ArticleNature medicine2017
Nicotine reverses hypofrontality in animal models of addiction and schizophrenia.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 5 of them syntheses that pooled it.
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Who cites it
97 citing papers in PubMed, 5 syntheses or guidelines pooled it, 184 citations in OpenAlex.
- Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals.Drug and alcohol dependence · 2024Pooled it
- A systematic review of digital interventions for smoking cessation in patients with serious mental illness.Psychological medicine · 2023Pooled it
- Neuromodulation to Treat Substance Use Disorders in People With Schizophrenia and Other Psychoses: A Systematic Review.Frontiers in psychiatry · 2022Pooled it
- Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews.BMC medicine · 2021Pooled it
- Polygenic liability for schizophrenia predicts shifting-specific executive function deficits and tobacco use in a moderate drinking community sample.Psychiatry research · 2019Pooled it
- One-day tropisetron treatment improves cognitive deficits and P50 inhibition deficits in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Trial
- Sex-Dependent Alterations in Behavioral Development of Mice Lacking α5-Nicotinic Acetylcholine Receptors.Journal of neuroscience research · 2026Article
- A specific basal forebrain-medial prefrontal cholinergic pathway improves attentional control in male mice.Scientific reports · 2026Article
- The alpha7 nicotinic acetylcholine receptor mediates network dysfunction in a mouse model of local amyloid pathology.Molecular psychiatry · 2026Article
- Disorganized Inhibitory Dynamics in Hippocampal area CA1 of 22q11.2 Deletion Mutant Mice.bioRxiv : the preprint server for biology · 2026Article
- A new framework for nicotinic receptor-targeted therapeutic strategies in psychiatric and neurodegenerative disorders.Frontiers in cellular neuroscience · 2026Article
- α5-containing nicotinic acetylcholine receptors regulate state transitions in cortical networks and modulate susceptibility to epileptiform discharges.Frontiers in neural circuits · 2026Article
- Rhythmic network activity in human brain slices: variability, mechanisms, and translational insights.Frontiers in synaptic neuroscience · 2026Review
- The influence of CHRNA5 and D398N missense variation on social and emotional behaviors in rodents and humans.Translational psychiatry · 2025Article
- Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks.Molecular psychiatry · 2025Review
- A multi-level exploration of the genetic basis between lung cancer and schizophrenia.Annals of general psychiatry · 2025Article
- Semantic Processing Deficits and Their Use as Early Biomarkers in Schizophrenia.Healthcare (Basel, Switzerland) · 2025Article
- Transient Inhibition of the Mediodorsal Thalamus During Early Adolescence Induces Hypofrontality and Social Memory Deficits in Young Adulthood.Biological psychiatry global open science · 2025Article
- Tobacco Smoking Functional Networks: A Whole-Brain Connectome Analysis in 24 539 Individuals.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2025Article
- Association between autoimmune disease and neurodevelopmental disorder: a Mendelian randomization analysis.Italian journal of pediatrics · 2025Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
The prefrontal cortex (PFC) underlies higher cognitive processes that are modulated by nicotinic acetylcholine receptor (nAChR) activation by cholinergic inputs. PFC spontaneous default activity is altered in neuropsychiatric disorders, including schizophrenia-a disorder that can be accompanied by heavy smoking. Recently, genome-wide association studies (GWAS) identified single-nucleotide polymorphisms (SNPs) in the human CHRNA5 gene, encoding the α5 nAChR subunit, that increase the risks for both smoking and schizophrenia. Mice with altered nAChR gene function exhibit PFC-dependent behavioral deficits, but it is unknown how the corresponding human polymorphisms alter the cellular and circuit mechanisms underlying behavior. Here we show that mice expressing a human α5 SNP exhibit neurocognitive behavioral deficits in social interaction and sensorimotor gating tasks. Two-photon calcium imaging in awake mouse models showed that nicotine can differentially influence PFC pyramidal cell activity by nAChR modulation of layer II/III hierarchical inhibitory circuits. In α5-SNP-expressing and α5-knockout mice, lower activity of vasoactive intestinal polypeptide (VIP) interneurons resulted in an increased somatostatin (SOM) interneuron inhibitory drive over layer II/III pyramidal neurons. The decreased activity observed in α5-SNP-expressing mice resembles the hypofrontality observed in patients with psychiatric disorders, including schizophrenia and addiction. Chronic nicotine administration reversed this hypofrontality, suggesting that administration of nicotine may represent a therapeutic strategy for the treatment of schizophrenia, and a physiological basis for the tendency of patients with schizophrenia to self-medicate by smoking.
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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.