Intravenous self-administration of delta-9-THC in adolescent rats produces long-lasting alterations in behavior and receptor protein expression.
Intravenous self-administration of delta-9-THC in adolescent rats produces long-lasting alterations in behavior and receptor protein expression.
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DOI：
10.1007/s00213-020-05684-9
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发表时间：
2021-01
影响因子：
3.4
通讯作者：
Torregrossa MM
中科院分区：
文献类型：
--
作者：
Stringfield SJ;Torregrossa MM
最初接触大麻素，包括Δ-9-四氢大麻酚（THC），通常发生在青春期。相当大的神经发育变化发生在整个青春期，外源性大麻素暴露造成的环境损害可能会改变自然发育轨迹。多项研究表明，青少年使用大麻会导致认知功能的长期缺陷，但这些影响的程度存在相当大的差异。我们试图建立一种新的程序来实现青少年大鼠静脉内THC自我管理，以确定青少年时期的THC摄入是否会产生成瘾相关行为的指数，改变成年期的工作记忆表现，或者改变与这些行为相关的蛋白质的表达。雄性和雌性青春期大鼠从PD 32-51开始学会了可操作地自我静脉内施用递增剂量的THC。在成年后，他们在禁欲的情况下进行了测试，以恢复THC寻求和工作记忆的延迟匹配样本任务。在一个单独的队列中，在多个脑区测量了多巴胺能、GABA能和大麻素受体蛋白的表达。男性和女性青少年自我管理的THC和表现出线索诱导的杠杆按下整个禁欲。暴露于THC的男性在成年期表现出轻微增强的工作记忆表现，更好的表现与青春期自我管理的总THC呈正相关。青少年THC暴露大鼠表现出减少CB 1，GABA和谷氨酸受体蛋白，主要是在前额叶皮层，背海马，腹侧被盖区。这些结果表明，自我管理剂量的THC暴露可以产生适度的行为和分子改变，包括对成年期工作记忆表现的性别依赖性影响。
Initial exposure to cannabinoids, including Δ-9-tetrahydrocannabinol (THC), often occurs during adolescence. Considerable neurodevelopmental alterations occur throughout adolescence, and the environmental insult posed by exogenous cannabinoid exposure may alter natural developmental trajectories. Multiple studies suggest that long-lasting deficits in cognitive function occur as a result of adolescent cannabis use, but considerable variability exists in the magnitude of these effects. We sought to establish a novel procedure for achieving intravenous THC self-administration in adolescent rats in order to determine if volitional THC intake in adolescence produced indices of addiction-related behavior, altered working memory performance in adulthood, or altered the expression of proteins associated with these behaviors across several brain regions. Male and female adolescent rats learned to operantly self-administer escalating doses of THC intravenously from PD 32–51. Upon reaching adulthood they were tested in abstinence for cued reinstatement of THC-seeking and working memory performance on a delayed-match-to-sample task. In a separate cohort, glutamatergic, GABAergic, and cannabinoid receptor protein expression was measured in multiple brain regions. Both male and female adolescents self-administered THC and exhibited cue-induced lever pressing throughout abstinence. THC exposed males exhibited slightly enhanced working memory performance in adulthood, and better performance positively correlated with total THC self-administered during adolescence. Adolescent THC-exposed rats exhibited reductions in CB1, GABA and glutamate receptor protein, primarily in the prefrontal cortex, dorsal hippocampus, and ventral tegmental area. These results suggest that THC exposure at self-administered doses can produce moderate behavioral and molecular alterations, including sex-dependent effects on working memory performance in adulthood.
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影响因子：
5.6
作者：
Ellgren, M.;Artmann, A.;Tkalych, O.;Gupta, A.;Hansen, H. S.;Hansen, S. H.;Devi, L. A.;Hurd, Y. L.
通讯作者：
Hurd, Y. L.
影响因子：
5
作者：
Braida, D;Pozzi, M;Sala, M
通讯作者：
Sala, M
影响因子：
7.3
作者：
Gunasekaran, N.;Long, L. E.;McGregor, I. S.
通讯作者：
McGregor, I. S.
影响因子：
7.3
作者：
Burston, James J.;Wiley, Jenny L.;Sim-Selley, Laura J.
通讯作者：
Sim-Selley, Laura J.
影响因子：
3.6
作者：
Justinova, Z;Goldberg, SR;Tanda, G
通讯作者：
Tanda, G