Alcohol drinking behavior and prefrontal cortex neuron loss during adolescence

青春期饮酒行为与前额皮质神经元丢失

• 批准号: 7503401
• 负责人: Joshua M Gulley
• 金额: $ 17.19万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7503401
• 关键词: Adolescence; Adolescent; Adult; Age; Alcohol consumption; Alcohol dependence; Alcoholism; Alcohols; Animal Model; Animals; Area; Behavior; Brain; Cell Death; Cells; Cellular Structures; Development; Electrophysiology (science); Estrogens; Ethanol; Excision; Exposure to; Female; Foundations; Funding Mechanisms; Gonadal Hormones; Gonadal Steroid Hormones; Grant; Hormonal; Hormones; Human; Individual; Laboratories; Learning; Life; Literature; Medial; Mediating; Metabolic; Methods; Nervous system structure; Neurons; Neurotransmitters; Numbers; Pattern; Pharmaceutical Preparations; Prefrontal Cortex; Prevalence; Prevention; Progesterone; Rate; Rattus; Reporting; Research; Risk; Saline; Self Administration; Sex Characteristics; Synapses; System; Techniques; Testing; Testosterone; Time; Training; Work; abstracting; alcohol effect; alcohol exposure; alcohol response; alcoholism/alcohol abuse; base; drinking; drinking behavior; in vivo; insight; male; neuron loss; research study; sex

6.¿¿PROJECT¿SUMMARY/ABSTRACT¿¿ Adolescence¿in¿humans¿is¿a¿period¿of¿life¿when¿alcohol¿use¿is¿often¿initiated.¿¿Unfortunately,¿it¿is¿also¿a¿ time¿when¿some¿individuals¿develop¿longlasting¿patterns¿of¿alcohol¿abuse¿and¿alcoholism.¿¿Human¿and¿ animal¿studies¿have¿revealed¿that¿during¿adolescence,¿brain¿areas¿such¿as¿the¿prefrontal¿cortex¿(PFC)¿are¿ undergoing¿significant,¿yet¿normal,¿changes¿in¿synaptic¿connectivity.¿¿These¿changes¿in¿synaptic¿organization¿ have¿important¿implications¿in¿the¿adolescent¿and¿adult¿PFC.¿¿For¿example,¿in¿a¿recent¿report¿(Markam¿et¿al.,¿ 2007),¿we¿demonstrated¿region¿and¿sexspecific¿decreases¿in¿the¿number¿of¿neurons¿in¿the¿medial¿PFC¿(mPFC)¿ of¿adolescent¿compared¿to¿adult¿rats.¿¿It¿is¿possible¿that¿alcohol¿alters¿these¿normal¿patterns¿of¿adolescentto adult¿changes¿in¿mPFC¿and¿thereby¿produces¿a¿particularly¿susceptible¿nervous¿system.