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  • 1.
    Fredriksson, Ida
    et al.
    Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD, USA.
    Applebey, Sarah V
    Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD.
    Minier-Toribio, Angelica
    Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD.
    Shekara, Aniruddha
    Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD.
    Bossert, Jennifer M.
    Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD.
    Shaham, Yavin
    Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD, USA.
    Effect of the dopamine stabilizer (-)-OSU6162 on potentiated incubation of opioid craving after electric barrier-induced voluntary abstinence.2020In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 45, no 5, p. 770-779Article in journal (Refereed)
    Abstract [en]

    In the classical incubation of drug craving rat model, drug seeking is assessed after homecage forced abstinence. However, human abstinence is often voluntary because negative consequences of drug seeking outweigh the desire for the drug. Here, we developed a rat model of incubation of opioid craving after electric barrier-induced voluntary abstinence and determined whether the dopamine stabilizer (-)-OSU6162 would decrease this new form of incubation. We trained male and female rats to self-administer oxycodone (0.1 mg/kg/infusion, 6 h/day) for 14 days. We then exposed them to either homecage forced abstinence or voluntary abstinence induced by an electric barrier of increasing intensity near the drug-paired lever. On abstinence days 1, 15, or 30, we tested the rats for oxycodone seeking without shock and drug. We also examined the effect of (-)-OSU6162 (7.5 and 15 mg/kg) on oxycodone seeking on abstinence day 1 or after 15 days of either voluntary or forced abstinence. Independent of sex, the time-dependent increase in oxycodone seeking after cessation of opioid self-administration (incubation of opioid craving) was stronger after voluntary abstinence than after forced abstinence. In males, (-)-OSU6162 decreased incubated (day 15) but not non-incubated (day 1) oxycodone seeking after either voluntary or forced abstinence. In females, (-)-OSU6162 modestly decreased incubated oxycodone seeking after voluntary but not forced abstinence. Results suggest that voluntary abstinence induced by negative consequences of drug seeking can paradoxically potentiate opioid craving and relapse. We propose the dopamine stabilizer (-)-OSU6162 may serve as an adjunct pharmacological treatment to prevent relapse in male opioid users.

  • 2.
    Fredriksson, Ida
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. NIDA, MD 21224 USA.
    Venniro, Marco
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. NIDA, MD 21224 USA.
    Reiner, David J.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. NIDA, MD 21224 USA.
    Chow, Jonathan J.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. NIDA, MD 21224 USA.
    Bossert, Jennifer M.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. NIDA, MD 21224 USA.
    Shaham, Yavin
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. NIDA, MD 21224 USA.
    Animal Models of Drug Relapse and Craving after Voluntary Abstinence: A Review2021In: Pharmacological Reviews, ISSN 0031-6997, E-ISSN 1521-0081, Vol. 73, no 3, p. 1050-1083Article, review/survey (Refereed)
    Abstract [en]

    Relapse to drug use during abstinence is a defining feature of addiction. During the last several decades, this clinical scenario has been studied at the preclinical level using classic relapse/reinstatement models in which drug seeking is assessed after experimenter-imposed home-cage forced abstinence or extinction of the drug-reinforced responding in the self-administration chambers. To date, however, results from studies using rat relapse/reinstatement models have yet to result in Food and Drug Administration-approved medications for relapse prevention. The reasons for this state of affairs are complex and multifaceted, but one potential reason is that, in humans, abstinence is often self-imposed or voluntary and occurs either because the negative consequences of drug use outweigh the drugs rewarding effects or because of the availability of nondrug alternative rewards that are chosen over the drug. Based on these considerations, we and others have recently developed rat models of relapse after voluntary abstinence, achieved either by introducing adverse consequences to drug taking (punishment) or seeking (electric barrier) or by providing mutually exclusive choices between the self-administered drug and nondrug rewards (palatable food or social interaction). In this review, we provide an overview of these translationally relevant relapse models and discuss recent neuropharmacological findings from studies using these models. We also discuss sex as a biological variable, future directions, and clinical implications of results from relapse studies using voluntary abstinence models. Our main conclusion is that the neuropharmacological mechanisms controlling relapse to drug seeking after voluntary abstinence are often different from the mechanisms controlling relapse after home-cage forced abstinence or reinstatement after extinction. Significance Statement-This review describes recently developed rat models of relapse after voluntary abstinence, achieved either by introducing adverse consequences to drug taking or seeking or by providing mutually exclusive choices between the self-administered drug and nondrug rewards. This review discusses recent neuropharmacological findings from studies using these models and discusses future directions and clinical implications.

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