Alcohol drinking behavior and prefrontal cortex neuron loss during adolescence

University Of Illinois At Urbana-Champaign, Urbana IL

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Abstract

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