A drug-vs-food “choice” self-administration procedure in rats to investigate pharmacological and environmental mechanisms of substance use disorders

•Surgical technique resulted in median first catheter life of 18 weeks.•Intravenous drug-vs-food choice could be trained in rats within ∼27 sessions.•Opioid, stimulant, and opioid + stimulant drug-vs-food choice was established.•Consistency between monkey and rat drug choice results supports transla...

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Published inJournal of neuroscience methods Vol. 354; p. 109110
Main Authors Townsend, E. Andrew, Schwienteck, Kathryn L., Robinson, Hannah L., Lawson, Stephen T., Banks, Matthew L.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 15.04.2021
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ISSN0165-0270
1872-678X
1872-678X
DOI10.1016/j.jneumeth.2021.109110

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Abstract •Surgical technique resulted in median first catheter life of 18 weeks.•Intravenous drug-vs-food choice could be trained in rats within ∼27 sessions.•Opioid, stimulant, and opioid + stimulant drug-vs-food choice was established.•Consistency between monkey and rat drug choice results supports translatability. Preclinical drug self-administration procedures are commonly used to investigate expression, mechanisms, and treatment of substance use disorders. The aims were to back-translate an intravenous drug-vs-food choice procedure primarily utilized in monkeys to male and female rats and to develop a surgical method for sustained intravenous catheter patency suitable for long-term drug-choice studies. The surgical protocol resulted in a median intravenous jugular catheter patency in male and female rats of 126 days (range: 25–365 days). Drug-vs-food choice was established with opioids (fentanyl and heroin), psychostimulants (cocaine, methamphetamine, and amphetamine), and an opioid/psychostimulant mixture (fentanyl + methamphetamine). The average time from catheter implantation to stable choice behavior across all drugs was 27 sessions (range: 16–44 sessions). Choice behavior stabilized more quickly for cocaine and fentanyl than for other drugs. Manipulations of both environmental variables (e.g., response requirement or food reinforcer magnitude) and pharmacological variables (e.g., extended access drug self-administration or continuous buprenorphine treatment via osmotic pump) significantly shifted opioid-vs-food choice consistent with previous monkey studies. Duration of intravenous catheter patency in rats was suitable for long-term, within-subject drug choice studies. Effects of environmental and pharmacological manipulations in rats confirmed and extended previous results from monkeys. The concordance of behavioral results between rats and monkeys using the present drug-vs-food choice procedure supports its utility to improve our basic understanding of the expression and mechanisms of substance use disorders towards to development of more effective therapeutics.
AbstractList Preclinical drug self-administration procedures are commonly used to investigate expression, mechanisms, and treatment of substance use disorders. The aims were to back-translate an intravenous drug-vs-food choice procedure primarily utilized in monkeys to male and female rats and to develop a surgical method for sustained intravenous catheter patency suitable for long-term drug-choice studies. The surgical protocol resulted in a median intravenous jugular catheter patency in male and female rats of 126 days (range: 25-365 days). Drug-vs-food choice was established with opioids (fentanyl and heroin), psychostimulants (cocaine, methamphetamine, and amphetamine), and an opioid/psychostimulant mixture (fentanyl + methamphetamine). The average time from catheter implantation to stable choice behavior across all drugs was 27 sessions (range: 16-44 sessions). Choice behavior stabilized more quickly for cocaine and fentanyl than for other drugs. Manipulations of both environmental variables (e.g., response requirement or food reinforcer magnitude) and pharmacological variables (e.g., extended access drug self-administration or continuous buprenorphine treatment via osmotic pump) significantly shifted opioid-vs-food choice consistent with previous monkey studies. Duration of intravenous catheter patency in rats was suitable for long-term, within-subject drug choice studies. Effects of environmental and pharmacological manipulations in rats confirmed and extended previous results from monkeys. The concordance of behavioral results between rats and monkeys using the present drug-vs-food choice procedure supports its utility to improve our basic understanding of the expression and mechanisms of substance use disorders towards to development of more effective therapeutics.
Preclinical drug self-administration procedures are commonly used to investigate expression, mechanisms, and treatment of substance use disorders.BACKGROUNDPreclinical drug self-administration procedures are commonly used to investigate expression, mechanisms, and treatment of substance use disorders.The aims were to back-translate an intravenous drug-vs-food choice procedure primarily utilized in monkeys to male and female rats and to develop a surgical method for sustained intravenous catheter patency suitable for long-term drug-choice studies.NEW METHODThe aims were to back-translate an intravenous drug-vs-food choice procedure primarily utilized in monkeys to male and female rats and to develop a surgical method for sustained intravenous catheter patency suitable for long-term drug-choice studies.The surgical protocol resulted in a median intravenous jugular catheter patency in male and female rats of 126 days (range: 25-365 days). Drug-vs-food choice was established with opioids (fentanyl and heroin), psychostimulants (cocaine, methamphetamine, and amphetamine), and an opioid/psychostimulant mixture (fentanyl + methamphetamine). The average time from catheter implantation to stable choice behavior across all drugs was 27 sessions (range: 16-44 sessions). Choice behavior stabilized more quickly for cocaine and fentanyl than for other drugs. Manipulations of both environmental variables (e.g., response requirement or food reinforcer magnitude) and pharmacological variables (e.g., extended access drug self-administration or continuous buprenorphine