¿¿Furthermore,¿ pubertal¿hormones¿may¿interact¿with¿alcohol's¿effects¿in¿the¿mPFC,¿and¿this¿might¿contribute¿to¿sex¿ differences¿in¿drinking¿behavior.¿¿¿ In¿the¿research¿proposed¿here,¿we¿will¿use¿animal¿models¿to¿explore¿the¿effects¿of¿alcohol¿exposure¿during¿ adolescence¿on¿the¿mPFC¿and¿on¿the¿operant¿selfadministration¿of¿alcohol¿in¿adulthood.¿This¿will¿be¿ accomplished¿by:¿(1)¿examining¿whether¿alcohol¿exposure¿during¿adolescence¿alters¿decreases¿in¿neuron¿ number¿in¿the¿rat¿mPFC¿and¿if¿gonadal¿hormones¿contribute¿to¿alcohol's¿effects;¿and¿(2)¿investigate¿whether¿ alcohol¿exposure¿during¿adolescence¿alters¿alcohol¿drinking¿behavior¿in¿adulthood¿and¿if¿there¿is¿an¿influence¿ of¿sex¿and¿hormonal¿status.¿¿Rats¿will¿be¿divided¿into¿eight¿different¿groups¿(n¿=¿10/group)¿based¿on¿sex¿(male¿ or¿female),¿hormone¿status¿(intact¿or¿prepubertal¿gonadectomy),¿and¿adolescent¿exposure¿to¿alcohol¿(saline¿or¿ 3.0¿g/kg¿ethanol).¿¿As¿adults¿(PND¿90),¿rats¿will¿be¿either¿euthanized¿for¿brain¿removal¿and¿subsequent¿ stereological¿analysis¿of¿the¿number¿of¿neurons¿in¿the¿mPFC¿(Aim¿1)¿or¿they¿will¿begin¿training¿for¿operant¿ selfadministration¿of¿alcohol¿(Aim¿2).¿¿Ultimately,¿the¿information¿learned¿in¿these¿studies¿will¿help¿us¿ understand¿if¿alcoholinduced¿brain¿changes¿are¿a¿contributing¿factor¿to¿the¿high¿rates¿of¿alcoholism¿in¿ individuals¿who¿begin¿drinking¿at¿an¿early¿age.¿¿¿ 7.¿¿PROJECT¿NARRATIVE¿ ¿ The¿results¿of¿these¿experiments¿in¿animal¿models,¿which¿assess¿the¿effects¿of¿adolescent¿alcohol¿exposure¿on¿ medial¿prefrontal¿cortex¿neuron¿number,¿will¿also¿help¿clarify¿how¿exposure¿to¿alcohol¿early¿in¿life¿influences¿ alcohol¿drinking¿behavior¿in¿adulthood.¿¿Ultimately,¿the¿information¿learned¿in¿these¿studies¿will¿help¿us¿ understand¿if¿alcoholinduced¿brain¿changes¿are¿a¿contributing¿factor¿to¿the¿high¿rates¿of¿alcoholism¿in¿ individuals¿who¿begin¿drinking¿at¿an¿early¿age.¿¿Furthermore,¿the¿insight¿gained¿from¿these¿studies¿can¿be¿ used¿to¿develop¿more¿personalized,¿and¿thereby¿more¿effective,¿prevention¿and¿treatment¿strategies.¿ ¿ ¿

