditioning paradigms. These results stand in contrast to a purely dopaminergic reward theory, leading to a better understanding of the neurobiology of nicotine motivation and possibly to improved therapeutic treatments for smoking cessation.

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