A comparison of the reinforcing strength of cocaethylene and cocaine in monkeys responding under progressive-ratio and concurrent choice schedules of reinforcement.
Cocaethylene
Cocaine
Monkey
Reinforcing strength
Self-administration
Journal
Drug and alcohol dependence
ISSN: 1879-0046
Titre abrégé: Drug Alcohol Depend
Pays: Ireland
ID NLM: 7513587
Informations de publication
Date de publication:
01 10 2023
01 10 2023
Historique:
received:
13
06
2023
revised:
24
08
2023
accepted:
24
08
2023
pmc-release:
01
10
2024
medline:
4
10
2023
pubmed:
13
9
2023
entrez:
12
9
2023
Statut:
ppublish
Résumé
Individuals who use cocaine have high rates of co-morbid alcohol use and when ethanol and cocaine are administered concurrently, the metabolite cocaethylene is formed. Cocaethylene is equipotent to cocaine in blocking dopamine reuptake and substitutes for cocaine in drug discrimination studies. However, no previous work has directly compared the reinforcing strength of cocaine to cocaethylene. In Experiment 1, three individually-housed adult male rhesus macaques self-administer cocaine under a progressive-ratio (PR) schedule of reinforcement, during daily 4-hr sessions. Under this schedule, the primary dependent variable is the number of injections received, or the break point (BP). Saline, cocaine (0.001-0.3mg/kg/injection) and cocaethylene (0.0003-0.1mg/kg/injection) dose-response curves were determined. In Experiment 2, two female cynomolgus and one rhesus macaque responded under a concurrent schedule of drug (cocaine or cocaethylene) vs. 1.0-g banana-flavored food pellets, during daily 1-hr sessions. Both cocaine and cocaethylene functioned as reinforcers under the PR and concurrent choice schedules of reinforcement. Under the PR schedule, peak BPs were not significantly different, nor were ED50 values on the ascending limb, suggesting that cocaethylene has equal reinforcing strength and potency to cocaine. Under the concurrent drug-food choice procedure, cocaethylene was also equally potent to cocaine. Under two schedules of reinforcement designed to assess reinforcing strength, cocaethylene and cocaine were equipotent and of equal reinforcing strength. Because cocaethylene has a longer duration of action, it is important for studies designed to evaluate treatments for cocaine use to also consider the effects of these interventions on cocaethylene.
Sections du résumé
BACKGROUND
Individuals who use cocaine have high rates of co-morbid alcohol use and when ethanol and cocaine are administered concurrently, the metabolite cocaethylene is formed. Cocaethylene is equipotent to cocaine in blocking dopamine reuptake and substitutes for cocaine in drug discrimination studies. However, no previous work has directly compared the reinforcing strength of cocaine to cocaethylene.
METHODS
In Experiment 1, three individually-housed adult male rhesus macaques self-administer cocaine under a progressive-ratio (PR) schedule of reinforcement, during daily 4-hr sessions. Under this schedule, the primary dependent variable is the number of injections received, or the break point (BP). Saline, cocaine (0.001-0.3mg/kg/injection) and cocaethylene (0.0003-0.1mg/kg/injection) dose-response curves were determined. In Experiment 2, two female cynomolgus and one rhesus macaque responded under a concurrent schedule of drug (cocaine or cocaethylene) vs. 1.0-g banana-flavored food pellets, during daily 1-hr sessions.
RESULTS
Both cocaine and cocaethylene functioned as reinforcers under the PR and concurrent choice schedules of reinforcement. Under the PR schedule, peak BPs were not significantly different, nor were ED50 values on the ascending limb, suggesting that cocaethylene has equal reinforcing strength and potency to cocaine. Under the concurrent drug-food choice procedure, cocaethylene was also equally potent to cocaine.
CONCLUSIONS
Under two schedules of reinforcement designed to assess reinforcing strength, cocaethylene and cocaine were equipotent and of equal reinforcing strength. Because cocaethylene has a longer duration of action, it is important for studies designed to evaluate treatments for cocaine use to also consider the effects of these interventions on cocaethylene.
Identifiants
pubmed: 37699287
pii: S0376-8716(23)01190-0
doi: 10.1016/j.drugalcdep.2023.110952
pmc: PMC10538368
mid: NIHMS1931936
pii:
doi:
Substances chimiques
cocaethylene
FJO3071W5Y
Cocaine
I5Y540LHVR
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
110952Subventions
Organisme : NIDA NIH HHS
ID : F31 DA053776
Pays : United States
Organisme : NIDA NIH HHS
ID : P50 DA006634
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA017763
Pays : United States
Organisme : NIDA NIH HHS
ID : T32 DA041349
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None.
Références
Drug Alcohol Depend. 2013 Nov 1;133(1):94-9
pubmed: 23810644
J Pharmacol Exp Ther. 2000 May;293(2):383-9
pubmed: 10773006
J Pharmacol Exp Ther. 2020 Jul;374(1):1-5
pubmed: 32269168
Exp Clin Psychopharmacol. 2000 Feb;8(1):117-124
pubmed: 10743912
J Neurochem. 1993 Apr;60(4):1429-35
pubmed: 8455033
Brain Res. 2001 Oct 12;915(2):176-84
pubmed: 11595207
Psychopharmacology (Berl). 1994 Dec;116(4):428-32
pubmed: 7701044
J Pharmacol Exp Ther. 2023 Mar;384(3):372-381
pubmed: 36507847
Pharmacol Biochem Behav. 2002 Jul;72(4):931-6
pubmed: 12062583
J Pharmacol Exp Ther. 1997 Oct;283(1):164-76
pubmed: 9336321
Psychopharmacology (Berl). 1995 Aug;120(3):296-302
pubmed: 8524977
Addict Behav. 2021 Sep;120:106950
pubmed: 33940336
Life Sci. 1992;50(18):1351-61
pubmed: 1532847
Recent Dev Alcohol. 1992;10:37-56
pubmed: 1317047
Drug Alcohol Depend. 1990 Feb;25(1):97-104
pubmed: 2323315
Addiction. 2002 Jul;97(7):773-83
pubmed: 12133112
Drug Alcohol Depend. 2003 Nov 24;72(2):169-82
pubmed: 14636972
Neuropsychopharmacology. 2023 Apr 28;:
pubmed: 37118057
J Pharmacol Exp Ther. 1995 Jul;274(1):215-23
pubmed: 7616402
J Psychoactive Drugs. 1992 Jul-Sep;24(3):273-6
pubmed: 1432406
Psychopharmacology (Berl). 1993;111(1):39-46
pubmed: 7870932
Eur J Pharmacol. 1991 May 17;197(2-3):235-6
pubmed: 1915572
J Neurochem. 1991 Feb;56(2):698-701
pubmed: 1988563
Drug Alcohol Depend. 2018 Nov 1;192:16-28
pubmed: 30195242
Psychopharmacology (Berl). 2000 Apr;149(2):153-62
pubmed: 10805610
Prog Brain Res. 2016;224:3-24
pubmed: 26822351
Life Sci. 1991;48(18):1787-94
pubmed: 2020260