ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Cognitive rigidity and BDNF-mediated frontostriatal glutamate neuroadaptations during spontaneous nicotine withdrawal.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 12 citations in OpenAlex.
- Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020-2025).Frontiers in molecular neuroscience · 2026Pooled it
- Distinct patterns of prefrontal cortical disengagement during inhibitory control in addiction: A meta-analysis based on population characteristics.Neuroscience and biobehavioral reviews · 2021Pooled it
- A Preliminary Study of Smoking Abstinence Effects on Acquisition and Reversal Learning in a Probabilistic Learning Task.Substance use & misuse · 2026Trial
- Altered Regional Brain Activity Underlying the Higher Postoperative Analgesic Requirements in Abstinent Smokers: A Prospective Cohort Study.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Interactive effect of BDNF rs10835210 polymorphism and childhood maltreatment on cognitive functioning in Chinese male patients with methamphetamine use disorder.European archives of psychiatry and clinical neuroscience · 2025Article
- Convergent actions of stress and stimulants via epigenetic regulation of neural circuitry.Trends in neurosciences · 2022Review
- Nitric Oxide Linked to mGluR5 Upregulates BDNF Synthesis by Activating MMP2 in the Caudate and Putamen after Challenge Exposure to Nicotine in Rats.International journal of molecular sciences · 2022Article
- Ebselen prevents cigarette smoke-induced cognitive dysfunction in mice by preserving hippocampal synaptophysin expression.Journal of neuroinflammation · 2022Article
- Multidimensional Intersection of Nicotine, Gene Expression, and Behavior.Frontiers in behavioral neuroscience · 2021Article
- Glial cells as therapeutic targets for smoking cessation.Neuropharmacology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cognitive flexibility is the ability to switch strategic responses adaptively in changing environments. Cognitive rigidity imposed by neural circuit adaptations during nicotine abstinence may foster maladaptive nicotine taking in addicts. We systematically examined the effects of spontaneous withdrawal in mice exposed to either nicotine (6.3 or 18 mg/kg/day) or saline for 14 days on cognitive flexibility using an operant strategy set-shifting task. Because frontostriatal circuits are critical for cognitive flexibility and brain-derived neurotrophic factor (BDNF) modulates glutamate plasticity in these circuits, we also explored the effects of nicotine withdrawal on these neurochemical substrates. Mice undergoing nicotine withdrawal required more trials to attain strategy-switching criterion. Error analysis show that animals withdrawn from both nicotine doses committed higher perseverative errors, which correlated with measures of anxiety. However, animals treated with the higher nicotine dose also displayed more strategy maintenance errors that remained independent of negative affect. BDNF mRNA expression increased in the medial prefrontal cortex (mPFC) following nicotine withdrawal. Surprisingly, BDNF protein declined in mPFC but was elevated in dorsal striatum (DS). DS BDNF protein positively correlated with perseverative and maintenance errors, suggesting mPFC-DS overflow of BDNF during withdrawal. BDNF-evoked glutamate release and synapsin phosphorylation was attenuated within DS synapses, but enhanced in the nucleus accumbens, suggesting a dichotomous role of BDNF signaling in striatal regions. Taken together, these data suggest that spontaneous nicotine withdrawal impairs distinct components of cognitive set-shifting and these deficits may be linked to BDNF-mediated alterations in glutamate signaling dynamics in discrete frontostriatal circuits.
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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.