Effects of Chronic THC in Adolescence

慢性 THC 对青春期的影响

• 批准号: 7584103
• 负责人: PETER J WINSAUER
• 金额: $ 23.74万
• 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 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7584103
• 关键词: Acute; Address; Adolescence; Adolescent; Adult; Affect; Anus; Area; Attenuated; Behavioral; Binding; Birds; Brain; Cannabinoids; Chronic; Data; Drug abuse; Endocannabinoids; Estrogens; Exposure to; Female; Grant; Hippocampus (Brain); Hormonal; Human; Illicit Drugs; Individual; Learning; Ligands; Modeling; Neuraxis; Oral; Ovarian hormone; Pharmaceutical Preparations; Pharmacodynamics; Property; Publishing; Rattus; Research Personnel; Staging; System; Testing; Tetrahydrocannabinol; Treatment Protocols; Upper arm; cannabinoid receptor; cofactor; drug of abuse; interest; multidisciplinary; postnatal; prevent; programs; receptor binding; research study; response

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-THG 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-naTve 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-naTve 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.

在青春期中，个人滥用毒品，很重要的成熟时期，可能会增强其脆弱性 滥用药物的中枢神经系统（CNS）作用。本应用程序汇集了一个多学科 研究人员团队检查是否存在卵巢激素的药效学变化 慢性A9-THC给药改变了药物的主观影响，增加了女性的脆弱性 滥用药物，并改变他们的学习能力。长期暴露于A9-THG是特别感兴趣的，因为这种非法 药物被青少年广泛滥用，而卵巢激素的存在或不存在作为辅助因子感兴趣 因为：1）卵巢激素可能对成熟的独立或互动影响，2）已发布数据 这些研究者产生的表明，卵巢激素雌激素可以减弱A9- 关于雌性大鼠学习的THC并改变大脑区域中大麻素配体的结合，这对于学习至关重要 例如海马。由于这些相同的原因，并且因为关于A9的影响的数据很少 THC使用女性模型，所有计划的行为实验都将使用女性大鼠，并涉及存在或 A9-THC处理的受试者缺乏卵巢激素。此外，每个行为组中的受试者将是 牺牲是为了检查相关大脑中大麻素受体和内源性大麻素水平的潜在变化 区域。更具体地说，这笔赠款的目的将确定是否：1） Gonadally完整的雌性大鼠比较成年人对A9-THC的急性行为影响的敏感性会改变其敏感性 在青春期期间是卵巢的雌性或卵巢切除的女性； 2）青春期A9- 性腺完整雌性大鼠的THC给药将改变大麻素系统的药效反应 与性腺完整或卵巢切除的女性相比，A9-THC急性挑战是成年人的 是青春期的药物； 3）从青春期到成年的A9-THC给药 雌性大鼠会对学习产生影响，而雌性大鼠与性腺完好无损或 卵巢切除的雌性长期施用A9-THC直到青春期才开始。 4）A9-THC 从青春期到成年的雌性大鼠的给药将改变 大麻素系统与性腺完整或卵巢切除的女性相比，其长期给药 a9-thc的做法 - 从未开始直到青春期后。.一起，这些实验的数据将证明药物如何 青春期期间的滥用和激素状态可能会永久改变大脑功能和随后的责任 滥用A9-THC。