Repeated toluene inhalation in male and female adolescent rats induces persistent drug preference and impairs cognitive and social behavior.

IF 3.5 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2024-12-18 DOI:10.1007/s00213-024-06731-5

Joannes Luke B Asis, Ajina C Carampel, Jariel Naomi B Bacar, Johanna C Munar, Cynthia Grace C Gregorio, Paul Mark B Medina, Leslie Michelle M Dalmacio, Jesus Emmanuel A D Sevilleja, Gregory J Quirk, Rohani Cena-Navarro

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引用次数: 0

Abstract

Rationale: Adolescent inhalant use is an understudied and undertreated disorder, particularly in females. Chronic exposure to inhalants, like toluene, can have long-lasting effects on behavior. However, most animal studies lack the incorporation of both sexes and do not focus on the abstinence period.

Objective: We assessed the behavioral effects during prolonged abstinence following repeated toluene inhalation in adolescent male and female rats.

Methods: We repeatedly exposed adolescent male and female Sprague Dawley rats to toluene vapor (1500 or 3000 ppm) for 6 days using the conditioned place preference (CPP) procedure. We tested drug-associated context preference, locomotion, anxiety-like behavior, object memory, social preference, and cognitive flexibility across 22 days of abstinence.

Results: In females, 3000 ppm toluene increased CPP on days 8 and 22 of abstinence but this effect did not reach significance in males. Instead, males showed a significant increase in locomotion on days 7 and 21. Toluene also impaired social novelty preference and reversal learning during long-term abstinence, but not anxiety-like behavior or object recognition memory.

Conclusions: Our rodent findings suggest that female inhalant users may show persistent drug preference during abstinence following chronic use. Furthermore, prolonged cognitive and social deficits should be addressed in treatment programs for adolescents.

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雄性和雌性青春期大鼠反复吸入甲苯可诱导持续的药物偏好并损害认知和社会行为。

理由：青少年吸入剂使用是一种研究不足和治疗不足的疾病，特别是在女性中。长期接触吸入剂，如甲苯，会对行为产生长期影响。然而，大多数动物研究缺乏两性的结合，也没有关注禁欲期。目的：评价青春期雌雄大鼠反复吸入甲苯后长期戒断行为的影响。方法：采用条件位置偏好（CPP）方法，将青春期雄性和雌性大鼠反复暴露于甲苯蒸气（1500或3000 ppm）中6天。在22天的戒断期间，我们测试了与药物相关的情境偏好、运动、焦虑样行为、对象记忆、社会偏好和认知灵活性。结果：3000 ppm甲苯使雌性小鼠戒断第8天和第22天的CPP升高，但对雄性小鼠无显著影响。相反，雄鼠在第7天和第21天的活动量显著增加。甲苯还会损害长期戒断期间的社会新奇偏好和反转学习，但不会损害焦虑样行为或物体识别记忆。结论：我们的啮齿动物研究结果表明，女性吸入剂使用者在长期使用后戒断期间可能表现出持续的药物偏好。此外，长期的认知和社会缺陷应该在青少年的治疗方案中加以解决。

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

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.