Nicotinic Cholinergic Receptor Binding Sites in the Brain: Regulation in Vivo

Schwartz, Rochelle D.; Kellar, Kenneth J.

doi:10.1126/science.6828889

Cited by 460 publications

(291 citation statements)

References 13 publications

Supporting

Mentioning

270

Contrasting

Unclassified

Order By: Relevance

“…We found that knock-down of c-Fos inhibited the nicotine-induced excitatory status of cells but not the expression of TH ( Figure 8A and A1), indicating that the effect of c-Fos on the excitatory status of cells and neuron-specific adaptation induced by nicotine was not mediated by the regulation of TH expression. The binding sites of the 3 H nicotine in the central nervous system as well as the number of cells that can react to nicotine were increased after prolonged nicotine exposure [37,38]. Our present study indicates that L-theanine can inhibit the rewarding effects in the mouse CPP model and reduce the excitatory status of cells induced by nicotine.…”

Section: Discussionsupporting

confidence: 51%

L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway

Yan

Zhao

et al. 2012

Sci. China Life Sci.

View full text Add to dashboard Cite

In this study, the inhibitory effect of L-theanine, an amino acid derivative of tea, on the rewarding effects of nicotine and its underlying mechanisms of action were studied. We found that L-theanine inhibited the rewarding effects of nicotine in a conditioned place preference (CPP) model of the mouse and reduced the excitatory status induced by nicotine in SH-SY5Y cells to the same extent as the nicotine receptor inhibitor dihydro-beta-erythroidine (DHE). Further studies using high performance liquid chromatography, western blotting and immunofluorescence staining analyses showed that L-theanine significantly inhibited nicotine-induced tyrosine hydroxylase (TH) expression and dopamine production in the midbrain of mice. L-theanine treatment also reduced the upregulation of the  4,  2 and  7 nicotine acetylcholine receptor (nAChR) subunits induced by nicotine in mouse brain regions that related to the dopamine reward pathway, thus decreasing the number of cells that could react to nicotine. In addition, L-theanine treatment inhibited nicotine-induced c-Fos expression in the reward circuit related areas of the mouse brain. Knockdown of c-Fos by siRNA inhibited the excitatory status of cells but not the upregulation of TH induced by nicotine in SH-SY5Y cells. Overall, the present study showed that L-theanine reduced the nicotine-induced reward effects via inhibition of the nAChR-dopamine reward pathway. These results may offer new therapeutic strategies for treatment of tobacco addiction.

show abstract

Section: Discussionsupporting

confidence: 51%

L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway

Yan

Zhao

et al. 2012

Sci. China Life Sci.

View full text Add to dashboard Cite

show abstract

“…(c) Adaptations in nAChR function Chronic nicotine administration leads to an interesting paradoxical change in the function of nAChRs, which consists of receptor desensitization leading to receptor upregulation (Marks et al 1983;Schwartz & Kellar 1983;Changeux et al 1984;Wonnacott 1990;Flores et al 1997;Perry et al 1999;. Complex theoretical speculations have been put forth about the role of nAChR desensitization and upregulation in the subjective effects of acute nicotine and in the development and maintenance of nicotine dependence ( Marks et al 1992;Dani & Heinemann 1996;Buisson & Bertrand 2002;Quick & Lester 2002).…”

Section: Neurosubstrates Of Nicotine Reward Dependence and Withdrawalmentioning

confidence: 99%

Neurobiology of nicotine dependence

Markou

2008

Phil. Trans. R. Soc. B

236

186

View full text Add to dashboard Cite

Nicotine is a psychoactive ingredient in tobacco that significantly contributes to the harmful tobacco smoking habit. Nicotine dependence is more prevalent than dependence on any other substance. Preclinical research in animal models of the various aspects of nicotine dependence suggests a critical role of glutamate, g-aminobutyric acid (GABA), cholinergic and dopamine neurotransmitter interactions in the ventral tegmental area and possibly other brain sites, such as the central nucleus of the amygdala and the prefrontal cortex, in the effects of nicotine. Specifically, decreasing glutamate transmission or increasing GABA transmission with pharmacological manipulations decreased the rewarding effects of nicotine and cue-induced reinstatement of nicotine seeking. Furthermore, early nicotine withdrawal is characterized by decreased function of presynaptic inhibitory metabotropic glutamate 2/3 receptors and increased expression of postsynaptic glutamate receptor subunits in limbic and frontal brain sites, while protracted abstinence may be associated with increased glutamate response to stimuli associated with nicotine administration. Finally, adaptations in nicotinic acetylcholine receptor function are also involved in nicotine dependence. These neuroadaptations probably develop to counteract the decreased glutamate and cholinergic transmission that is hypothesized to characterize early nicotine withdrawal. In conclusion, glutamate, GABA and cholinergic transmission in limbic and frontal brain sites are critically involved in nicotine dependence.

show abstract

“…However, in this work, we will be focusing on the a4b2 heteromeric receptor in terms of its translational importance. In contrast to other subtypes, the a4b2 nAChR subtype has been shown to readily up-regulate following chronic exposure to nicotine, as evidenced by findings in cell culture (Xiao and Kellar 2004), rodents (Schwartz and Kellar 1983;Marks et al 1985), monkeys (Picciotto et al 2008), and humans (Mukhin et al 2008). The up-regulation of receptors in the face of increased agonist is a characteristic unique to nicotine, and its full importance is not understood.…”

Section: Neurochemisty Of Nicotinementioning

confidence: 99%

Translational Research in Nicotine Dependence

Turner

Gold

Schnoll

et al. 2013

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

Nicotine addiction accounts for 4.9 million deaths each year. Furthermore, although smoking represents a significant health burden in the United States, at present there are only three FDA-approved pharmacotherapies currently on the market: (1) nicotine replacement therapy, (2) bupropion, and (3) varenicline. Despite this obvious gap in the market, the complexity of nicotine addiction in addition to the increasing cost of drug development makes targeted drug development prohibitive. Furthermore, using combinations of mouse and human studies, additional treatments could be developed from off-the-shelf, currently approved medication lists. This article reviews translational studies targeting manipulations of the cholinergic system as a viable therapeutic target for nicotine addiction.

show abstract

Nicotinic Cholinergic Receptor Binding Sites in the Brain: Regulation in Vivo

Cited by 460 publications

References 13 publications

L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway

L-theanine inhibits nicotine-induced dependence via regulation of the nicotine acetylcholine receptor-dopamine reward pathway

Neurobiology of nicotine dependence

Translational Research in Nicotine Dependence

Contact Info

Product

Resources

About