دورية أكاديمية
Unlimited access to heroin self-administration: independent motivational markers of opiate dependence.
العنوان: | Unlimited access to heroin self-administration: independent motivational markers of opiate dependence. |
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المؤلفون: | Chen SA; Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA, USA. scott.chen@mail.nih.gov, O'Dell LE, Hoefer ME, Greenwell TN, Zorrilla EP, Koob GF |
المصدر: | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2006 Dec; Vol. 31 (12), pp. 2692-707. Date of Electronic Publication: 2006 Jan 25. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Validation Study |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8904907 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0893-133X (Print) Linking ISSN: 0893133X NLM ISO Abbreviation: Neuropsychopharmacology Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2003- : London : Nature Publishing Group Original Publication: [New York, NY] : Elsevier, [c1987- |
مواضيع طبية MeSH: | Motivation*, Brain/*drug effects , Brain/*physiopathology , Heroin/*adverse effects , Opioid-Related Disorders/*diagnosis , Opioid-Related Disorders/*physiopathology, Analgesics, Opioid/pharmacology ; Animals ; Biomarkers/analysis ; Body Weight/drug effects ; Body Weight/physiology ; Buprenorphine/pharmacology ; Circadian Rhythm/drug effects ; Circadian Rhythm/physiology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Interactions/physiology ; Eating/drug effects ; Eating/physiology ; Feeding Behavior/drug effects ; Feeding Behavior/physiology ; Injections, Intravenous ; Male ; Narcotic Antagonists/pharmacology ; Narcotics/adverse effects ; Rats ; Rats, Wistar ; Self Administration ; Substance Withdrawal Syndrome/physiopathology |
مستخلص: | The goal of the present study was to develop and validate an animal model of unlimited access to intravenous heroin self-administration combined with responding for food and water to characterize the transition to drug dependence. Male Wistar rats were allowed to lever press for heroin (60 microg/kg/0.1 ml infusion/s; fixed ratio 1; 20-s time out) and nosepoke for food and water in consecutive, daily 23-h sessions. Daily heroin intake increased over days, reaching significance by Day 14. Drug-taking increased across the circadian cycle, reflected as increases in both the nocturnal peak and diurnal nadir of heroin intake. Changes in the circadian pattern of food intake and meal patterning preceded and paralleled the changes in heroin intake. By Day 7, the circadian amplitude of feeding was blunted. Nocturnal intake decreased because rats consumed smaller and briefer meals. Diurnal intake increased due to increased meal frequency, whereas total daily food intake decreased. To control for time or experience in the self-administration boxes as a possible confound, rats with saline (no drug) tethers were tested and did not display significant changes in food intake pattern. Body weight gain slowed slightly in heroin rats relative to saline controls. Separate groups of rats revealed that significant physical dependence as measured by physical signs of opiate withdrawal following a naloxone injection (1.0 mg/kg, subcutaneous (s.c.)) was reached by Day 14. Significant increases in heroin intake could be produced using low doses of naloxone (0.003-0.03 mg/kg, s.c.) on days 28-31 of heroin access. After 6 weeks of heroin self-administration, rats injected with buprenorphine (0, 0.01, 0.04, and 0.2 mg/kg, s.c.) showed a dose-dependent reduction in heroin intake. Changes in the pattern of drug and food intake in the present unlimited heroin access model may serve as independent motivational markers for the transition to a drug-dependent state. |
التعليقات: | Erratum in: Neuropsychopharmacology. 2006 Dec;31(12):2802. |
معلومات مُعتمدة: | DA04043 United States DA NIDA NIH HHS; DK64871 United States DK NIDDK NIH HHS; F32 DA15583 United States DA NIDA NIH HHS |
المشرفين على المادة: | 0 (Analgesics, Opioid) 0 (Biomarkers) 0 (Narcotic Antagonists) 0 (Narcotics) 40D3SCR4GZ (Buprenorphine) 70D95007SX (Heroin) |
تواريخ الأحداث: | Date Created: 20060203 Date Completed: 20070105 Latest Revision: 20191210 |
رمز التحديث: | 20240628 |
DOI: | 10.1038/sj.npp.1301008 |
PMID: | 16452993 |
قاعدة البيانات: | MEDLINE |
تدمد: | 0893-133X |
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DOI: | 10.1038/sj.npp.1301008 |