ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Knockdown of hypocretin attenuates extended access of cocaine self-administration in rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 44 citations in OpenAlex.
- Hypocretin signaling in the central amygdala drives methamphetamine self-administration in male rats.Neuropharmacology · 2025Article
- Melanin-Concentrating Hormone (MCH): Role in Mediating Reward-Motivated and Emotional Behavior and the Behavioral Disturbances Produced by Repeated Exposure to Reward Substances.International journal of molecular sciences · 2025Review
- Exploring the Toxicity and Therapeutic Potential ofInternational journal of molecular sciences · 2025Article
- Abuse potential assessment of the dual orexin receptor antagonist daridorexant in rats.Journal of psychopharmacology (Oxford, England) · 2023Article
- Subpopulations of hypocretin/orexin neurons differ in measures of their cell proliferation, dynorphin co-expression, projections, and response to embryonic ethanol exposure.Scientific reports · 2023Article
- Orexin Reserve: A Mechanistic Framework for the Role of Orexins (Hypocretins) in Addiction.Biological psychiatry · 2022Review
- Suvorexant maintenance enhances the reinforcing but not subjective and physiological effects of intravenous cocaine in humans.Pharmacology, biochemistry, and behavior · 2022Article
- Effects of single and dual hypocretin-receptor blockade or knockdown of hypocretin projections to the central amygdala on alcohol drinking in dependent male rats.Addiction neuroscience · 2022Article
- Orexin-1 receptor signaling in ventral tegmental area mediates cue-driven demand for cocaine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Predictive and motivational factors influencing anticipatory contrast: A comparison of contextual and gustatory predictors in food restricted and free-fed rats.Physiology & behavior · 2021Article
- Article
- The orexin (hypocretin) neuropeptide system is a target for novel therapeutics to treat cocaine use disorder with alcohol coabuse.Neuropharmacology · 2021Review
- Sex Differences in Demand for Highly Palatable Foods: Role of the Orexin System.The international journal of neuropsychopharmacology · 2021Article
- Sex- and Brain Region-specific Changes in Gene Expression in Male and Female Rats as Consequences of Methamphetamine Self-administration and Abstinence.Neuroscience · 2021Article
- Understanding the Role of Orexin Neuropeptides in Drug Addiction: Preclinical Studies and Translational Value.Frontiers in behavioral neuroscience · 2021Review
- Targeting the Orexin System for Prescription Opioid Use Disorder.Brain sciences · 2020Review
- Cocaine abuse and midbrain circuits: Functional anatomy of hypocretin/orexin transmission and therapeutic prospect.Brain research · 2020Review
- The orexin-1 receptor antagonist SB-334867 reduces motivation, but not inhibitory control, in a rat stop signal task.Brain research · 2020Article
- Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking.The international journal of neuropsychopharmacology · 2019Article
- Activation of lateral hypothalamic group III metabotropic glutamate receptors suppresses cocaine-seeking following abstinence and normalizes drug-associated increases in excitatory drive to orexin/hypocretin cells.Neuropharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The hypocretin/orexin (HCRT) neuropeptide system regulates feeding, arousal state, stress responses, and reward, especially under conditions of enhanced motivational relevance. In particular, HCRT neurotransmission facilitates drug-seeking behavior in circumstances that demand increased effort and/or motivation to take the drug. The present study used a shRNA-encoding adeno-associated viral vector to knockdown Hcrt expression throughout the dorsal hypothalamus in adult rats and determine the role of HCRT in cocaine self-administration. Chronic Hcrt silencing did not impact cocaine self-administration under short-access conditions, but robustly attenuated cocaine intake under extended access conditions, a model that mimics key features of compulsive cocaine taking. In addition, Hcrt silencing decreased motivation for both cocaine and a highly palatable food reward (i.e., sweetened condensed milk; SCM) under a progressive ratio schedule of reinforcement, but did not alter responding for SCM under a fixed ratio schedule. Importantly, Hcrt silencing did not affect food or water consumption, and had no consequence for general measures of arousal and stress reactivity. At the molecular level, chronic Hcrt knockdown reduced the number of neurons expressing dynorphin (DYN), and to a smaller extent melanin-concentrating hormone (MCH), in the dorsal hypothalamus. These original findings support the hypothesis that HCRT neurotransmission promotes operant responding for both drug and non-drug rewards, preferentially under conditions requiring a high degree of motivation. Furthermore, the current study provides compelling evidence for the involvement of the HCRT system in cocaine self-administration also under low-effort conditions in rats allowed extended access, possibly via functional interactions with DYN and MCH signaling.
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.