ArticlePsychopharmacology2004
Effects of extended access to high versus low cocaine doses on self-administration, cocaine-induced reinstatement and brain mRNA levels in rats.
Article in Psychopharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed.
- Increased drug seeking and vulnerability to relapse after escalation of nicotine intake by dose manipulation in male and female rats.Psychopharmacology · 2026Article
- Escalated Oxycodone Self-Administration Is Associated with Activation of Specific Gene Networks in the Rat Dorsal Striatum.International journal of molecular sciences · 2025Article
- Similarities and Differences in Diagnostic Criteria.Advances in experimental medicine and biology · 2025Review
- The ventral tegmental area dopamine to basolateral amygdala projection supports acquisition of cocaine self-administration.Neuropharmacology · 2024Article
- The mGlu5 receptor negative allosteric modulator mavoglurant reduces escalated cocaine self-administration in male and female rats.Psychopharmacology · 2024Article
- Article
- Voltage-gated potassium channels control extended access cocaine seeking: a role for nucleus accumbens astrocytes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Altered neuronal activity in the ventromedial prefrontal cortex drives nicotine intake escalation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- PPL-103: A mixed opioid partial agonist with desirable anti-cocaine properties.Progress in neuro-psychopharmacology & biological psychiatry · 2022Article
- Dopamine D2 receptors bidirectionally regulate striatal enkephalin expression: Implications for cocaine reward.Cell reports · 2022Article
- Aerobic exercise as a promising nonpharmacological therapy for the treatment of substance use disorders.Journal of neuroscience research · 2022Review
- The role of enkephalinergic systems in substance use disorders.Frontiers in systems neuroscience · 2022Review
- Neuroadaptations and TGF-β signaling: emerging role in models of neuropsychiatric disorders.Molecular psychiatry · 2022Review
- Sex- and Dose-Dependent Differences in the Development of an Addiction-Like Phenotype Following Extended-Access Fentanyl Self-Administration.Frontiers in pharmacology · 2022Article
- Animal Models of the Behavioral Symptoms of Substance Use Disorders.Cold Spring Harbor perspectives in medicine · 2021Review
- Escalation and reinstatement of fentanyl self-administration in male and female rats.Psychopharmacology · 2021Article
- An optimized procedure for robust volitional cocaine intake in mice.Experimental and clinical psychopharmacology · 2021Article
- Dopamine 'ups and downs' in addiction revisited.Trends in neurosciences · 2021Review
- Alpha-pyrrolidinopentiophenone and mephedrone self-administration produce differential neurochemical changes following short- or long-access conditions in rats.European journal of pharmacology · 2021Article
- Neuronal activity associated with cocaine preference: Effects of differential cocaine intake.Neuropharmacology · 2021Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
Abstract
rationaleThe investigation of rodent cocaine self-administration (SA) under conditions that promote escalating patterns of intake may provide insight into the loss of control over drug use that is central to human addiction.
objectiveThis study examines the effects of daily long-access (LgA) SA of high or low cocaine doses on drug intake, extinction, reinstatement, and brain mRNA levels.
methodsThree groups of male Sprague-Dawley rats were trained to self-administer cocaine during multiple-dose sessions. Short-access (ShA) rats were tested daily for multi-dose SA then remained in the chambers for 7 h with no cocaine available. LgA rats had access to low (0.5 mg/kg per infusion; LgA-LD) or high (2.0 mg/kg per infusion; LgA-HD) cocaine doses for 7 h after multi-dose SA. After 14 days, responding was extinguished, cocaine-induced reinstatement was determined, and preproenkephalin (ppENK), preprodynorphin (ppDYN), corticotropin releasing factor (CRF) and dopamine D(2) receptor (D(2)R) mRNA levels were measured in various brain regions using a quantitative solution hybridization RNase protection assay.
resultsWhereas SA was not altered in ShA rats and only increased during the "loading phase" in LgA-LD rats, a general escalation of intake was found in LgA-HD rats. LgA, particularly LgA-HD, rats were more susceptible to reinstatement than ShA rats. Caudate-putamen ppENK and nucleus accumbens D(2)R mRNA levels were elevated in LgA-HD rats. Overall, D(2)R mRNA levels were positively correlated with reinstatement.
conclusionsThe escalation of cocaine SA under LgA conditions is dose-dependent and is associated with heightened susceptibility to drug-induced relapse. The characterization of neurobiological alterations that accompany escalated SA should facilitate the identification of mechanisms underlying the onset of human addiction.
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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.