ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2009
NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 151 citations in OpenAlex.
- High- and low-dose topiramate for the treatment of persons with alcohol use disorder who smoke cigarettes: A randomized control trial.Alcohol, clinical & experimental research · 2025Trial
- Topiramate decreases the salience of motivationally relevant visual cues among smokers with alcohol use disorder.Alcoholism, clinical and experimental research · 2022Trial
- A double-blind, placebo-controlled trial of the NMDA glycine site antagonist, GW468816, for prevention of relapse to smoking in females.Journal of clinical psychopharmacology · 2011Trial
- A role for glutamate in subjective response to smoking and its action on inhibitory control.Psychopharmacology · 2011Trial
- The role of cystine-glutamate exchange in nicotine dependence in rats and humans.Biological psychiatry · 2009Trial
- Disruption ofiScience · 2026Article
- Changes in Locomotor Activity Observed During Acute Nicotine Withdrawal Can Be Attenuated by Ghrelin and GHRP-6 in Rats.Biomedicines · 2025Article
- Impact of Serine Racemase Deletion on Nicotine Discrimination.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Multimodal 7T imaging reveals enhanced functional coupling between salience and frontoparietal networks in young adult tobacco cigarette smokers.Brain imaging and behavior · 2024Article
- SR9883 is a novel small-molecule enhancer of α4β2* nicotinic acetylcholine receptor signaling that decreases intravenous nicotine self-administration in rats.Frontiers in molecular neuroscience · 2024Article
- Ghrelin Amplifies the Nicotine-Induced Release of Dopamine in the Bed Nucleus of Stria Terminalis (BNST).Biomedicines · 2023Article
- Altered neuronal activity in the ventromedial prefrontal cortex drives nicotine intake escalation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation.Biomedicines · 2023Review
- Article
- The effect of CNQX on self-administration: present in nicotine, absent in methamphetamine model.Frontiers in behavioral neuroscience · 2023Article
- Allosteric Modulators of Metabotropic Glutamate Receptors as Novel Therapeutics for Neuropsychiatric Disease.Pharmacological reviews · 2022Review
- Effects of NMDA receptor antagonists on behavioral economic indices of cocaine self-administration.Drug and alcohol dependence · 2022Article
- Epigenetic Mechanisms Mediate Nicotine-Induced Reward and Behaviour in Zebrafish.Current neuropharmacology · 2022Article
- JQ1 attenuates psychostimulant- but not opioid-induced conditioned place preference.Behavioural brain research · 2022Article
- Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation.Frontiers in neuroscience · 2022Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug.
Indexed as
Identifiers
What OpenQuestion holds
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.