在寻求-摄取连锁强化计划中,急性尼古丁给药会降低惩罚在抑制瑞芬太尼消耗方面的效果。

IF 3.5 3区 医学 Q2 NEUROSCIENCES
Psychopharmacology Pub Date : 2024-10-01 Epub Date: 2024-05-22 DOI:10.1007/s00213-024-06613-w
Sarah C Honeycutt, David D Lichte, Elizabeth A Gilles-Thomas, Ashmita Mukherjee, Gregory C Loney
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引用次数: 0

摘要

理由:尼古丁依赖与阿片类药物使用障碍(OUDs)高度合并。使用含尼古丁的产品会增加滥用处方阿片类药物的倾向,同时解决尼古丁和阿片类药物的使用问题比单独治疗阿片类药物的使用问题对治疗 OUDs 更有效:鉴于这种极端的合并症,有必要进一步阐明尼古丁作为促进易患 OUDs 的因素的影响。在此,我们试图进一步探讨尼古丁给药对瑞芬太尼(RMF)操作性自我给药的影响,瑞芬太尼是一种快速起效的合成μ-阿片受体激动剂,我们采用了一种异质的寻求-摄取连锁强化计划,在无惩罚和有惩罚的条件下进行强化:雄性和雌性大鼠在操作性自我给药前接受尼古丁(0.4 毫克/千克)或生理盐水。这些环节包括按下 "寻找 "杆以获得 "服用 "杆,按下 "服用 "杆可获得 3.2 µg/kg RMF。习得后,继续寻求/服用药物会受到脚震的惩罚:结果:相对于生理盐水,尼古丁增加了RMF的消耗量。此外,尼古丁处理导致大鼠的寻药反应和完成的循环次数显著增加,而且这种效应在惩罚过程中变得更加明显,因为尼古丁处理的大鼠对RMF寻药的抑制作用显著低于对照组。尼古丁处理在功能上降低了脚震惩罚对阿片类药物寻求的威慑效果:结论:尼古丁的施用增强了大鼠对RMF的食欲反应和消耗反应,并产生了对RMF的惩罚不敏感表型,这种表型受脚震惩罚的影响较小。这些发现进一步支持了尼古丁会增加阿片类药物成瘾行为脆弱性的假说。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Acute nicotine administration reduces the efficacy of punishment in curbing remifentanil consumption in a seeking-taking chain schedule of reinforcement.

Acute nicotine administration reduces the efficacy of punishment in curbing remifentanil consumption in a seeking-taking chain schedule of reinforcement.

Rationale: Nicotine dependence is highly comorbid with opioid use disorders (OUDs). The use of nicotine-containing products increases the propensity to misuse prescription opioids and addressing both nicotine and opioid use simultaneously is more efficacious for treatment of OUDs than treating opioid use alone.

Objectives: Given this extreme comorbidity, further elucidation of the effects of nicotine as a factor in promoting vulnerability to development of OUDs is needed. Here, we sought to further explore the effects of nicotine administration on operant self-administration of remifentanil (RMF), a fast-acting synthetic µ-opioid receptor agonist, using a heterogenous seeking-taking chain schedule of reinforcement in unpunished and punished conditions.

Methods: Male and female rats received nicotine (0.4 mg/kg) or saline prior to operant self-administration sessions. These sessions consisted of pressing a 'seeking' lever to gain access to a 'taking' lever that could be pressed for delivery of 3.2 µg/kg RMF. After acquisition, continued drug seeking/taking was punished through contingent delivery of foot-shock.

Results: Nicotine, relative to saline, increased RMF consumption. Furthermore, nicotine treatment resulted in significantly higher seeking responses and cycles completed, and this effect became more pronounced during punished sessions as nicotine-treated rats suppressed RMF seeking significantly less than controls. Nicotine treatment functionally reduced the efficacy of foot-shock punishment as a deterrent of opioid-seeking.

Conclusions: Nicotine administration enhanced both appetitive and consummatory responding for RMF and engendered a punishment-insensitive phenotype for RMF that was less impacted by contingent administration of foot-shock punishment. These findings provide further support for the hypothesis that nicotine augments vulnerability for addiction-like behaviors for opioids.

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来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
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.
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