A novel tramadol-polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study.

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES
Behavioural Pharmacology Pub Date : 2024-08-01 Epub Date: 2024-06-17 DOI:10.1097/FBP.0000000000000778
Shaimaa A Elshebiney, Rania A Elgohary, Marwa E El-Shamarka, Mostafa Mabrouk, Hanan H Beheri
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引用次数: 0

Abstract

Drug dependence is a chronic brain disease characterized by craving and recurrent episodes of relapse. Tramadol HCl is a promising agent for withdrawal symptoms management, considering its relatively low abuse potential and safety. Oral administration, however, is not preferred in abstinence maintenance programs. Introducing an implantable, long-lasting formula is suggested to help outpatient abstinence programs achieve higher rates of treatment continuation. Tramadol implants (T350 and T650) were prepared on polycaprolactone polymer ribbons by the wet method. Male Wistar rats were adapted to heroin-conditioned place preference (CPP) at escalating doses (3-30 mg/kg, intraperitoneally, for 14 days). Implants were surgically implanted in the back skin of rats. After 14 days, the CPP score was recorded. Naloxone (1 mg/kg, intraperitoneally) was used to induce withdrawal on day 15, and symptoms were scored. Elevated plus maze and open field tests were performed for anxiety-related symptoms. Striata were analyzed for neurochemical changes reflected in dopamine, 3,4-dihydroxyphenyl acetic acid, gamma-aminobutyric acid, and serotonin levels. Brain oxidative changes including glutathione and lipid peroxides were assessed. The tramadol implants (T350 and T650) reduced heroin CPP and limited naloxone-induced withdrawal symptoms. The striata showed increased levels of 3,4-dihydroxyphenyl acetic acid, and serotonin and decreased levels of gamma-aminobutyric acid and dopamine after heroin withdrawal induction, which were reversed after implanting T350 and T650. Implants restore the brain oxidative state. Nonsignificant low naloxone-induced withdrawal score after the implant was used in naive subjects indicating low abuse potential of the implants. The presented tramadol implants were effective at diminishing heroin CPP and withdrawal in rats, suggesting further investigations for application in the management of opioid withdrawal.

一种新型曲马多-聚己内酯植入物可缓解大鼠的海洛因条件性位置偏好和戒断:行为和神经化学研究。
药物依赖是一种慢性脑部疾病,其特点是渴求和反复复发。考虑到盐酸曲马多的滥用可能性相对较低且安全性高,它是一种很有前景的戒断症状控制药物。然而,在戒断维持计划中,口服给药并不是首选。建议引入一种可植入的长效配方,以帮助门诊戒断计划实现更高的持续治疗率。采用湿法在聚己内酯聚合物带上制备曲马多植入剂(T350 和 T650)。雄性 Wistar 大鼠以递增剂量(3-30 毫克/千克,腹腔注射,14 天)适应海洛因条件性场所偏好(CPP)。植入物通过手术植入大鼠背部皮肤。14 天后,记录 CPP 评分。第 15 天使用纳洛酮(1 毫克/千克,腹腔注射)诱导戒断,并对症状进行评分。对焦虑相关症状进行高架加迷宫和开阔地测试。分析纹状体的神经化学变化,以反映多巴胺、3,4-二羟基苯乙酸、γ-氨基丁酸和血清素的水平。还对包括谷胱甘肽和脂质过氧化物在内的大脑氧化变化进行了评估。曲马多植入物(T350和T650)降低了海洛因的CPP,并限制了纳洛酮诱发的戒断症状。植入 T350 和 T650 后,海洛因戒断诱导的纹状体中 3,4-二羟基苯乙酸和血清素水平升高,γ-氨基丁酸和多巴胺水平降低。植入物可恢复大脑氧化状态。在天真的受试者中使用植入物后,纳洛酮诱导的戒断评分并不显著降低,这表明植入物的滥用可能性较低。所展示的曲马多植入物能有效降低大鼠的海洛因CPP和戒断率,建议进一步研究其在阿片类药物戒断管理中的应用。
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来源期刊
Behavioural Pharmacology
Behavioural Pharmacology 医学-行为科学
CiteScore
3.40
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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