Samidorphan, an opioid receptor antagonist, attenuates drug-induced increases in extracellular dopamine concentrations and drug self-administration in male Wistar rats
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved..
Opioid receptors modulate neurochemical and behavioral responses to drugs of abuse in nonclinical models. Samidorphan (SAM) is a new molecular entity that binds with high affinity to human mu- (μ), kappa- (κ), and delta- (δ) opioid receptors and functions as a μ-opioid receptor antagonist with partial agonist activity at κ- and δ-opioid receptors. Based on its in vitro profile, we hypothesized that SAM would block key neurobiological effects of drugs of abuse. Therefore, we assessed the effects of SAM on ethanol-, oxycodone-, cocaine-, and amphetamine-induced increases in extracellular dopamine (DAext) in the nucleus accumbens shell (NAc-sh), and ethanol and cocaine self-administration behavior in rats. In microdialysis studies, administration of SAM alone did not result in measurable changes in NAc-sh DAext when given across a large range of doses. However, SAM markedly decreased average and maximal increases in NAc-sh DAext produced by each of the drugs of abuse tested. In behavioral studies, SAM attenuated fixed-ratio ethanol self-administration and progressive ratio cocaine self-administration. These results highlight the potential of SAM to counteract the neurobiological and behavioral effects of several drugs of abuse with differing mechanisms of action.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:204 |
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| Enthalten in: |
Pharmacology, biochemistry, and behavior - 204(2021) vom: 01. Mai, Seite 173157 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cunningham, Jacobi I [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.10.2021 Date Revised 08.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.pbb.2021.173157 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322049229 |
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| 100 | 1 | |a Cunningham, Jacobi I |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Samidorphan, an opioid receptor antagonist, attenuates drug-induced increases in extracellular dopamine concentrations and drug self-administration in male Wistar rats |
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| 500 | |a Date Completed 08.10.2021 | ||
| 500 | |a Date Revised 08.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Opioid receptors modulate neurochemical and behavioral responses to drugs of abuse in nonclinical models. Samidorphan (SAM) is a new molecular entity that binds with high affinity to human mu- (μ), kappa- (κ), and delta- (δ) opioid receptors and functions as a μ-opioid receptor antagonist with partial agonist activity at κ- and δ-opioid receptors. Based on its in vitro profile, we hypothesized that SAM would block key neurobiological effects of drugs of abuse. Therefore, we assessed the effects of SAM on ethanol-, oxycodone-, cocaine-, and amphetamine-induced increases in extracellular dopamine (DAext) in the nucleus accumbens shell (NAc-sh), and ethanol and cocaine self-administration behavior in rats. In microdialysis studies, administration of SAM alone did not result in measurable changes in NAc-sh DAext when given across a large range of doses. However, SAM markedly decreased average and maximal increases in NAc-sh DAext produced by each of the drugs of abuse tested. In behavioral studies, SAM attenuated fixed-ratio ethanol self-administration and progressive ratio cocaine self-administration. These results highlight the potential of SAM to counteract the neurobiological and behavioral effects of several drugs of abuse with differing mechanisms of action | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Dopamine | |
| 650 | 4 | |a Drug self-administration | |
| 650 | 4 | |a Drugs of abuse | |
| 650 | 4 | |a In vivo microdialysis | |
| 650 | 4 | |a Opioid | |
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| 700 | 1 | |a Azar, Marc R |e verfasserin |4 aut | |
| 700 | 1 | |a Koob, George F |e verfasserin |4 aut | |
| 700 | 1 | |a Deaver, Daniel R |e verfasserin |4 aut | |
| 700 | 1 | |a Eyerman, David J |e verfasserin |4 aut | |
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