Contributions of Progestins Independently and Interactively with Contraceptive Estrogen to Nicotine Use
孕激素独立和与避孕雌激素相互作用对尼古丁使用的贡献
基本信息
- 批准号:10592661
- 负责人:
- 金额:$ 20.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-30 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcidsAdolescenceAffectAnimalsAreaAutomobile DrivingBehavioralBrain regionCaringCellsChronicContraceptive AgentsContraceptive UsageDataElectrophysiology (science)EstradiolEstrogensEthinyl EstradiolEthinyl Estradiol/LevonorgestrelExposure toFemaleFormulationFoundationsFutureGlutamatesGoalsHormone useHormonesIntravenousLevonorgestrelMeasuresMethodsMotivationN-MethylaspartateNeurobiologyNeuronsNicotineNicotine DependenceNorethisterone AcetateNucleus AccumbensOralOral ContraceptivesOutcomeOvarianOvarian hormoneOvariectomyOvaryPathway interactionsPeriodicityPlayProceduresProgesteroneProgestinsPublic HealthPublishingRattusRelapseResearchRewardsRoleSalineSelf AdministrationSmokeSmokingSubstance Use DisorderSynaptic plasticitySystemTimeToxic effectTranslationsUnited StatesVariantWomanaddictionbasebehavioral economicsbirth controlcigarette cravingcravingcritical perioddrug rewardinsightmenneural circuitneurobehavioralnicotine rewardnicotine usenovelpatch clamppreventprotective effectreceptorreproductivereproductive developmentresiliencereward circuitrysmoking cessationxenoestrogenyoung adult
项目摘要
PROJECT SUMMARY/ABSTRACT
Long-term smoking cessation is more difficult to achieve in women than men, and more than 170,000 women
die of complications related to smoking in the United States each year. Cyclical variations in hormone levels are
differentially associated with craving and relapse to smoking in women, with increases in 17β-estradiol (E2) and
progesterone being associated with addiction vulnerability and resilience, respectively. Further, women can be
chronically maintained on synthetic hormones contained in oral contraceptives, which contain ethinyl estradiol
(EE), a synthetic, orally bio-available estrogen, and a synthetic progesterone, termed “progestins”. EE is more
potent and bioavailable than the endogenous E2, and women are prescribed EE during critical periods of
reproductive development in adolescence and young adulthood. Further, progestins such as levonorgestrel
(LEVO) or norethisterone acetate (NETA) can have either beneficial or potentially deleterious effects on women.
Despite this, there are no studies to date that have examined the impact of these synthetic hormones on nicotine
neurobehavioral outcomes in females. Nicotine produces cellular adaptations such as changes in synaptic
plasticity in brain regions associated with drug reward, especially within the nucleus accumbens core (NAcore).
Mechanistically, the E2 receptors (ERs) are located on medium spiny neurons (MSNs) within the NAcore, which
we show undergo hormone-dependent changes in synaptic plasticity (measured via the ratio of AMPA to NMDA
currents) following nicotine self-administration (SA). Further, we show that EE alone partially rescues
ovariectomy-induced decreases in nicotine consumption and demand, and LEVO decreases nicotine
consumption during SA as compared to EE+LEVO treatment in ovary-intact females. Here, we will systematically
evaluate the contributions of two different progestins, LEVO or NETA, to nicotine demand and NAcore glutamate
plasticity either independently or interactively with EE in ovary-intact females. Specifically, Aims 1a and 1b will
focus on LEVO, whereas Aims 2a and 2b will focus on NETA. We hypothesize that these two progestins will
differentially impact nicotine demand and glutamate plasticity, such that LEVO alone will reduce nicotine demand
and increase AMPA/NMDA ratios and NETA alone will increase nicotine demand and decrease AMPA/NMDA
ratios. We hypothesize that when combined with EE, the protective effects of LEVO will be occluded. Further,
we hypothesize that EE+NETA will enhance nicotine demand and further decrease AMPA/NMDA ratios, thus
exacerbating the neurobehavioral outcomes associated with nicotine use. These studies will systematically
evaluate the contributions of exogenous synthetic hormones contained in oral contraceptives to nicotine use and
will uncover unknown consequences on neural circuitry. Findings from this R21 will lay a foundation for a future
R01 application to further delve into examination of progestins contained in various other contraceptive
formulations. Together, these studies may provide insight into conditions that impact reproductive cycles, which
will allow a mechanistic understanding of nicotine use motivation in women.
项目总结/文摘
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Cassandra D Gipson-Reichardt其他文献
Cassandra D Gipson-Reichardt的其他文献
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{{ truncateString('Cassandra D Gipson-Reichardt', 18)}}的其他基金
Neurobehavioral mechanisms underlying xylazine and fentanyl co-use and withdrawal
赛拉嗪和芬太尼共同使用和戒断的神经行为机制
- 批准号:
10737712 - 财政年份:2023
- 资助金额:
$ 20.07万 - 项目类别:
Contributions of Progestins Independently and Interactively with Contraceptive Estrogen to Nicotine Use
孕激素独立和与避孕雌激素相互作用对尼古丁使用的贡献
- 批准号:
10710219 - 财政年份:2022
- 资助金额:
$ 20.07万 - 项目类别:
Neuroinflammatory and glutamatergic mechanisms of nicotine seeking
寻求尼古丁的神经炎症和谷氨酸机制
- 批准号:
10214266 - 财政年份:2020
- 资助金额:
$ 20.07万 - 项目类别:
Glutamergic Mechanisms in Opioid and Cocaine Co-Use
阿片类药物和可卡因共同使用的谷氨酸机制
- 批准号:
10669480 - 财政年份:2020
- 资助金额:
$ 20.07万 - 项目类别:
Glutamergic Mechanisms in Opioid and Cocaine Co-Use
阿片类药物和可卡因共同使用的谷氨酸机制
- 批准号:
9978489 - 财政年份:2020
- 资助金额:
$ 20.07万 - 项目类别:
Neuroinflammatory and glutamatergic mechanisms of nicotine seeking
寻求尼古丁的神经炎症和谷氨酸机制
- 批准号:
10231269 - 财政年份:2020
- 资助金额:
$ 20.07万 - 项目类别:
Neuroinflammatory and glutamatergic mechanisms of nicotine seeking
寻求尼古丁的神经炎症和谷氨酸机制
- 批准号:
10684702 - 财政年份:2020
- 资助金额:
$ 20.07万 - 项目类别:
Glutamergic Mechanisms in Opioid and Cocaine Co-Use
阿片类药物和可卡因共同使用的谷氨酸机制
- 批准号:
10264811 - 财政年份:2020
- 资助金额:
$ 20.07万 - 项目类别:
Neuroinflammatory and glutamatergic mechanisms of nicotine seeking
寻求尼古丁的神经炎症和谷氨酸机制
- 批准号:
10899797 - 财政年份:2020
- 资助金额:
$ 20.07万 - 项目类别:
Neuroinflammatory and glutamatergic mechanisms of nicotine seeking
寻求尼古丁的神经炎症和谷氨酸机制
- 批准号:
10684352 - 财政年份:2020
- 资助金额:
$ 20.07万 - 项目类别:
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