Acute and chronic cocaine-induced potentiation of synaptic strength in the ventral tegmental area: Electrophysiological and behavioral correlates in individual rats
Acute and chronic cocaine-induced potentiation of synaptic strength in the ventral tegmental area: Electrophysiological and behavioral correlates in individual rats
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DOI：
10.1523/jneurosci.1312-04.2004
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发表时间：
2004-08-25
影响因子：
5.3
通讯作者：
Bonci, A
中科院分区：
文献类型：
--
作者：
Borgland, SL;Malenka, RC;Bonci, A
精神兴奋剂敏感化过程的启动依赖于中脑边缘系统，该系统从腹侧被盖区（VTA）投射到丘脑核。虽然这种启动主要依赖于腹侧被盖区神经元的突触能活动，但腹侧被盖区兴奋性突触在这一过程中的确切作用尚不清楚。在这里，我们检查了重复体内注射可卡因对先前报道的由单次体内暴露于可卡因引起的VTA兴奋性突触处强度增加的幅度和持续时间的影响（Ungless等人，2001;萨尔等人，2003年）。我们还比较了可卡因引起的突触修饰与其对自发活动的影响。令人惊讶的是，重复的可卡因暴露增强AMPA受体介导的NMDA受体介导的EPSC的比例，以类似的程度和持续时间作为一个单一的体内可卡因暴露。在幼稚动物中，可卡因诱导的运动活动的幅度与伴随的突触增强的幅度相关。这种相关性在重复可卡因给药的第七天以及在停止重复可卡因给药后10天给予激发注射时丢失。这些结果表明，可卡因诱导的腹侧被盖兴奋性突触的突触可塑性是短暂的，其持续时间取决于最后一次接触可卡因的时间。此外，慢性可卡因暴露破坏了正常的，可能是适应性的腹侧被盖区突触增强和行为之间的关系。
The initiation of the psychostimulant sensitization process depends on the mesolimbic system, which projects from the ventral tegmental area (VTA) to the nucleus accumbens. Although such initiation is primarily dependent on glutamatergic activity in VTA neurons, the exact role VTA excitatory synapses play in this process is poorly understood. Here, we examine the effects of repeated in vivo injections of cocaine on the magnitude and duration of the increase in strength at VTA excitatory synapses reported previously to be elicited by a single in vivo exposure to cocaine (Ungless et al., 2001; Saal et al., 2003). We also compare the synaptic modifications induced by cocaine with its effects on locomotor activity. Surprisingly, repeated cocaine exposure potentiated the ratio of AMPA receptor-mediated to NMDA receptor-mediated EPSCs to a similar extent and duration as a single in vivo cocaine exposure. In naive animals, the magnitude of the cocaine-induced locomotor activity after a single injection of cocaine correlated with the magnitude of the accompanying synaptic enhancement. This correlation was lost on the seventh day of repeated cocaine administration, as well as when a challenge injection was given 10 d after the cessation of repeated cocaine administration. These results suggest that the cocaine-induced synaptic plasticity at VTA excitatory synapses is transient, and its duration depends on the last exposure to cocaine. Furthermore, chronic cocaine exposure disrupts the normal, presumably adaptive relationship between synaptic enhancement in the VTA and behavior.