Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status.
Long-term behavioral and pharmacodynamic effects of delta-9-tetrahydrocannabinol in female rats depend on ovarian hormone status.
复制标题
δ-9-四氢大麻酚对雌性大鼠的长期行为和药效学影响取决于卵巢激素状态。
DOI：
10.1111/j.1369-1600.2010.00227.x
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发表时间：
2011
影响因子：
3.4
通讯作者：
Sutton,JessieL
中科院分区：
文献类型：
--
作者：
Winsauer,PeterJ;Daniel,JillM;Filipeanu,CatalinM;Leonard,StuartT;Hulst,JerielleL;Rodgers,ShaefaliP;Lassen-Greene,CarolineL;Sutton,JessieL
女性在青春期滥用Δ9-THC可能会在学习等复杂的行为过程中产生长期缺陷，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，在青春期期间，对性腺完整或卵巢切除（OVX）的雌性大鼠每天腹膜内注射40次生理盐水或5.6 mg/kg Δ9-THC，产生4个处理组（完整/生理盐水、完整/THC、OVX/生理盐水和OVX/THC）。 然后在成年期对四组中的每一组重新给予Δ9-THC（0.56-10 mg/kg），以检查它们对其破坏性影响的敏感性。行为任务要求成年受试者学习（获取组件）不同的反应序列和重复一个已知的反应序列（性能组件）每天。在基线（无注射）和对照（盐水注射）阶段，OVX受试者在两个行为组成部分中的应答率显著高于完整组，而错误百分比较低，无论青春期期间是否给予盐水或Δ9-THC;接受Δ9-THC的完整组在每个组成部分中的应答率最低。再次给予Δ9-THC后，发现仅接受青少年卵巢切除术、仅接受青少年Δ9-THC给药或接受两种治疗的组对Δ9-THC的速率降低效应不太敏感，对Δ9-THC的误差增加效应比对照组（即在青春期接受生理盐水的完整受试者）更敏感。对每个青少年治疗组大脑的神经化学分析表明，海马和纹状体中的大麻素1型（CB-1）受体水平也存在持续影响，这取决于大脑区域和卵巢激素的存在。此外，对青少年接受治疗但行为幼稚的受试者的大脑进行放射自显影分析表明，卵巢切除术和Δ9-THC给药对某些相同脑区域的受体偶联产生了影响。总之，在青春期长期给予雌性大鼠Δ9-THC对操作性学习和表现任务以及大麻素系统产生了长期影响，这些影响是由卵巢激素介导的，并且改变了它们对Δ9-THC的敏感性。
Abuse of Δ9‐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 Δ9‐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). Δ9‐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 Δ9‐THC administration during adolescence; the intact group that received Δ9‐THC had the lowest response rates in each component. Upon re‐administration of Δ9‐THC, the groups that received adolescent ovariectomy alone, adolescent Δ9‐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 Δ9‐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 naïve, subjects indicated that ovariectomy and Δ9‐THC administration produced effects on receptor coupling in some of the same brain regions. In summary, chronic administration of Δ9‐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 Δ9‐THC as adults.