treatment via osmotic pump) significantly shifted opioid-vs-food choice consistent with previous monkey studies.RESULTSThe surgical protocol resulted in a median intravenous jugular catheter patency in male and female rats of 126 days (range: 25-365 days). Drug-vs-food choice was established with opioids (fentanyl and heroin), psychostimulants (cocaine, methamphetamine, and amphetamine), and an opioid/psychostimulant mixture (fentanyl + methamphetamine). The average time from catheter implantation to stable choice behavior across all drugs was 27 sessions (range: 16-44 sessions). Choice behavior stabilized more quickly for cocaine and fentanyl than for other drugs. Manipulations of both environmental variables (e.g., response requirement or food reinforcer magnitude) and pharmacological variables (e.g., extended access drug self-administration or continuous buprenorphine treatment via osmotic pump) significantly shifted opioid-vs-food choice consistent with previous monkey studies.Duration of intravenous catheter patency in rats was suitable for long-term, within-subject drug choice studies. Effects of environmental and pharmacological manipulations in rats confirmed and extended previous results from monkeys.COMPARISON WITH EXISTING METHODSDuration of intravenous catheter patency in rats was suitable for long-term, within-subject drug choice studies. Effects of environmental and pharmacological manipulations in rats confirmed and extended previous results from monkeys.The concordance of behavioral results between rats and monkeys using the present drug-vs-food choice procedure supports its utility to improve our basic understanding of the expression and mechanisms of substance use disorders towards to development of more effective therapeutics.CONCLUSIONSThe concordance of behavioral results between rats and monkeys using the present drug-vs-food choice procedure supports its utility to improve our basic understanding of the expression and mechanisms of substance use disorders towards to development of more effective therapeutics.
•Surgical technique resulted in median first catheter life of 18 weeks.•Intravenous drug-vs-food choice could be trained in rats within ∼27 sessions.•Opioid, stimulant, and opioid + stimulant drug-vs-food choice was established.•Consistency between monkey and rat drug choice results supports translatability. Preclinical drug self-administration procedures are commonly used to investigate expression, mechanisms, and treatment of substance use disorders. The aims were to back-translate an intravenous drug-vs-food choice procedure primarily utilized in monkeys to male and female rats and to develop a surgical method for sustained intravenous catheter patency suitable for long-term drug-choice studies. The surgical protocol resulted in a median intravenous jugular catheter patency in male and female rats of 126 days (range: 25–365 days). Drug-vs-food choice was established with opioids (fentanyl and heroin), psychostimulants (cocaine, methamphetamine, and amphetamine), and an opioid/psychostimulant mixture (fentanyl + methamphetamine). The average time from catheter implantation to stable choice behavior across all drugs was 27 sessions (range: 16–44 sessions). Choice behavior stabilized more quickly for cocaine and fentanyl than for other drugs. Manipulations of both environmental variables (e.g., response requirement or food reinforcer magnitude) and pharmacological variables (e.g., extended access drug self-administration or continuous buprenorphine treatment via osmotic pump) significantly shifted opioid-vs-food choice consistent with previous monkey studies. Duration of intravenous catheter patency in rats was suitable for long-term, within-subject drug choice studies. Effects of environmental and pharmacological manipulations in rats confirmed and extended previous results from monkeys. The concordance of behavioral results between rats and monkeys using the present drug-vs-food choice procedure supports its utility to improve our basic understanding of the expression and mechanisms of substance use disorders towards to development of more effective therapeutics.
ArticleNumber 109110
Author Robinson, Hannah L.
Schwienteck, Kathryn L.
Banks, Matthew L.
Lawson, Stephen T.
Townsend, E. Andrew
AuthorAffiliation 1 Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA 23298
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Keywords Fentanyl
Drug self-administration
Cocaine
Choice
Heroin
Methamphetamine
Language English
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Drew Townsend: Methodology, Software, Formal analysis, Investigation, Data curation, Writing – Review and Editing, Visualization. Kathryn Schwienteck: Methodology, Formal analysis, Investigation, Data curation, Writing – Original Draft, Visualization. Hannah Robinson: Methodology, Investigation, Data curation, Writing – Review and Editing, Visualization. Stephen Lawson: Investigation, Data curation, Writing – Review and Editing. Matthew Banks: Formal analysis, Writing – Original Draft, Writing – Review and Editing, Visualization, Conceptualization, Supervision, Funding acquisition.
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Snippet •Surgical technique resulted in median first catheter life of 18 weeks.•Intravenous drug-vs-food choice could be trained in rats within ∼27 sessions.•Opioid,...
Preclinical drug self-administration procedures are commonly used to investigate expression, mechanisms, and treatment of substance use disorders. The aims...
Preclinical drug self-administration procedures are commonly used to investigate expression, mechanisms, and treatment of substance use...
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StartPage 109110
SubjectTerms Animals
Choice
Choice Behavior
Cocaine
Dose-Response Relationship, Drug
Drug self-administration
Female
Fentanyl
Food Preferences
Heroin
Male
Methamphetamine
Pharmaceutical Preparations
Rats
Self Administration
Substance-Related Disorders - etiology
Title A drug-vs-food “choice” self-administration procedure in rats to investigate pharmacological and environmental mechanisms of substance use disorders
URI https://dx.doi.org/10.1016/j.jneumeth.2021.109110
https://www.ncbi.nlm.nih.gov/pubmed/33705855
https://www.proquest.com/docview/2501267969
https://pubmed.ncbi.nlm.nih.gov/PMC8082467
Volume 354
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