Cocaine treatment followed by prolonged withdrawal disrupts mPFC inputs to VTA
作者单位：Medical University of South CarolinaCharleston29425USA
会议名称：《中国神经科学学会第四次会员代表大会暨第八届全国学术会议》
会议日期：2009年
学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
关 键 词：cocaine prolonged withdrawal extracellular single-unit recording mPFC inputs to VTA dopamine neurons
摘 要：正Objective The medial prefrontal cortex（mPFC） inputs to the ventral tegmental area（VTA） are important to the function of the dopamine（DA） system,influencing its role in reward and drug *** Using in vivo extracellular single-unit recording,we investigated the effects of repeated cocaine treatment followed by protracted withdrawal（2- 4 weeks） on the responsiveness of VTA DA neurons to electrical stimulation of *** We found that VTA DA neurons in cocaine- and saline-treated animals exhibited a similar firing rate before,during and after the ventral mPFC electric ***,2-4 week abstinence decreased bursting during the baseline（%of spikes firing in burst （%SIB）:abstinent rats vs saline rats:29.47±5.34 vs 40.16±4.67,P0.05）.Additionally,the change in%SIB during ventral mPFC stimulation showed significant differences between cocaine abstinent rats and saline-pretreated rats（abstinent rats vs saline rats:7.5±0.7 vs -7.7±0.9,P0.01）.Furthermore,the proportion of VTA dopamine neurons exhibiting short latency mPFC-evoked excitations（ 25 ms） was higher in saline-treated animals than cocaine abstinent rats（47.1%vs15.0%）.In contrast to saline-treated animals,cocaine treated rats exhibited longer long-onset latency activation on average（abstinent rats vs saline rats:315±48 ms vs 132±11ms,P0.05）.Finally,this decrease in frequency of short-latency evoked excitations was replicated in animals that had undergone 10 days of cocaine self-administration（2/22 DA neurons） or 10 days cocaine self-administration followed by two-week abstinence（1/18 DA neurons）.Conclusion The results of this study provide the evidence that repeated cocaine treatment,as well as cocaine treatment followed by prolonged withdrawal,disrupts mPFC inputs to *** data suggest that extensive cocaine exposure may influence cognitive control over reward seeking, potentially providing a mechanism for increased drug-seeking during withdrawal and relapse states.