Interactive Effects of Cannabinoids and Sex Hormones in Females

大麻素和性激素对女性的相互作用

• 批准号: 8827986
• 负责人: PETER J WINSAUER
• 金额: $ 32.04万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8827986
• 关键词: ATP phosphohydrolase; Acquired Immunodeficiency Syndrome; Acute; Address; Adolescence; Adult; Affect; Age; Animals; Area; Attenuated; Behavioral; Binding; Brain; Brain-Derived Neurotrophic Factor; CREB-binding protein; CREB1 gene; Cachexia; Cannabinoids; Chronic; Complex; Complication; Corpus striatum structure; Cyclic AMP; Data; Development; Disease; District of Columbia; Estradiol; Estrogen Receptors; Estrogens; Female; General Population; Genetic Transcription; Glaucoma; Goals; Gonadal Steroid Hormones; Grant; Health; Heat-Shock Response; Hippocampus (Brain); Homologous Gene; Hormones; Illicit Drugs; Learning; Ligands; Long-Term Effects; Malignant Neoplasms; Marijuana; Marijuana Smoking; Medical; Memory; Memory impairment; Molecular; Molecular Chaperones; Multiple Sclerosis; Neuronal Plasticity; Ovarian hormone; Pharmaceutical Preparations; Play; Process; Proteins; Proteomics; Publishing; Rattus; Receptor Signaling; Reporting; Research; Research Personnel; Response Elements; Risk; Role; Signal Transduction; Signaling Protein; Site; Surveys; Synapses; Synaptic plasticity; Testing; Tetrahydrocannabinol; Therapeutic; Therapeutic Uses; Time; Work; attenuation; behavioral study; cannabinoid receptor; cofactor; cognitive function; critical period; drug of abuse; human CREBBP protein; interest; marijuana use; memory encoding; memory process; multidisciplinary; palliative; public health relevance; receptor; receptor sensitivity; research study; restoration; sex

DESCRIPTION (provided by applicant): Recent surveys have indicated that the rate of use of marijuana among the general population has increased to as high as 7%. Moreover, marijuana has now been legalized in 18 states and the District of Columbia for medical purposes, which has contributed to the notion that this illicit drug may pose the least health-related risks. This has not been verified, however, and there is a real need to understand all of the biomedical consequences of cannabinoid use and abuse. The present application brings together a multidisciplinary team of investigators to examine whether the presence of ovarian hormones and acute or chronic 9- tetrahydrocannabinol ( 9-THC) administration reduces memory deficits in females. Chronic administration of 9-THC is of particular interest because this illici drug is widely abused chronically and most of the potential therapeutic uses may also require chronic administration. The presence or absence of ovarian hormones is of interest as a cofactor because: 1) ovarian hormones have direct and indirect influences on cognitive function, and 2) published data generated by these investigators indicate that the ovarian hormone estradiol can antagonize the detrimental effects of 9-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 still a paucity of data regarding the effects of 9-THC on female animals, all of the planned behavioral experiments will use female rats and involve the presence or absence of ovarian hormones in 9- THC-treated subjects. In addition, the subjects in each treatment group will be sacrificed to examine potential changes in cannabinoid or estrogen receptors in relevant brain areas. Our overall hypothesis is that 17 �- estradiol can attenuate both the acute and chronic effects of 9-THC on memory in adult female rats and that a similar attenuation occurs in the hippocampus to affect its activity and role in memory. To address this hypothesis, experiments in Specific Aim 1 will determine whether ovarian hormones attenuate the acute disruptive effects of 9-THC on memory. In a similar manner, Specific Aim 2 will determine whether estradiol can attenuate the chronic effects of 9-THC on memory and facilitate the development of tolerance to those effects. Finally, Specific Aim 3 will determine whether estradiol can attenuate the disruptive effects of 9- THC on hippocampal activity. When completed, these data will demonstrate that estrogens in females can attenuate both the acute and chronic effects of �9-THC on memory, and that estrogen receptor (ER) signaling reduces cannabinoid receptor (CBR) signaling in brain areas critical for memory encoding.

描述（由适用提供）：最近的调查表明，普通人群中大麻的使用率已上升到高达7％。此外，出于医疗目的，大麻现在已在18个州和哥伦比亚特区合法化，这促成了这种非法药物可能带来与健康相关的风险最少的观念。但是，这尚未得到证实，并且确实需要了解大麻素使用和滥用的所有生物医学后果。本应用程序汇集了一个多学科研究人员的团队，以检查卵巢马，急性或慢性9-四氢大麻酚（9-THC）给药的存在是否减少了女性的记忆。长期给予9-THC特别令人感兴趣，因为这种Illici药物长期被广泛滥用，大多数潜在的治疗用途也可能需要长期给药。卵巢骑马的存在或不存在是作为辅助因子而引起的，因为：1）卵巢骑马对认知功能产生了直接和间接影响，以及2）这些研究者产生的数据，这些研究人员已发表的数据表明，卵巢荷兰雌二醇表明，卵巢雄性雌性可以拮抗9- thc对女性的障碍的障碍，并且对女性的大脑构成了cann的较大的binak，cann的含量是cann的cant虫。海马。由于这些相同的原因，并且由于关于9-THC对雌性动物的影响的数据仍然很少，因此所有计划的行为实验都将使用女性大鼠，并且涉及9-THC治疗的受试者的存在或不存在卵巢骑马。此外，每个治疗组中的受试者将被牺牲以检查潜力 相关大脑区域中大麻素或雌激素受体的变化。我们的总体假设是，17 - 雌二醇可以减弱9-THC对成年雌性大鼠记忆的急性和慢性影响，并且在海马中发生了类似的衰减，以影响其活性和在记忆中的作用。为了解决这一假设，特定目标1中的实验将确定卵巢恐怖是否减弱了9-THC对记忆的急性破坏作用。以类似的方式，特定的目标2将确定雌二醇是否可以减弱9-THC对记忆的慢性影响并支持对这些影响的耐受性的发展。最后，特定的目标3将确定雌二醇是否可以减弱9-THC对海马活性的破坏作用。完成后，这些数据将证明女性中的雌激素可以减轻9-THC对记忆的急性和慢性作用，并且雌激素受体（ER）信号传导减少了大脑受体（CBR）信号在大脑区域中对记忆编码至关重要的。