Asis Joannes Luke B, Carampel Ajina C, Bacar Jariel Naomi B, Munar Johanna C, Gregorio Cynthia Grace C, Medina Paul Mark B, Dalmacio Leslie Michelle M, Sevilleja Jesus Emmanuel A D, Quirk Gregory J, Cena-Navarro Rohani
College of Medicine, University of the Philippines Manila, Manila, Philippines.
National Institute of Molecular Biology and Biotechnology, National Institutes of Health, University of the Philippines Manila, 623 Pedro Gil Street, Ermita, 1000, Manila, Philippines.
Psychopharmacology (Berl). 2025 Jun;242(6):1335-1349. doi: 10.1007/s00213-024-06731-5. Epub 2024 Dec 18.
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.
We assessed the behavioral effects during prolonged abstinence following repeated toluene inhalation in adolescent male and female rats.
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.
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.
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.
青少年吸入剂使用是一种研究不足且治疗不足的疾病，在女性中尤为如此。长期接触吸入剂，如甲苯，会对行为产生持久影响。然而，大多数动物研究缺乏对两性的纳入，且未关注禁欲期。
我们评估了青春期雄性和雌性大鼠反复吸入甲苯后长期禁欲期间的行为影响。
我们使用条件性位置偏好（CPP）程序，将青春期雄性和雌性Sprague Dawley大鼠反复暴露于甲苯蒸气（1500或3000 ppm）中6天。我们在禁欲的22天内测试了与药物相关的情境偏好、运动、焦虑样行为、物体记忆、社交偏好和认知灵活性。
在雌性中，3000 ppm甲苯在禁欲的第8天和第22天增加了CPP，但这种效应在雄性中未达到显著水平。相反，雄性在第7天和第21天运动显著增加。甲苯在长期禁欲期间也损害了社交新奇偏好和逆向学习，但未损害焦虑样行为或物体识别记忆。
我们在啮齿动物中的研究结果表明，女性吸入剂使用者在长期使用后的禁欲期间可能会表现出持续的药物偏好。此外，在青少年治疗方案中应解决长期的认知和社交缺陷问题。
