+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Dopamine D 3 Receptor Antagonism Reverses the Escalation of Oxycodone Self-administration and Decreases Withdrawal-Induced Hyperalgesia and Irritability-Like Behavior in Oxycodone-Dependent Heterogeneous Stock Rats


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Prescription opioids, such as oxycodone, are highly effective analgesics for clinical pain management, but approximately 25% of patients who are prescribed opioids misuse them, and 5%–10% develop an opioid use disorder (OUD). Effective therapies for the prevention and treatment of opioid abuse and addiction need to be developed. The present study evaluated the effects of the highly selective dopamine D 3 receptor antagonist VK4-116 ([R]- N-[4-(4-[3-chloro-5-ethyl-2-methoxyphenyl]piperazin-1-yl)-3-hydroxybutyl]-1 H-indole-2-carboxamide) on oxycodone addictive-like behaviors. We used a model of extended access to oxycodone self-administration and tested the effects of VK4-116 on the escalation of oxycodone self-administration and withdrawal-induced hyperalgesia and irritability-like behavior in male and female rats. Pretreatment with VK4-116 (5–25 mg/kg, i.p.) dose-dependently decreased the escalation of oxycodone self-administration and reduced withdrawal-induced hyperalgesia and irritability-like behavior in opioid-dependent rats. These findings demonstrate a key role for D 3 receptors in both the motivation to take opioids and negative emotional states that are associated with opioid withdrawal and suggest that D 3 receptor antagonism may be a viable therapeutic approach for the treatment of OUD.

          Related collections

          Most cited references61

          • Record: found
          • Abstract: found
          • Article: found

          The Prescription Opioid and Heroin Crisis: A Public Health Approach to an Epidemic of Addiction

          Annual Review of Public Health, 36(1), 559-574
            • Record: found
            • Abstract: not found
            • Article: not found

            Relationship between Nonmedical Prescription-Opioid Use and Heroin Use

              • Record: found
              • Abstract: found
              • Article: not found

              Transition from moderate to excessive drug intake: change in hedonic set point.

              Differential access to cocaine self-administration produced two patterns of drug intake in rats. With 1 hour of access per session, drug intake remained low and stable. In contrast, with 6 hours of access, drug intake gradually escalated over days. After escalation, drug consumption was characterized by an increased early drug loading and an upward shift in the cocaine dose-response function, suggesting an increase in hedonic set point. After 1 month of abstinence, escalation of cocaine intake was reinstated to a higher level than before. These findings may provide an animal model for studying the development of excessive drug intake and the basis of addiction.

                Author and article information

                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                14 January 2020
                : 13
                : 292
                [1] 1Department of Psychiatry, University of California, San Diego, La Jolla , CA, United States
                [2] 2Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program , Baltimore, MD, United States
                Author notes

                Edited by: Antonio Ferragud, University of Cambridge, United Kingdom

                Reviewed by: Andrea Cippitelli, Florida Atlantic University, United States; Marco Pravetoni, University of Minnesota Twin Cities, United States

                *Correspondence: Giordano de Guglielmo gdeguglielmo@ 123456health.ucsd.edu Olivier George olgeorge@ 123456health.ucsd.edu

                Specialty section: This article was submitted to Emotion Regulation and Processing, a section of the journal Frontiers in Behavioral Neuroscience

                Copyright © 2020 de Guglielmo, Kallupi, Sedighim, Newman and George.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 02 October 2019
                : 23 December 2019
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 71, Pages: 10, Words: 7193
                Funded by: National Institute on Drug Abuse 10.13039/100000026
                Award ID: DA04445
                Behavioral Neuroscience
                Original Research

                vk4-116, escalation, opioid, dependance, withdrawal


                Comment on this article