Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individuals

Greenwald, Mark K.; Lundahl, Leslie H.; Steinmiller, Caren L.

doi:10.1007/s00213-012-2868-9

Cited by 48 publications

(43 citation statements)

References 66 publications

(83 reference statements)

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“…First is the translational utility of this stressor: YOH reliably reinstates drug seeking or conditioned drug effects in mice (Mantsch et al, 2010), rats (Richards et al, 2008; Shepard et al, 2004), and monkeys (Lee et al, 2004). It also provokes drug craving in detoxified alcoholics (Umhau et al, 2011) and methadone-maintained patients (Stine et al, 2002), and increases opiate-taking behavior in buprenorphine-maintained individuals (Greenwald et al, 2013). The effectiveness of YOH in humans and animals recommends it for use in animal experiments designed to help understand the clinical problem of relapse to stress-induced drug seeking.…”

Section: Discussionmentioning

confidence: 99%

Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats

Grella

Funk

Coen

et al. 2014

Behavioural Brain Research

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Rationale The correlation between stress and smoking is well established. The mechanisms that underlie this relationship are, however, unclear. Recent data suggest the kappa-opioid system is involved in the mediation of negative affective states associated with stress thereby promoting drug addiction and relapse. Pharmacological treatments targeting the kappa opioid system and this mechanism may prove to be useful therapeutics for nicotine addiction in the future. Objectives We sought to determine whether there was a stress-specific role of the kappa opioid system in nicotine seeking behavior. Method Groups of male Long Evans rats were trained to self-administer nicotine intravenously; their operant responding for nicotine was extinguished prior to tests of reinstatement. Pretreatment with systemic injections of the kappa opioid receptor (KOR) antagonist nor-binaltorphimine (nor-BNI) was given prior to tests of stress (systemic injections of yohimbine (YOH)) or cue-induced reinstatement of nicotine seeking. Systemic injections of the KOR agonist U50,488 were also given in a test for reinstatement of nicotine seeking. Results Nor-BNI pretreatment at 1 hr and 24 hrs prior to testing was able to block YOH-induced, but not cue-induced reinstatement of nicotine seeking. U50,488 reinstated nicotine seeking behavior in a dose-dependent manner. Conclusions These findings support the hypothesis that the kappa opioid system is involved in relapse to nicotine seeking induced by stress, but not by conditioned cues. KOR antagonists such as nor-BNI may therefore be useful novel therapeutic agents for decreasing the risk of stress-induced drug relapse.

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Section: Discussionmentioning

confidence: 99%

Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats

Grella

Funk

Coen

et al. 2014

Behavioural Brain Research

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“…Opioid reinforcement is measured using operant drug self-administration procedures whereby participants work on a computer task to earn drug (e.g., Comer et al, 2001; Greenwald et al, 2013; Mello et al, 1982). Subjective drug-effect assessments include adjective ratings that reflect abuse potential (e.g., “liking”, “good effect”).…”

Section: Introductionmentioning

confidence: 99%

Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: Implications for clinical use and policy

Greenwald

Comer

Fiellin

2014

Drug and Alcohol Dependence

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137

118

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Background Sublingual formulations of buprenorphine (BUP) and BUP/naloxone have well-established pharmacokinetic and pharmacodynamic profiles, and are safe and effective for treating opioid use disorder. Since approvals of these formulations, their clinical use has increased. Yet, questions have arisen as to how BUP binding to mu-opioid receptors (μORs), the neurobiological target for this medication, relate to its clinical application. BUP produces dose- and time-related alterations of μOR availability but some clinicians express concern about whether doses higher than those needed to prevent opioid withdrawal symptoms are warranted, and policymakers consider limiting reimbursement for certain BUP dosing regimens. Methods We review scientific data concerning BUP-induced changes in μOR availability and their relationship to clinical efficacy. Results Withdrawal suppression appears to require ≤50% μOR availability, associated with BUP trough plasma concentrations ≥1 ng/mL; for most patients, this may require single daily BUP doses of 4-mg to defend against trough levels, or lower divided doses. Blockade of the reinforcing and subjective effects of typical doses of abused opioids require <20% μOR availability, associated with BUP trough plasma concentrations ≥3 ng/mL; for most individuals, this may require single daily BUP doses >16-mg, or lower divided doses. For individuals attempting to surmount this blockade with higher-than-usual doses of abused opioids, even larger BUP doses and <10% μOR availability would be required. Conclusion For these reasons, and given the complexities of studies on this issue and comorbid problems, we conclude that fixed, arbitrary limits on BUP doses in clinical care or limits on reimbursement for this care are unwarranted.

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“…Acute stress, then, may elevate drug seeking and taking as a consequence of increasing cognitive impulsivity. Stress effects on drug seeking and using are well established: acute stress potently contributes to relapse to drug taking in addicts (Breese et al 2011; Goeders 2002; Higley et al 2011; Sinha et al 2011), and the pharmacological stressor yohimbine increases opioid-seeking in heroin-dependent individuals (Greenwald et al 2013) and reinstates drug seeking in animal models (e.g. (Banna et al 2010; Ghitza et al 2006; Le et al 2005; Shepard et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine

2014

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Rationale Stress-induced disruption of decision making has been hypothesized to contribute to drug-seeking behaviors and addiction. Noradrenergic signaling plays a central role in mediating stress responses. However, the effects of acute stress on decision making, and the role of noradrenergic signaling in regulating these effects, have not been well characterized. Objective To characterize changes in decision making caused by acute pharmacological stress, the effects of yohimbine (an α2-adrenergic antagonist) were examined in a delay discounting task. Noradrenergic contributions to decision making were further characterized by examining the effects of propranolol (a β antagonist), prazosin (an αl antagonist), and guanfacine (an α2 agonist). Methods Sprague-Dawley rats were administered drugs prior to performance on a delay discounting task, in which the delay preceding the large reward increased within each session (ascending delays). To dissociate drug-induced changes in delay sensitivity from behavioral inflexibility, drug effects were subsequently tested in a modified version of the discounting task, in which the delay preceding the large reward decreased within each session (descending delays). Results Yohimbine increased choice of the large reward when tested with ascending delays but decreased choice of the same large reward when tested with descending delays, suggesting that drug effects could be attributed to perseverative choice of the lever preferred at the beginning of the session. Propranolol increased choice of the large reward when tested with ascending delays. Prazosin and guanfacine had no effect on reward choice. Conclusions The stress-like effects of yohimbine administration may impair decision making by causing inflexible, perseverative behavior.

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Yohimbine increases opioid-seeking behavior in heroin-dependent, buprenorphine-maintained individuals

Cited by 48 publications

References 66 publications

Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats

Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats

Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: Implications for clinical use and policy

Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine

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