Dose-extending placebo effect in a rat model of buprenorphine maintenance treatment.
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| Title: | Dose-extending placebo effect in a rat model of buprenorphine maintenance treatment. |
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| Authors: | Pitts, Kayla M. (AUTHOR), Pilz, Emma M. (AUTHOR), Colloca, Luana (AUTHOR), Shaham, Yavin (AUTHOR), Chow, Jonathan J. (AUTHOR) |
| Source: | Psychopharmacology. May2026, Vol. 243 Issue 5, p1225-1236. 12p. |
| Subjects: | Buprenorphine, Opioids, Placebos, Animal disease models, Drug administration, Treatment of addictions, Remifentanil |
| 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. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| 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. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00333158 |
| DOI: | 10.1007/s00213-025-06815-w |
