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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Ovarian hormones and chronic administration during adolescence modify the discriminative stimulus effects of delta-9-tetrahydrocannabinol (Δ 9-THC) in adult female rats
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Ovarian hormones and chronic administration during adolescence modify the discriminative stimulus effects of delta-9-tetrahydrocannabinol (Δ 9-THC) in adult female rats

机译：卵巢激素和青春期的长期服用改变成年雌性大鼠的delta-9-tetrahydrocannabinol（Δ9-THC）的歧视性刺激作用

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Marijuana abuse during adolescence may alter its abuse liability during adulthood by modifying the interoceptive (discriminative) stimuli produced, especially in females due to an interaction with ovarian hormones. To examine this possibility, either gonadally intact or ovariectomized (OVX) female rats received 40 intraperitoneal injections of saline or 5.6 mg/kg of Δ 9-THC daily during adolescence, yielding 4 experimental groups (intact/saline, intact/Δ 9-THC, OVX/saline, and OVX/Δ 9-THC). These groups were then trained to discriminate Δ 9-THC (0.32-3.2 mg/kg) from saline under a fixed-ratio (FR) 20 schedule of food presentation. After a training dose was established for the subjects in each group, varying doses of Δ 9-THC were substituted for the training dose to obtain dose-effect (generalization) curves for drug-lever responding and response rate. The results showed that: 1) the OVX/saline group had a substantially higher mean response rate under control conditions than the other three groups, 2) both OVX groups had higher percentages of THC-lever responding than the intact groups at doses of Δ 9-THC lower than the training dose, and 3) the OVX/Δ 9-THC group was significantly less sensitive to the rate-decreasing effects of Δ 9-THC compared to other groups. Furthermore, at sacrifice, western blot analyses indicated that chronic Δ 9-THC in OVX and intact females decreased cannabinoid type-1 receptor (CB1R) levels in the striatum, and decreased phosphorylation of cyclic adenosine monophosphate response element binding protein (p-CREB) in the hippocampus. In contrast to the hippocampus, chronic Δ 9-THC selectively increased p-CREB in the OVX/saline group in the striatum. Extracellular signal-regulated kinase (ERK) was not significantly affected by either hormone status or chronic Δ 9-THC. In summary, these data in female rats suggest that cannabinoid abuse by adolescent human females could alter their subsequent responsiveness to cannabinoids as adults and have serious consequences for brain development.
机译：青春期滥用大麻可通过改变所产生的感受性（歧视性）刺激来改变其成年期的滥用责任，特别是在女性中，由于与卵巢激素的相互作用。为了检验这种可能性，在青春期每天接受40次性腺切除或卵巢切除（OVX）的雌性大鼠腹膜内注射生理盐水或5.6 mg / kgΔ9-THC，产生4个实验组（完整/盐水，完整/Δ9-THC） ，OVX /盐水和OVX /Δ9-THC）。然后对这些组进行训练，以按照固定比例（FR）20的食物提示时间表从盐水中区分Δ9-THC（0.32-3.2 mg / kg）。在为每组中的受试者确定训练剂量后，将不同剂量的Δ9-THC替换为训练剂量，以获得药物杠杆反应和反应率的剂量效应（一般化）曲线。结果表明：1）在对照条件下，OVX /盐水组的平均应答率明显高于其他三组; 2）在剂量为Δ9的情况下，两个OVX组的THC应答率均高于完整组-THC低于训练剂量，并且3）与其他组相比，OVX /Δ9-THC组对Δ9-THC的降速作用的敏感性明显降低。此外，在牺牲时，蛋白质印迹分析表明，OVX和完整雌性中的慢性Δ9-THC降低了纹状体中大麻素1型受体（CB1R）的水平，并降低了环磷酸腺苷单磷酸反应元件结合蛋白（p-CREB）的磷酸化在海马中。与海马不同，慢性Δ9-THC在纹状体的OVX /生理盐水组中选择性增加p-CREB。细胞外信号调节激酶（ERK）不受激素状态或慢性Δ9-THC的影响。总之，雌性大鼠的这些数据表明，青春期人类雌性滥用大麻可能会改变其对成年后对大麻素的反应，并对脑发育产生严重后果。

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