Impact of morphine dependence and withdrawal on economic demand for fentanyl, cocaine, and methamphetamine in rats

IF 3.5 2区医学 Q1 PSYCHIATRY

Drug and alcohol dependence Pub Date : 2026-01-01 Epub Date: 2025-11-28 DOI:10.1016/j.drugalcdep.2025.112992

Robert W. Seaman Jr. , Nima Shariatzadeh , Kelly A. Salinas , Christina M. George , Yong-Gong Shi , Gregory T. Collins

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引用次数: 0

Abstract

Background

Stimulant-opioid co-use has surged in the United States, with methamphetamine use among people who use opioids increasing 82.6 % from 2015 to 2017. This trend contributes to rising overdose deaths, marking a "fourth wave" of the opioid epidemic. This study examined how opioid dependence and withdrawal affect the reinforcing effects of opioids and stimulants.

Methods & results

Male Sprague-Dawley rats (8–12 per group) were trained to self-administer fentanyl (3.2 µg/kg/inf), cocaine (0.32 mg/kg/inf), or methamphetamine (0.1 mg/kg/inf) under fixed ratio (FR) schedules. Opioid dependence was established through escalating twice-daily morphine injections (10–40 mg/kg) over four days, then maintained with daily doses of 40 mg/kg morphine. Rats exhibited stable signs of withdrawal (somatic signs, weight loss, hyperalgesia) following 20 h but not 12 h of morphine deprivation. Demand curves were generated by progressively increasing work requirements (FR 3, 5, 10, 18, 32, 56, 100, etc.) across sessions conducted 12 (morphine dependent) or 20 (morphine withdrawn) hours after morphine or saline (non-dependent controls). Morphine withdrawal (20-hour deprived group) increased demand for fentanyl but decreased demand for cocaine and methamphetamine. Morphine dependence (12-hour deprived group) had minimal effects, but did reliably decrease demand for cocaine. Morphine dependence increased demand intensity (Q₀) only for the small dose of fentanyl; all other conditions were unaffected.

Conclusions

These results demonstrate that opioid withdrawal increases motivation for opioid use while reducing motivation for stimulants, particularly at higher costs. Understanding these dynamics is crucial for developing effective polysubstance treatments addressing both opioid dependence and stimulant co-use.

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吗啡依赖和戒断对大鼠芬太尼、可卡因和甲基苯丙胺经济需求的影响

在美国，兴奋剂和阿片类药物的共同使用激增，从2015年到2017年，阿片类药物使用者中甲基苯丙胺的使用量增加了82.6%。这一趋势导致过量死亡人数上升，标志着阿片类药物流行的“第四波”。本研究探讨了阿片类药物依赖和戒断如何影响阿片类药物和兴奋剂的强化作用。方法和结果雄性Sprague-Dawley大鼠（每组8-12只）在固定比例（FR）计划下自我给药芬太尼（3.2µg/kg/inf）、可卡因（0.32 mg/kg/inf）或甲基苯丙胺（0.1 mg/kg/inf）。阿片类药物依赖是通过在4天内逐步增加每日两次吗啡注射（10-40 mg/kg），然后维持每日剂量40 mg/kg吗啡来建立的。大鼠在吗啡剥夺20小时后表现出稳定的戒断症状（躯体症状、体重减轻、痛觉过敏），而在12小时后则没有。需求曲线是通过在吗啡或生理盐水（非依赖对照）后12小时（吗啡依赖）或20小时（吗啡戒断）期间逐渐增加的工作需求（FR 3、5、10、18、32、56、100等）而产生的。吗啡戒断（剥夺20小时组）增加了对芬太尼的需求，但减少了对可卡因和甲基苯丙胺的需求。吗啡依赖（12小时剥夺组）影响最小，但确实减少了对可卡因的需求。吗啡依赖仅对小剂量芬太尼增加需求强度（Q0）；其他条件均未受影响。这些结果表明，阿片类药物戒断增加了阿片类药物使用的动机，同时减少了兴奋剂的动机，特别是在成本较高的情况下。了解这些动态对于开发有效的多物质治疗解决阿片类药物依赖和兴奋剂共同使用至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug and alcohol dependence 医学-精神病学

CiteScore

7.40

自引率

7.10%

发文量

409

审稿时长

41 days

期刊介绍： Drug and Alcohol Dependence is an international journal devoted to publishing original research, scholarly reviews, commentaries, and policy analyses in the area of drug, alcohol and tobacco use and dependence. Articles range from studies of the chemistry of substances of abuse, their actions at molecular and cellular sites, in vitro and in vivo investigations of their biochemical, pharmacological and behavioural actions, laboratory-based and clinical research in humans, substance abuse treatment and prevention research, and studies employing methods from epidemiology, sociology, and economics.