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Self-Administration of Fentanyl-Alprazolam Combinations by Rhesus Monkeys Responding under a Progressive-Ratio Schedule.

التفاصيل البيبلوغرافية
العنوان: Self-Administration of Fentanyl-Alprazolam Combinations by Rhesus Monkeys Responding under a Progressive-Ratio Schedule.
المؤلفون: Berro LF; Department of Psychiatry & Human Behavior, Center for Innovation & Discovery in Addictions, University of Mississippi Medical Center, 2500 N State Street, Jackson, Mississippi lberro@umc.edu., Zamarripa CA; Department of Psychiatry & Human Behavior, Center for Innovation & Discovery in Addictions, University of Mississippi Medical Center, 2500 N State Street, Jackson, Mississippi., Rowlett JK; Department of Psychiatry & Human Behavior, Center for Innovation & Discovery in Addictions, University of Mississippi Medical Center, 2500 N State Street, Jackson, Mississippi.
المصدر: The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2022 Dec; Vol. 383 (3), pp. 199-207. Date of Electronic Publication: 2022 Sep 24.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 0376362 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-0103 (Electronic) Linking ISSN: 00223565 NLM ISO Abbreviation: J Pharmacol Exp Ther Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Bethesda, MD : American Society for Pharmacology and Experimental Therapeutics
Original Publication: Baltimore : Williams & Wilkins
مواضيع طبية MeSH: Substance-Related Disorders* , Cocaine*/pharmacology, Animals ; Male ; Female ; Fentanyl/pharmacology ; Macaca mulatta ; Analgesics, Opioid/pharmacology ; Alprazolam/pharmacology ; Dose-Response Relationship, Drug ; Self Administration ; Benzodiazepines ; Reinforcement Schedule
مستخلص: This study evaluated the reinforcing effects of fentanyl, alone or in combination with the benzodiazepine alprazolam, in rhesus monkeys (3 females, 3 males). Subjects were trained to self-administer the opioid remifentanil (0.3 µ g/kg/injection) under a progressive-ratio schedule of reinforcement. The reinforcing effects of fentanyl (0.1-10 µ g/kg/injection) or alprazolam (1.0-100 µ g/kg/injection) alone, or in combinations of fixed proportions (1:1, 1:3, and 3:1 fentanyl:alprazolam, with 1:1 based on the potencies of drugs alone) were evaluated in single-day test sessions (with double determinations). Dose-equivalence analysis was used to determine the extent to which fentanyl and alprazolam combinations differed from additivity. Fentanyl functioned as a positive reinforcer in all monkeys, while alprazolam was a reinforcer in 3 of 6 monkeys only. Therefore, drug combination data were grouped as "alprazolam-taking" and "non-alprazolam-taking" monkeys. For alprazolam-taking monkeys, we observed additive effects for the 3:1 and 1:3 combinations, and a significant supra-additive interaction for the 1:1 combination of fentanyl and alprazolam. For 2 of the 3 non-alprazolam-taking monkeys, the combination of fentanyl and alprazolam resulted in enhanced reinforcing effects relative to either drug alone. However, the one monkey showed primarily inhibitory, or suppressive effects, with the 3:1 dose combination resulting in a relatively modest rightward shift in the fentanyl dose-response function. In summary, our findings show that combining fentanyl and alprazolam generally result in proportion-dependent additive or supra-additive enhancements. These data raise the possibility that the prevalence of opioid-benzodiazepine polydrug abuse may reflect a unique enhancement of these drugs' reinforcing effects, although individual differences may exist. SIGNIFICANCE STATEMENT: Addressing the critical question of the degree to which benzodiazepines can modulate the abuse-related effects of opioids may provide improved pathways to treatment of this common form of polydrug addiction. In the present study, we show that combinations of the opioid fentanyl and the benzodiazepine alprazolam can be more reinforcing than either drug alone in a rhesus monkey model, suggesting that enhancement of reinforcement processes may underlie this prevalent form of polydrug use disorder.
(Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)
References: J Pharmacol Exp Ther. 1997 Dec;283(3):1119-29. (PMID: 9399984)
Pharmacol Biochem Behav. 2005 Jul;81(3):657-63. (PMID: 15961147)
Addict Behav. 2018 Dec;87:24-32. (PMID: 29940388)
Addict Behav. 2019 Jan;88:48-55. (PMID: 30142484)
J Addict Med. 2018 Jan/Feb;12(1):4-10. (PMID: 28777203)
Pharmacotherapy. 2004 Sep;24(9):1177-85. (PMID: 15460178)
Drug Alcohol Depend. 2012 Sep 1;125(1-2):8-18. (PMID: 22857878)
Expert Opin Drug Saf. 2010 Mar;9(2):355-64. (PMID: 20175702)
J Psychosoc Nurs Ment Health Serv. 2018 May 1;56(6):11-15. (PMID: 29873801)
Neuropsychopharmacology. 2013 May;38(6):1006-14. (PMID: 23303046)
J Pharmacol Exp Ther. 2004 Sep;310(3):981-6. (PMID: 15175417)
Psychopharmacology (Berl). 2008 Jun;198(3):387-94. (PMID: 18461311)
Psychopharmacology (Berl). 2008 Mar;196(4):575-82. (PMID: 18026937)
J Pharmacol Exp Ther. 2011 Jun;337(3):805-11. (PMID: 21411495)
Drug Alcohol Depend. 2018 Apr 1;185:10-16. (PMID: 29413433)
Psychopharmacology (Berl). 1985;87(2):225-32. (PMID: 3931151)
J Pharmacol Exp Ther. 2006 Oct;319(1):1-7. (PMID: 16670349)
Anaesth Intensive Care. 1987 Aug;15(3):330-1. (PMID: 3661967)
J Addict Dis. 2008;27(3):37-48. (PMID: 18956528)
MMWR Surveill Summ. 2015 Oct 16;64(9):1-14. (PMID: 26469747)
J Pharmacol Exp Ther. 2017 Jul;362(1):59-66. (PMID: 28438777)
Drug Alcohol Depend. 2009 Jan 1;99(1-3):338-44. (PMID: 18824311)
Br J Clin Pharmacol. 1981;11 Suppl 1:99S-104S. (PMID: 6133541)
Psychopharmacology (Berl). 1996 Jun;125(4):361-70. (PMID: 8826541)
Life Sci. 1983 Mar 7;32(10):1043-51. (PMID: 6338330)
Trends Neurosci. 2011 Apr;34(4):188-97. (PMID: 21353710)
J Neurosci. 2000 Jun 15;20(12):4555-62. (PMID: 10844025)
Addict Behav. 2019 Oct;97:14-19. (PMID: 31112911)
Brain Res. 1998 Jul 6;798(1-2):156-65. (PMID: 9666112)
Pharmacol Biochem Behav. 2005 Nov;82(3):470-7. (PMID: 16297973)
Drug Alcohol Depend. 2005 May 9;78(2):113-23. (PMID: 15845314)
Pharmacol Biochem Behav. 2003 Apr;75(1):75-80. (PMID: 12759115)
Forensic Sci Int. 2018 Aug;289:207-214. (PMID: 29902699)
Curr Protoc Pharmacol. 2011 Dec;Chapter 10:Unit10.5. (PMID: 22382996)
J Subst Abuse Treat. 2016 Sep;68:57-61. (PMID: 27431047)
JAMA Intern Med. 2017 Feb 1;177(2):274-275. (PMID: 27942726)
MMWR Morb Mortal Wkly Rep. 2021 Aug 27;70(34):1136-1141. (PMID: 34437522)
Eur J Anaesthesiol. 2001 Dec;18(12):789-97. (PMID: 11737177)
Addict Behav. 2017 Feb;65:283-288. (PMID: 27575980)
Psychopharmacologia. 1975 Jul 23;43(1):81-3. (PMID: 1161995)
Life Sci. 1978 Mar;22(10):897-906. (PMID: 642704)
J Clin Pharmacol. 2005 May;45(5):529-37. (PMID: 15831776)
Psychopharmacology (Berl). 2018 Aug;235(8):2245-2256. (PMID: 29785554)
Psychopharmacology (Berl). 1997 Oct;133(4):363-71. (PMID: 9372536)
Drug Alcohol Depend. 2020 May 25;213:108076. (PMID: 32474260)
J Neurosci. 1996 Apr 15;16(8):2684-92. (PMID: 8786444)
J Pharmacol Exp Ther. 2007 Jun;321(3):1135-43. (PMID: 17351103)
Subst Use Misuse. 2020;55(6):861-870. (PMID: 31900021)
Genes Cancer. 2011 Nov;2(11):1003-8. (PMID: 22737266)
N Engl J Med. 2016 Jan 28;374(4):363-71. (PMID: 26816013)
معلومات مُعتمدة: F31 DA048586 United States DA NIDA NIH HHS; R01 DA011792 United States DA NIDA NIH HHS; R00 DA049886 United States DA NIDA NIH HHS; K99 DA049886 United States DA NIDA NIH HHS; R21 DA046778 United States DA NIDA NIH HHS; R01 DA043204 United States DA NIDA NIH HHS
المشرفين على المادة: UF599785JZ (Fentanyl)
0 (Analgesics, Opioid)
YU55MQ3IZY (Alprazolam)
12794-10-4 (Benzodiazepines)
I5Y540LHVR (Cocaine)
تواريخ الأحداث: Date Created: 20220924 Date Completed: 20221115 Latest Revision: 20231202
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9667979
DOI: 10.1124/jpet.122.001191
PMID: 36153004
قاعدة البيانات: MEDLINE
الوصف
تدمد:1521-0103
DOI:10.1124/jpet.122.001191