生物谷報(bào)道：本周剛剛出版的Nature上報(bào)道了華人學(xué)者蒲慕明教授的一篇最新研究成果：重復(fù)暴露可卡因會(huì)增強(qiáng)中腦多巴胺能神經(jīng)元的LTP活動(dòng),。研究表明,，中腦腹側(cè)被蓋區(qū)（ventral tegmental area, VTA)中的多巴胺能神經(jīng)元是主導(dǎo)性神經(jīng)元。在體反復(fù)可卡因刺激后，會(huì)抑制GAGAa受體的活動(dòng)，從而增強(qiáng)了這些多巴胺能神經(jīng)元的LTP的產(chǎn)生,，這一成果揭示了為什么反復(fù)吸食可卡因會(huì)成癮的中樞神經(jīng)系統(tǒng)機(jī)制，也為解決可卡因成癮的治療提供實(shí)驗(yàn)學(xué)依據(jù),。
Drugs of abuse are known to cause persistent modification of neural circuits, leading to addictive behaviours. Changes in synaptic plasticity in dopamine neurons of the ventral tegmental area (VTA) may contribute to circuit modification induced by many drugs of abuse, including cocaine. Here we report that, following repeated exposure to cocaine in vivo, excitatory synapses to rat VTA dopamine neurons become highly susceptible to the induction of long-term potentiation (LTP) by correlated pre- and postsynaptic activity. This facilitated LTP induction is caused by cocaine-induced reduction of GABAA (-aminobutyric acid) receptor-mediated inhibition of these dopamine neurons. In midbrain slices from rats treated with saline or a single dose of cocaine, LTP could not be induced in VTA dopamine neurons unless GABA-mediated inhibition was reduced by bicuculline or picrotoxin. However, LTP became readily inducible in slices from rats treated repeatedly with cocaine; this LTP induction was prevented by enhancing GABA-mediated inhibition using diazepam. Furthermore, repeated cocaine exposure reduced the amplitude of GABA-mediated synaptic currents and increased the probability of spike initiation in VTA dopamine neurons. This cocaine-induced enhancement of synaptic plasticity in the VTA may be important for the formation of drug-associated memory.
原始出處：
Qing-song Liu, Lu Pu and Mu-ming Poo. Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons. Nature 437, 1027-1031
