Role of estradiol in women smokers' acute HPA axis hormone response to naltrexone

雌二醇在女性吸烟者对纳曲酮的急性 HPA 轴激素反应中的作用

• 批准号: 8365275
• 负责人: Daniel Roche
• 金额: $ 2.29万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2013-01-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365275
• 关键词: Acute; Affect; Behavioral; Cigarette; Corticotropin; Estradiol; Female; Hormones; Hydrocortisone; Naltrexone; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Public Health; Role; Smoker; Smoking Behavior; Woman; craving; male; men; response; sex; smoking cessation

DESCRIPTION (provided by applicant): endogenousopioidsystemisinvolvedinacuteresponsetonicotineandthedevelopmentand maintenanceofnicotinedependence.Accordingly,onedrugbeinginvestigatedforsmokingcessation treatmentisnaltrexone,aopioidreceptorantagonist.However,recentclinicaltrialsexaminingtheefficacyof adjunctivetreatmentwithnaltrexoneinsmokingcessationhaveyieldedmixedresultsand,therefore,further researchisneeded.Ofpotentialrelevancetotheseclinicaloutcomes,boththeendogenousopioidsystemand nicotinehaveactiononthehypothalamicpituitaryadrenal(HPA)axis,asystemthatisprimarilyassociated withresponsetostress.SmokershaveanacutelyunderresponsiveHPAaxistostressorsor pharmacologicalactivationcomparedtononsmokers.Importantly,thisHPAaxisdysfunctionmayplayarole inmaintenanceofaddictionandsusceptibilitytorelapse.NaltrexoneacutelyactivatestheHPAaxisandithas beenpreviouslyhypothesizedthatthisincreaseinHPAaxisactivitymayunderlienaltrexone'sefficacyfor treatmentofalcoholismandpossiblysmoking.However,therelationshipbetweennaltrexone'sactiononthe HPAaxisanditsreductionofsmokingbehaviorhasnotbeeninvestigated.Finally,theremaybeimportant,yet unexploredsexdifferencesinsmokers'responsetonaltrexone.Womensmokershaveshownmoreacute sensitivitytonaltrexonethanmenintermsofsubjective,behavioral,andHPAaxishormonemeasures,aswell asbetterquitratesinsmokingcessationtrialsusingnaltrexone.Thesereportedsexdifferencesmaybe relatedtodifferencesinlevelsofestradiol,thepredominantestrogeninhumans,betweenmenandwomen.In women,fluctuationsinestradiollevelsacrossthemenstrualcyclemayaffecttheamountofavailableopioid receptorsand,therefore,mayaffecttheefficacyofnaltrexone.Thestudiesinthisapplicationaredesignedto testtheeffectsofnaltrexoneontheHPAaxisandsmokingbehaviorinmaleandfemalesmokers,andto examinehowestradiollevelaffectstheseresponsestonaltrexoneinfemalesmokers.Inordertoexaminethe effectofestradiolonresponsetonaltrexone,womenwillbetestedattwodifferentstagesofthemenstrual cycle:theearlyfollicularphase(thelowestlevelofestradioloccurringduringthemenstrualcycle)andthelate follicularphase(thehighestoccurringlevelofestradiol).Theresultsofthisstudywouldpotentiallyprovide evidenceforestradiollevelasamechanismunderlyingsexdifferencesinresponsetonaltrexoneandmay havetranslationalclinicalimplicationsfortheuseofnaltrexoneinsmokingcessation.

说明(申请人提供)：endogenousopioidsystemisinvolvedinacuteresponsetonicotineandthedevelopmentand对尼古丁依赖的维持。相应地，一项正在研究的戒烟治疗试验表明，阿片受体拮抗剂--曲曲酮。然而，最近的临床试验检验了adjunctivetreatmentwithnaltrexoneinsmokingcessationhaveyieldedmixedresultsand，的有效性，因此，进一步researchisneeded.Ofpotentialrelevancetotheseclinicaloutcomes，内源性药物系统和nicotinehaveactiononthehypothalamicpituitaryadrenal(HPA)axis，系统的特殊关联withresponsetostress.SmokershaveanacutelyunderresponsiveHPAaxistostressorsor pharmacologicalactivationcomparedtononsmokers.Importantly，这一功能障碍可能与inmaintenanceofaddictionandsusceptibilitytorelapse.NaltrexoneacutelyactivatestheHPAaxisandithas beenpreviouslyhypothesizedthatthisincreaseinHPAaxisactivitymayunderlienaltrexone‘sefficacyfor treatmentofalcoholismandpossiblysmoking.However，在HPAaxisanditsreductionofsmokingbehaviorhasnotbeeninvestigated.Finally，的行为和unexploredsexdifferencesinsmokers’responsetonaltrexone.Womensmokershaveshownmoreacute sensitivitytonaltrexonethanmenintermsofsubjective，水平上的asbetterquitratesinsmokingcessationtrialsusingnaltrexone.Thesereportedsexdifferencesmaybe反应之间存在一定的关系，而fluctuationsinestradiollevelsacrossthemenstrualcyclemayaffecttheamountofavailableopioid在辐射水平上的差异，主要是在人类和女性之间。因此，在女性中，mayaffecttheefficacyofnaltrexone.Thestudiesinthisapplicationaredesignedto testtheeffectsofnaltrexoneontheHPAaxisandsmokingbehaviorinmaleandfemalesmokers，接受和examinehowestradiollevelaffectstheseresponsestonaltrexoneinfemalesmokers.Inordertoexaminethe对womenwillbetestedattwodifferentstagesofthemenstrual cycle:theearlyfollicularphase(thelowestlevelofestradioloccurringduringthemenstrualcycle)andthelate follicularphase(thehighestoccurringlevelofestradiol).Theresultsofthisstudywouldpotentiallyprovide evidenceforestradiollevelasamechanismunderlyingsexdifferencesinresponsetonaltrexoneandmay havetranslationalclinicalimplicationsfortheuseofnaltrexoneinsmokingcessation.的辐射设置的影响可能与HPA的作用有关。