Effects of Estrogen and Cannabinoids on Learning

描述(由申请人提供) 越来越多的证据表明， 大麻的生物活性成分--三角洲9-四氢大麻酚 (Delta 9-THC)，以及中枢神经中的卵巢激素雌激素 系统。然而，目前关于这一事件的信息很少 这种相互作用对行为的功能性后果。此外，尽管 事实上，其他滥用药物的行为效果受到 雌性动物雌激素状态、Delta9-THC的行为效应 模型还没有被调查过。拟议研究中的实验将 检验以下假设：1)雌激素替代治疗将减弱 系统给药Delta9-THC对整体反应的干扰效应 去卵巢大鼠在多次刺激下反应的比率和百分比错误 重复获取的时间表和行为链的执行。2) 雌激素替代会不同程度地影响大麻素受体的水平 用定量受体放射自显影技术测量脑区的结合 与学习和记忆有关，并将增强大麻素的减少 长期应用Delta9-THC诱导的受体结合。3)雌激素 替代将加速Delta9-THC诱导的行为的发展 去卵巢大鼠对多个时序反应的耐受性 行为链的重复获得和表现。4)雌激素 更新换代将减弱 海马区注射Delta9-THC对小鼠的总有效率和 去卵巢大鼠在多个时间表下反应的误差百分比 行为链的重复获得和表现。这些结果将 第一次提供关于……互动效果的信息 雌激素和Delta9-THC对行为的影响。

DESCRIPTION (provided by applicant) There is growing evidence to indicate that there is an interaction between the biologically active constituent of marijuana, delta 9-tetrahydrocannabinol (delta 9-THC), and the ovarian hormone, estrogen, in the central nervous system. However, little information is currently available regarding the functional consequences of this interaction on behavior. Additionally, despite the fact that the behavioral effects of other drugs of abuse are influenced by estrogenic status, the behavioral effects of delta 9-THC in female animal models have not been investigated. The experiments in the proposed study will test the following hypotheses: 1) Estrogen replacement will attenuate the disruptive effects of systemically administered delta 9-THC on overall response rate and percent errors in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance of behavioral chains. 2) Estrogen replacement will differentially affect levels of cannabinoid receptor binding, as measured by quantitative receptor autoradiography, in brain areas implicated in learning and memory and will potentiate decreases in cannabinoid receptor binding induced by chronic administration of delta 9-THC. 3) Estrogen replacement will accelerate the development of delta 9-THC-induced behavioral tolerance in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance of behavioral chains. 4) Estrogen replacement will attenuate the disruptive effects of intrahippocampally-administered delta 9-THC on overall response rate and percent errors in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance of behavioral chains. These results will provide, for the first time, information regarding the interactive effects of estrogen and delta 9-THC on behavior.