6.项目摘要/摘要 Adolescence¿in¿humans¿is¿a¿period¿of¿life¿when¿alcohol¿use¿is¿often¿initiated.¿¿Unfortunately，也是 Time¿when¿some¿individuals¿develop¿longlasting¿patterns¿of¿alcohol¿abuse¿and¿alcoholism.¿¿Human¿and¿ Animal¿studies¿have¿revealed¿that¿during¿adolescence，¿brain¿areas¿such¿as¿the¿prefrontal¿cortex¿(PFC)¿are¿ 正在经历重大而又正常的¿changes¿in¿synaptic¿connectivity.¿¿These¿changes¿in¿synaptic¿organization¿ Have¿important¿implications¿in¿the¿adolescent¿and¿adult¿PFC.¿¿For¿example，在最近的报告中(Markam等人， 2007)，¿we¿demonstrated¿region¿and¿sexspecific¿decreases¿in¿the¿number¿of¿neurons¿in¿the¿medial¿PFC¿(mPFC)¿ Of¿adolescent¿compared¿to¿adult¿rats.¿¿It¿is¿possible¿that¿alcohol¿alters¿these¿normal¿patterns¿of¿adolescentto Adult¿changes¿in¿mPFC¿and¿thereby¿produces¿a¿particularly¿susceptible¿nervous¿system.¿¿Furthermore，？ Pubertal¿hormones¿may¿interact¿with¿alcohol‘s¿effects¿in¿the¿mPFC，和这可能有助于性行为 饮酒行为的差异。 在这里提出的研究中，¿we¿will¿use¿animal¿models¿to¿explore¿the¿effects¿of¿alcohol¿exposure¿during¿ Adolescence¿on¿the¿mPFC¿and¿on¿the¿operant¿selfadministration¿of¿alcohol¿in¿adulthood.¿This¿will¿be¿ Accomplished¿by：¿(1)¿examining¿whether¿alcohol¿exposure¿during¿adolescence¿alters¿decreases¿in¿neuron¿ Number¿in¿the¿rat¿mPFC¿and¿if¿gonadal¿hormones¿contribute¿to¿alcohol‘s¿effects；¿and¿(2)¿investigate¿whether¿ Alcohol¿exposure¿during¿adolescence¿alters¿alcohol¿drinking¿behavior¿in¿adulthood¿and¿if¿there¿is¿an¿influence¿ Of¿sex¿and¿hormonal¿status.¿¿Rats¿will¿be¿divided¿into¿eight¿different¿groups¿(n¿=¿10/group)¿based¿on¿sex¿(male¿ 或女性)，¿hormone¿status¿(intact¿or¿prepubertal¿gonadectomy)，¿and¿adolescent¿exposure¿to¿alcohol¿(saline¿or¿ 3.0g/kg乙醇)。成人(PND？90)，¿rats¿will¿be¿either¿euthanized¿for¿brain¿removal¿and¿subsequent¿ Stereological¿analysis¿of¿the¿number¿of¿neurons¿in¿the¿mPFC¿(Aim¿1)¿or¿they¿will¿begin¿training¿for¿operant¿ Selfadministration¿of¿alcohol¿(Aim¿2).¿¿Ultimately，¿the¿information¿learned¿in¿these¿studies¿will¿help¿us¿ Understand¿if¿alcoholinduced¿brain¿changes¿are¿a¿contributing¿factor¿to¿the¿high¿rates¿of¿alcoholism¿in¿ Individuals¿who¿begin¿drinking¿at¿an¿early¿age.¿¿¿7.项目叙事 ？ The¿results¿of¿these¿experiments¿in¿animal¿models，¿which¿assess¿the¿effects¿of¿adolescent¿alcohol¿exposure¿on¿ 内侧前额叶皮质神经元数量，¿will¿also¿help¿clarify¿how¿exposure¿to¿alcohol¿early¿in¿life¿influences¿ Alcohol¿drinking¿behavior¿in¿adulthood.¿¿Ultimately，¿the¿information¿learned¿in¿these¿studies¿will¿help¿us¿ Understand¿if¿alcoholinduced¿brain¿changes¿are¿a¿contributing¿factor¿to¿the¿high¿rates¿of¿alcoholism¿in¿ Individuals¿who¿begin¿drinking¿at¿an¿early¿age.¿¿Furthermore，¿the¿insight¿gained¿from¿these¿studies¿can¿be¿ 用于制定更个性化、更有效的预防和治疗策略。 ？ ？

项目成果

Sex differences in the effects of ethanol pre-exposure during adolescence on ethanol-induced conditioned taste aversion in adult rats.

• DOI: 10.1016/j.bbr.2011.07.003
• 发表时间: 2011-11-20
• 期刊: BEHAVIOURAL BRAIN RESEARCH
• 影响因子: 2.7
• 作者: Sherrill, Luke K.;Berthold, Claire;Koss, Wendy A.;Juraska, Janice M.;Gulley, Joshua M.
• 通讯作者: Gulley, Joshua M.

The effects of abused drugs on adolescent development of corticolimbic circuitry and behavior.

• DOI: 10.1016/j.neuroscience.2013.05.026
• 发表时间: 2013-09-26
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Gulley JM;Juraska JM
• 通讯作者: Juraska JM

Disruptive effect of amphetamines on Pavlovian to instrumental transfer.

• DOI: 10.1016/j.bbr.2010.08.040
• 发表时间: 2011-01-01
• 期刊: BEHAVIOURAL BRAIN RESEARCH
• 影响因子: 2.7
• 作者: Hall, Darien A.;Gulley, Joshua M.
• 通讯作者: Gulley, Joshua M.