?? Adolescence?in?humans?is?a?period?of?life?when?alcohol?use?is?often?initiated.??Unfortunately,?it?is?also?a? time?when?some?individuals?develop?long?lasting?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?sex?specific?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?adolescent?to? 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?self?administration?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?pre?pubertal?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? self?administration?of?alcohol?(Aim?2).??Ultimately,?the?information?learned?in?these?studies?will?help?us? understand?if?alcohol?induced?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?alcohol?induced?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.? ? ?
