Drug and alcohol dependence · 2026
The impact of α3β4 partial agonist AT-1001 on oxycodone withdrawal.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Contreras Katherine M, Palamar Alayna, Buzzi Belle, Oros Aleny, Buttar Burhan, Damaj Mariam, Zaveri Nurulain T, Walentiny D Matthew, Damaj M Imad
Аннотация
PURPOSE: Opioid withdrawal remains a major barrier to successful treatment of opioid use disorder. Non-opioid treatments such as clonidine and lofexidine reduce acute somatic symptoms but do not address affective and protracted withdrawal signs. Neuronal nicotinic acetylcholine receptors (nAChRs), particularly the α3β4⁎ subtype, are a promising alternative target implicated in opioid withdrawal. Here we investigated whether AT-1001, a high-affinity α3β4⁎ partial agonist, reduces somatic and affective signs of oxycodone withdrawal in mice.
EXPERIMENTAL APPROACH: Male and female C57BL/6J mice were rendered dependent on oxycodone (60mg/kg/day) or vehicle (0.9% saline) via a 7-day osmotic minipump infusion. Twenty-four hours after minipump removal, mice received an acute subcutaneous injection of vehicle, lofexidine (0.5mg/kg), or AT-1001 (0.3, 0.9, or 3mg/kg), followed by assessment of somatic withdrawal signs. In a separate cohort of oxycodone-dependent mice, animals received the highest dose of AT-1001 or lofexidine and were assessed two weeks post-minipump removal for mechanical sensitivity and anxiety-like behaviors (light/dark box assay).
KEY RESULTS: Our results showed that AT-1001 dose-dependently reduced somatic withdrawal signs in oxycodone-treated mice. In contrast to lofexidine, AT-1001 attenuated mechanical hypersensitivity and anxiety-like behavior compared to the vehicle group in oxycodone-dependent mice. Furthermore, AT-1001 had no significant effect on oxycodone-induced antinociception, as evaluated in the warm-water immersion assay.
CONCLUSION AND IMPLICATIONS: . Our findings suggest that AT-1001 effectively reduces oxycodone withdrawal signs without altering its antinociceptive effects. This supports α3β4⁎ partial agonists as promising candidates for further development as a safer and more comprehensive opioid withdrawal treatment.
EXPERIMENTAL APPROACH: Male and female C57BL/6J mice were rendered dependent on oxycodone (60mg/kg/day) or vehicle (0.9% saline) via a 7-day osmotic minipump infusion. Twenty-four hours after minipump removal, mice received an acute subcutaneous injection of vehicle, lofexidine (0.5mg/kg), or AT-1001 (0.3, 0.9, or 3mg/kg), followed by assessment of somatic withdrawal signs. In a separate cohort of oxycodone-dependent mice, animals received the highest dose of AT-1001 or lofexidine and were assessed two weeks post-minipump removal for mechanical sensitivity and anxiety-like behaviors (light/dark box assay).
KEY RESULTS: Our results showed that AT-1001 dose-dependently reduced somatic withdrawal signs in oxycodone-treated mice. In contrast to lofexidine, AT-1001 attenuated mechanical hypersensitivity and anxiety-like behavior compared to the vehicle group in oxycodone-dependent mice. Furthermore, AT-1001 had no significant effect on oxycodone-induced antinociception, as evaluated in the warm-water immersion assay.
CONCLUSION AND IMPLICATIONS: . Our findings suggest that AT-1001 effectively reduces oxycodone withdrawal signs without altering its antinociceptive effects. This supports α3β4⁎ partial agonists as promising candidates for further development as a safer and more comprehensive opioid withdrawal treatment.