Aguilar María A, Ledesma Juan Carlos, Rodríguez-Arias Marta, Penalva Carles, Manzanedo Carmen, Miñarro José, Arenas M Carmen
Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain.
Int J Mol Sci. 2017 Jun 21;18(6):1326. doi: 10.3390/ijms18061326.
Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause psychiatric symptoms, such as psychosis, cognitive impairment, anxiety, and depression. The aim of the present research was to study the consequences of adolescent exposure to cannabis on the psychiatric-like effects promoted by cocaine withdrawal in adult mice. We pre-treated juvenile mice with the cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) and then subjected them to a chronic cocaine treatment during adulthood. Following these treatments, animals were tested under cocaine withdrawal in the following paradigms: pre-pulse inhibition, object recognition, elevated plus maze, and tail suspension. The long-term psychotic-like actions induced by WIN were not modified after cocaine cessation. Moreover, the memory impairments induced by cocaine withdrawal were not altered by previous adolescent WIN intake. However, WIN pre-treatment prevented the anxiogenic effects observed after cocaine abstinence, and led to greater depressive-like symptoms following cocaine removal in adulthood. This study is the first to show the long-lasting behavioral consequences of juvenile exposure to WIN on cocaine withdrawal in adult mice.
长期吸食大麻在青少年中是一种越来越普遍的行为，并且已被证明会导致持久的神经行为改变。此外，已经证实成年期的可卡因成瘾与青少年时期的大麻滥用高度相关。吸食可卡因以及随后的戒断会引发精神症状，如精神病、认知障碍、焦虑和抑郁。本研究的目的是探究青少年接触大麻对成年小鼠可卡因戒断所引发的类似精神症状的影响。我们用大麻素CB1受体激动剂WIN 55212-2（WIN）对幼年小鼠进行预处理，然后在成年期对它们进行慢性可卡因治疗。经过这些处理后，在以下范式下对动物进行可卡因戒断测试：前脉冲抑制、物体识别、高架十字迷宫和悬尾实验。WIN诱导的长期类似精神病的行为在可卡因戒断后并未改变。此外，可卡因戒断引起的记忆障碍也不会因青少年时期预先摄入WIN而改变。然而，WIN预处理可预防可卡因戒断后观察到的焦虑效应，并在成年期可卡因戒断后导致更严重的类似抑郁的症状。本研究首次表明幼年接触WIN对成年小鼠可卡因戒断具有持久的行为影响。
