ArticlePsychopharmacology2013
Interactions between VTA orexin and glutamate in cue-induced reinstatement of cocaine seeking in rats.
Article in Psychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 146 citations in OpenAlex.
- Hypocretin receptor 1 blockade early in abstinence prevents incubation of cocaine seeking and normalizes dopamine transmission.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Fos expression in the periaqueductal gray, but not the ventromedial hypothalamus, is correlated with psychosocial stress-induced cocaine-seeking behavior in rats.Addiction neuroscience · 2025Article
- Emerging medications and pharmacological treatment approaches for substance use disorders.Pharmacology, biochemistry, and behavior · 2025Review
- Dorsal hippocampus to nucleus accumbens projections drive reinforcement via activation of accumbal dynorphin neurons.Nature communications · 2024Article
- Hypocretin / Orexin Receptor 1 Knockdown in GABA or Dopamine Neurons in the Ventral Tegmental Area Differentially Impact Mesolimbic Dopamine and Motivation for Cocaine.Addiction neuroscience · 2023Article
- Pharmacological activation of the amygdala, but not single prolonged footshock-induced acute stress, interferes with cue-induced motivation toward food rewards in rats.Frontiers in behavioral neuroscience · 2023Article
- Orexin Reserve: A Mechanistic Framework for the Role of Orexins (Hypocretins) in Addiction.Biological psychiatry · 2022Review
- Habitual behaviour associated with exposure to high-calorie diet is prevented by an orexin-receptor-1 antagonist.Addiction neuroscience · 2022Article
- Optogenetic stimulation of Kiss1Frontiers in endocrinology · 2022Article
- Prelimbic cortical projections to rostromedial tegmental nucleus play a suppressive role in cue-induced reinstatement of cocaine seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Age-specific treatment effects of orexin/hypocretin-receptor antagonism on methamphetamine-seeking behavior.Drug and alcohol dependence · 2021Article
- Extinction vs. Abstinence: A Review of the Molecular and Circuit Consequences of Different Post-Cocaine Experiences.International journal of molecular sciences · 2021Review
- Ventral Pallidum GABA Neurons Mediate Motivation Underlying Risky Choice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Intermittent self-administration of fentanyl induces a multifaceted addiction state associated with persistent changes in the orexin system.Addiction biology · 2021Article
- The number of lateral hypothalamus orexin/hypocretin neurons contributes to individual differences in cocaine demand.Addiction biology · 2020Article
- Persistent effects of the orexin-1 receptor antagonist SB-334867 on motivation for the fast acting opioid remifentanil.Brain research · 2020Article
- The orexin-1 receptor antagonist SB-334867 reduces motivation, but not inhibitory control, in a rat stop signal task.Brain research · 2020Article
- Cell type- and pathway-specific synaptic regulation of orexin neurocircuitry.Brain research · 2020Review
- Targeting the orexin system for prescription opioid use disorder: Orexin-1 receptor blockade prevents oxycodone taking and seeking in rats.Neuropharmacology · 2020Article
- Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation.Psychopharmacology · 2020Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
rationaleGlutamate and orexin/hypocretin systems are involved in Pavlovian cue-triggered drug seeking.
objectivesHere, we asked whether orexin and glutamate interact within ventral tegmental area (VTA) to promote reinstatement of extinguished cocaine seeking in a rat self-administration paradigm. METHODS/
resultsWe first found that bilateral VTA microinjections of the orexin 1 receptor (OX1R) antagonist SB-334867 (SB) or a cocktail of the AMPA and NMDA glutamate receptor antagonists CNQX/AP-5 reduced reinstatement of cocaine seeking elicited by cues. In contrast, neither of these microinjections nor systemic SB reduced cocaine-primed reinstatement. Additionally, unilateral VTA OX1R blockade combined with contralateral VTA glutamate blockade attenuated cue-induced reinstatement, indicating that VTA orexin and glutamate are simultaneously necessary for cue-induced reinstatement. We further probed the receptor specificity of glutamate actions in VTA, finding that CNQX, but not AP-5, dose-dependently attenuated cue-induced reinstatement, indicating that AMPA but not NMDA receptor transmission is required for this type of cocaine seeking. Given the necessary roles of both OX1 and AMPA receptors in VTA for cue-induced cocaine seeking, we hypothesized that these signaling pathways interact during this behavior. We found that PEPA, a positive allosteric modulator of AMPA receptors, completely reversed the SB-induced attenuation of reinstatement behavior. Intra-VTA PEPA alone did not alter cue-induced reinstatement, indicating that potentiating AMPA activity with this drug specifically compensates for OX1R blockade, rather than simply inducing or enhancing reinstatement itself.
conclusionsThese findings show that cue-induced, but not cocaine-primed, reinstatement of cocaine seeking is dependent upon orexin and AMPA receptor interactions in VTA.
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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.