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首页> 外文期刊>Addiction biology >Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status.
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Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status.

机译：Delta-9-四氢大麻酚在雌性大鼠中的长期行为和药效学效应取决于卵巢激素状态。

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Abuse of Delta-THC by females during adolescence may produce long-term deficits in complex behavioral processes such as learning, and these deficits may be affected by the presence of ovarian hormones. To assess this possibility, 40 injections of saline or 5.6 mg/kg of Delta-THC were administered i.p. daily during adolescence to gonadally intact or ovariectomized (OVX) female rats, yielding four treatment groups (intact/saline, intact/THC, OVX/saline, and OVX/ THC). Delta-THC (0.56-10 mg/kg) was then re-administered to each of the four groups during adulthood to examine their sensitivity to its disruptive effects. The behavioral task required adult subjects to both learn (acquisition component) different response sequences and repeat a known response sequence (performance component) daily. During baseline (no injection) and control (saline injection) sessions, OVX subjects had significantly higher response rates and lower percentages of error in both behavioral components than the intact groups irrespective of saline or Delta-THC administration during adolescence; the intact group that received Delta-THC had the lowest response rates in each component. Upon re-administration of Delta-THC, the groups that received adolescent ovariectomy alone, adolescent Delta-THC administration alone, or both treatments were found to be less sensitive to the rate-decreasing effects, and more sensitive to the error-increasing effects of Delta-THC than the control group (i.e. intact subjects that received saline during adolescence). Neurochemical analyses of the brains from each adolescent-treated group indicated that there were also persistent effects on cannabinoid type-1 (CB-1) receptor levels in the hippocampus and striatum that depended on the brain region and the presence of ovarian hormones. In addition, autoradiographic analyses of the brains from adolescent-treated, but behaviorally naive, subjects indicated that ovariectomy and Delta-THC administration produced effects on receptor coupling in some of the same brain regions. In summary, chronic administration of Delta-THC during adolescence in female rats produced long-term effects on operant learning and performance tasks and on the cannabinoid system that were mediated by the presence of ovarian hormones, and that altered their sensitivity to Delta-THC as adults.
机译：女性在青春期滥用Delta-THC可能会在复杂的行为过程（例如学习）中产生长期缺陷，并且这些缺陷可能会受到卵巢激素的影响。为了评估这种可能性，经腹膜内注射40次盐水或5.6 mg / kg Delta-THC。在青春期至性腺完整或卵巢切除（OVX）雌性大鼠每天进行一次，产生四个治疗组（完整/盐水，完整/ THC，OVX /盐水和OVX / THC）。然后在成年期对四组中的每组重新施用Delta-THC（0.56-10 mg / kg），以检查它们对其破坏作用的敏感性。行为任务要求成年受试者每天学习（获取组件）不同的响应序列并重复已知的响应序列（性能组件）。在基线（无注射）和对照（盐水注射）阶段，无论青春期服用生理盐水或Delta-THC，与完整组相比，OVX受试者的两种行为成分的应答率和错误率均显着降低。接受Delta-THC的完整人群在每个组件中的响应率最低。重新给予Delta-THC后，发现仅接受青春期卵巢切除术，单独接受青春期Delta-THC或同时接受这两种治疗的组对降速效果较不敏感，而对CRC的误差增大效果更敏感。 Delta-THC高于对照组（即完整的受试者在青春期期间接受盐水治疗）。对每个青少年治疗组的大脑进行神经化学分析表明，它们对海马和纹状体中的大麻素1型（CB-1）受体水平也有持续影响，这取决于大脑区域和卵巢激素的存在。此外，对经过青春期治疗但行为幼稚的受试者进行的放射自显影分析表明，卵巢切除术和Delta-THC给药对某些相同大脑区域的受体偶联产生影响。总之，在雌性大鼠青春期长期服用Delta-THC会对卵巢的激素介导的操作学习和执行任务以及大麻素系统产生长期影响，并改变了它们对Delta-THC的敏感性，大人。

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