ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2011
Selective α4β2 nicotinic acetylcholine receptor agonists target epigenetic mechanisms in cortical GABAergic neurons.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Nicotine-induced conditioned place preference involves dynamic changes in DNA methylation and hydroxymethylation in the zebrafish brain.Frontiers in cell and developmental biology · 2026Article
- Article
- Desformylflustrabromine, a positive allosteric modulator of α4β2-containing nicotinic acetylcholine receptors, enhances cognition in rats.Pharmacological reports : PR · 2020Article
- Choline ameliorates adult learning deficits and reverses epigenetic modification of chromatin remodeling factors related to adolescent nicotine exposure.Neurobiology of learning and memory · 2018Article
- Effects of ethanol and varenicline on female Sprague-Dawley rats in a third trimester model of fetal alcohol syndrome.Alcohol (Fayetteville, N.Y.) · 2018Article
- Cognitive Control, the Anterior Cingulate, and Nicotinic Receptors: A Case of Heterozygote Advantage.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Neurobiological Determinants of Tobacco Smoking in Schizophrenia.Frontiers in psychiatry · 2018Review
- Cholinergic Hypofunction in Presbycusis-Related Tinnitus With Cognitive Function Impairment: Emerging Hypotheses.Frontiers in aging neuroscience · 2018Article
- Alterations in the cholinergic system of brain stem neurons in a mouse model of Rett syndrome.American journal of physiology. Cell physiology · 2014Article
- Epigenetic mechanisms in schizophrenia.Dialogues in clinical neuroscience · 2014Review
- Nicotine exposure during adolescence: cognitive performance and brain gene expression in adult heterozygous reeler mice.Psychopharmacology · 2014Article
- Open label smoking cessation with varenicline is associated with decreased glutamate levels and functional changes in anterior cingulate cortex: preliminary findings.Frontiers in pharmacology · 2014Article
- Nonaggressive and adapted social cognition is controlled by the interplay between noradrenergic and nicotinic receptor mechanisms in the prefrontal cortex.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- DNA-methylation gene network dysregulation in peripheral blood lymphocytes of schizophrenia patients.Schizophrenia research · 2013Article
- The dynamics of DNA methylation in schizophrenia and related psychiatric disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Review
- Article
- Nicotine modulates multiple regions in the limbic stress network regulating activation of hypophysiotrophic neurons in hypothalamic paraventricular nucleus.Journal of neurochemistry · 2012Article
- Varenicline is a potent partial agonist at α6β2* nicotinic acetylcholine receptors in rat and monkey striatum.The Journal of pharmacology and experimental therapeutics · 2012Article
- Positive and negative effects of alcohol and nicotine and their interactions: a mechanistic review.Neurotoxicity research · 2012Review
- A neurochemical basis for an epigenetic vision of psychiatric disorders (1994-2009).Pharmacological research · 2011Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Nicotine improves cognitive performance and attention in both experimental animals and in human subjects, including patients affected by neuropsychiatric disorders. However, the specific molecular mechanisms underlying nicotine-induced behavioral changes remain unclear. We have recently shown in mice that repeated injections of nicotine, which achieve plasma concentrations comparable to those reported in high cigarette smokers, result in an epigenetically induced increase of glutamic acid decarboxylase 67 (GAD(67)) expression. Here we explored the impact of synthetic α(4)β(2) and α(7) nAChR agonists on GABAergic epigenetic parameters. Varenicline (VAR), a high-affinity partial agonist at α(4)β(2) and a lower affinity full agonist at α(7) neuronal nAChR, injected in doses of 1-5 mg/kg/s.c. twice daily for 5 days, elicited a 30-40% decrease of cortical DNA methyltransferase (DNMT)1 mRNA and an increased expression of GAD(67) mRNA and protein. This upregulation of GAD(67) was abolished by the nAChR antagonist mecamylamine. Furthermore, the level of MeCP(2) binding to GAD(67) promoters was significantly reduced following VAR administration. This effect was abolished when VAR was administered with mecamylamine. Similar effects on cortical DNMT1 and GAD(67) expression were obtained after administration of A-85380, an agonist that binds to α(4)β(2) but has negligible affinity for α(3)β(4) or α(7) subtypes containing nAChR. In contrast, PNU-282987, an agonist of the homomeric α(7) nAChR, failed to decrease cortical DNMT1 mRNA or to induce GAD(67) expression. The present study suggests that the α(4)β(2) nAChR agonists may be better suited to control the epigenetic alterations of GABAergic neurons in schizophrenia than the α(7) nAChR agonists.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.