生物谷报道：本周刚刚出版的Nature上报道了华人学者蒲慕明教授的一篇最新研究成果：重复暴露可卡因会增强中脑多巴胺能神经元的LTP活动。研究表明，中脑腹侧被盖区（ventral tegmental area, VTA)中的多巴胺能神经元是主导性神经元。在体反复可卡因刺激后，会抑制GAGAa受体的活动，从而增强了这些多巴胺能神经元的LTP的产生，这一成果揭示了为什么反复吸食可卡因会成瘾的中枢神经系统机制，也为解决可卡因成瘾的治疗提供实验学依据。
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.
原始出处：
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
