Effects of Chronic THC in Adolescence

慢性 THC 对青春期的影响

• 批准号: 7033700
• 负责人: PETER J WINSAUER
• 金额: $ 25.12万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2011-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7033700
• 关键词: brain; cannabinoids; drug abuse; female; learning

DESCRIPTION (provided by applicant): Drug abuse by an individual during adolescence, a significant period of maturation, may enhance their vulnerability to the central nervous system (CNS) effects of abused drugs. The present application brings together a multidisciplinary team of investigators to examine whether pharmacodynamic changes resulting from the presence of ovarian hormones and chronic A9-THC administration alters the subjective effects of the drug, increases the vulnerability of females to drug abuse, and changes their ability to learn. Chronic exposure to A9-THC is of particular interest because this illicit drug is widely abused by adolescents, while the presence or absence of ovarian hormones is of interest as a cofactor because: 1) ovarian hormones may have independent or interactive influences on maturation and 2) published data generated by these investigators indicate that the ovarian hormone estrogen can attenuate the detrimental effects of A9- THC on learning in female rats and alter the binding of cannabinoid ligands in brain areas that are critical for learning such as the hippocampus. For these same reasons, and because there is a paucity of data regarding the effects of A9- THC using female models, all of the planned behavioral experiments will use female rats and involve the presence or absence of ovarian hormones in A9-THC-treated subjects. In addition, subjects in each behavioral group will be sacrificed to examine potential changes in cannabinoid receptors and endogenous cannabinoid levels in relevant brain areas. More specifically, the aims of this grant will determine whether: 1) peri-adolescent A9-THC administration in gonadally intact female rats will alter their sensitivity as adults to the acute behavioral effects of A9-THC when compared to either gonadally intact or ovariectomized females that were drug-naive during adolescence; 2) peri-adolescent A9- THC administration in gonadally intact female rats will alter the pharmacodynamic response of the cannabinoid system to acute challenge with A9-THC as an adult when compared to either gonadally intact or ovariectomized females that were drug-naive during adolescence; 3) A9-THC administration from adolescence to adulthood in gonadally intact female rats will produce effects on learning that are different from those produced in either gonadally intact or ovariectomized females whose chronic administration of A9-THC did not start until post adolescence; and 4) A9-THC administration from adolescence to adulthood in gonadally intact female rats will alter the endogenous response of the cannabinoid system when compared to either gonadally intact or ovariectomized females whose chronic administration of A9-THC did not start until post adolescence. Together, data from these experiments will demonstrate how drug abuse and hormonal status during adolescence may permanently alter brain function and the liability of subsequent abuse of A9-THC.

描述（由申请人提供）：在青春期中，一个人滥用药物，这是一个重要的成熟时期，可能会增强其对中枢神经系统（CNS）滥用药物的脆弱性。本应用程序汇集了一个多学科研究人员的团队，以检查卵巢激素和慢性A9-THC给药引起的药效变化是否改变了药物的主观影响，增加了女性对药物滥用的脆弱性，并改变了学习能力。 Chronic exposure to A9-THC is of particular interest because this illicit drug is widely abused by adolescents, while the presence or absence of ovarian hormones is of interest as a cofactor because: 1) ovarian hormones may have independent or interactive influences on maturation and 2) published data generated by these investigators indicate that the ovarian hormone estrogen can attenuate the detrimental effects of A9- THC on learning in female大鼠并改变了大脑区域中大麻素配体的结合，这对于海马诸如学习至关重要。由于这些相同的原因，并且由于使用女性模型的A9-THC影响的数据很少，因此所有计划的行为实验都将使用女性大鼠，并且涉及A9-THC治疗的受试者中的卵巢激素。此外，将牺牲每个行为组中的受试者，以检查相关大脑区域中大麻素受体和内源性大麻素水平的潜在变化。更具体地说，这笔赠款的目的将确定：1）在性腺完整的女性大鼠中，在雌性大鼠中给药是否会改变其成年人对A9-thc急性行为影响的敏感性，而与性腺完整或卵巢完整的雌性相比，在青春期期间是毒品。 2）在性腺完整的雌性大鼠中给药的围场A9-THC会改变大麻素系统对与A9-THC急性挑战的药物动力学反应，而与性腺完整或卵巢骨切除的女性相比，在青春期期间是药物不佳的女性； 3）从青春期到成年雌性大鼠的A9-THC给药会对学习产生与性腺完整或卵巢切除型女性不同的学习作用，其长期给予A9-THC的雌性直到青春期才开始。 4）与性腺完整的雌性大鼠的A9-THC给药，从青春期到成年的雌性大鼠在成年后会改变大麻素系统的内源性反应，而与性腺完整或卵巢切除的女性相比，其长期为A9-THC的妇女的A9-THC持续到青春期后才开​​始。总之，这些实验的数据将证明青春期药物滥用和激素状态如何永久改变大脑功能以及随后滥用A9-THC的责任。