Kayla M Pitts, Emma M Pilz, Luana Colloca, Yavin Shaham, Jonathan J Chow
{"title":"Dose-extending placebo effect in a rat model of buprenorphine maintenance treatment.","authors":"Kayla M Pitts, Emma M Pilz, Luana Colloca, Yavin Shaham, Jonathan J Chow","doi":"10.1007/s00213-025-06815-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale and objective: </strong>Clinical studies have shown that exposure to placebos or combining placebos with a lower medication dose can mimic the effect of a higher effective medication dose. This \"dose-extending placebo effect\" has been demonstrated in treatment for pain and other medical conditions but not in addiction. Here, we tested if a \"dose-extending placebo effect\" occurs in a rat model of opioid (buprenorphine) maintenance.</p><p><strong>Methods: </strong>We trained 27 rats to self-administer remifentanil (5 µg/kg/infusion, 1-h per day). Next, we implanted some rats with buprenorphine minipumps (3 mg/kg/day, Exp. 1) or pretreated others with daily intravenous buprenorphine (0.3 mg/kg, Exp. 2), and introduced a discriminative cue (houselight + tone) during the self-administration sessions (the buprenorphine-maintenance cue). After discontinuing buprenorphine treatment, we retrained the rats for remifentanil self-administration without the cue. Next, we tested the effect of low and high buprenorphine doses (0.15 and 0.3 mg/kg), the buprenorphine-maintenance cue, and the combination of the low-dose with the cue on remifentanil self-administration.</p><p><strong>Results: </strong>Rats learned to self-administer remifentanil, and buprenorphine maintenance suppressed drug self-administration. The low buprenorphine dose modestly decreased self-administration, while the high dose caused a strong inhibition. Tests for the \"dose-extending placebo effect\" showed that discriminative buprenorphine cue alone had no effect, while the low dose plus the buprenorphine cue mimicked the inhibitory effect of the high dose.</p><p><strong>Conclusions: </strong>This proof-of-concept study suggests that a \"dose-extending placebo effect\" can be modeled in rats undergoing opioid maintenance. This approach could support dose-reduction strategies in humans undergoing opioid maintenance therapy.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06815-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Rationale and objective: Clinical studies have shown that exposure to placebos or combining placebos with a lower medication dose can mimic the effect of a higher effective medication dose. This "dose-extending placebo effect" has been demonstrated in treatment for pain and other medical conditions but not in addiction. Here, we tested if a "dose-extending placebo effect" occurs in a rat model of opioid (buprenorphine) maintenance.
Methods: We trained 27 rats to self-administer remifentanil (5 µg/kg/infusion, 1-h per day). Next, we implanted some rats with buprenorphine minipumps (3 mg/kg/day, Exp. 1) or pretreated others with daily intravenous buprenorphine (0.3 mg/kg, Exp. 2), and introduced a discriminative cue (houselight + tone) during the self-administration sessions (the buprenorphine-maintenance cue). After discontinuing buprenorphine treatment, we retrained the rats for remifentanil self-administration without the cue. Next, we tested the effect of low and high buprenorphine doses (0.15 and 0.3 mg/kg), the buprenorphine-maintenance cue, and the combination of the low-dose with the cue on remifentanil self-administration.
Results: Rats learned to self-administer remifentanil, and buprenorphine maintenance suppressed drug self-administration. The low buprenorphine dose modestly decreased self-administration, while the high dose caused a strong inhibition. Tests for the "dose-extending placebo effect" showed that discriminative buprenorphine cue alone had no effect, while the low dose plus the buprenorphine cue mimicked the inhibitory effect of the high dose.
Conclusions: This proof-of-concept study suggests that a "dose-extending placebo effect" can be modeled in rats undergoing opioid maintenance. This approach could support dose-reduction strategies in humans undergoing opioid maintenance therapy.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
