Amitifadine, a triple reuptake inhibitor, reduces self-administration of the opiate remifentanil in rats.

dc.contributor.author

Levin, Edward D

dc.contributor.author

Wells, Corinne

dc.contributor.author

Hawkey, Andrew

dc.contributor.author

Holloway, Zade

dc.contributor.author

Blair, Graham

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Vierling, Alexander

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Ko, Ashley

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Pace, Caroline

dc.contributor.author

Modarres, John

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McKinney, Anthony

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Rezvani, Amir H

dc.contributor.author

Rose, Jed E

dc.date.accessioned

2023-12-06T16:30:10Z

dc.date.available

2023-12-06T16:30:10Z

dc.date.issued

2020-06

dc.date.updated

2023-12-06T16:30:09Z

dc.description.abstract

Rationale

A variety of neural systems are involved in drug addiction, and some of these systems are shared across different addictive drugs. We have found several different types of drug treatments that successfully reduce nicotine self-administration.

Objectives

The current set of studies is the first in a series to determine if drug treatments that have been found to significantly reduce nicotine self-administration would reduce opiate self-administration.

Methods

Amitifadine, a triple reuptake inhibitor of dopamine, norepinephrine, and serotonin, was assessed in female Sprague-Dawley rats to determine whether it significantly reduces remifentanil self-administration with either acute or chronic treatment.

Results

Acutely, amitifadine doses of 5, 10, and 20 mg/kg each significantly reduced remifentanil self-administration. In a chronic study, repeated treatment with 10 mg/kg of amitifadine continued to reduce remifentanil self-administration, even after the cessation of treatment. However, amitifadine was not found to attenuate the rise in remifentanil self-administration with continued access. This study and our earlier one showed that the 10 mg/kg amitifadine dose did not significantly affect food motivated responding. Amitifadine did not attenuate remifentanil-induced antinociception as measured on the hot plate test but extended and maintained antinociceptive effects.

Conclusions

These studies show the promise of amitifadine as a treatment for countering opiate self-administration for adjunctive use with opioids for analgesia. Further studies are needed to determine the possible efficacy of amitifadine for combating opiate addiction or preventing it in humans during adjunctive use with opioids for chronic pain.
dc.identifier

10.1007/s00213-020-05489-w

dc.identifier.issn

0033-3158

dc.identifier.issn

1432-2072

dc.identifier.uri

https://hdl.handle.net/10161/29502

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Psychopharmacology

dc.relation.isversionof

10.1007/s00213-020-05489-w

dc.subject

Animals

dc.subject

Humans

dc.subject

Rats

dc.subject

Rats, Sprague-Dawley

dc.subject

Pain

dc.subject

Norepinephrine

dc.subject

Dopamine

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Serotonin

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Aza Compounds

dc.subject

Nicotine

dc.subject

Dopamine Uptake Inhibitors

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Analgesics, Opioid

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Self Administration

dc.subject

Motivation

dc.subject

Dose-Response Relationship, Drug

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Stereoisomerism

dc.subject

Female

dc.subject

Bridged Bicyclo Compounds, Heterocyclic

dc.subject

Remifentanil

dc.subject

Selective Serotonin Reuptake Inhibitors

dc.title

Amitifadine, a triple reuptake inhibitor, reduces self-administration of the opiate remifentanil in rats.

dc.type

Journal article

duke.contributor.orcid

Levin, Edward D|0000-0001-7292-8084|0000-0002-5060-9602

pubs.begin-page

1681

pubs.end-page

1689

pubs.issue

6

pubs.organisational-group

Duke

pubs.organisational-group

Nicholas School of the Environment

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School of Medicine

pubs.organisational-group

Trinity College of Arts & Sciences

pubs.organisational-group

Basic Science Departments

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Clinical Science Departments

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Pharmacology & Cancer Biology

pubs.organisational-group

Psychiatry & Behavioral Sciences

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Duke Cancer Institute

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Psychology & Neuroscience

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Environmental Sciences and Policy

pubs.organisational-group

Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Institute for Brain Sciences

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Initiatives

pubs.organisational-group

Duke Science & Society

pubs.organisational-group

Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

pubs.publication-status

Published

pubs.volume

237

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