Cocaine-induced plasticity in the nucleus accumbens is cell specific and develops without prolonged withdrawal.
Cocaine-induced plasticity in the nucleus accumbens is cell specific and develops without prolonged withdrawal.
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DOI：
10.1523/jneurosci.5375-10.2011
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发表时间：
2011-02-02
期刊：
影响因子：
--
通讯作者：
Alvarez VA
中科院分区：
文献类型：
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作者：
Dobi A;Seabold GK;Christensen CH;Bock R;Alvarez VA
辅酶A在丘脑核（NAc）中的多巴胺能突触处诱导可塑性。研究表明，在最后一次接触可卡因几周后，某些变化才出现，这表明戒断在这种可塑性的发展中起着重要作用。在本研究中，通过比较两种不同的非偶然可卡因治疗诱导的多巴胺能传递的变化来评估延长戒断的要求：短期治疗后延长戒断，以及较长时间的治疗而不延长戒断。在两种治疗下第一次注射可卡因后的同一时间，从小鼠NAc中的中型多刺神经元（MSN）进行记录。谷氨酸介导的微型兴奋性突触后电流（mEPSC）的频率类似的增加，观察到在D1表达的MSN可卡因治疗后，证明长期戒断是不需要的。此外，在长期可卡因治疗后没有戒断的情况下，观察到较大的AMPAR与NMDAR比值、较高的脊柱密度和增大的脊柱头部。这些突触适应中表达的D1-含MSN的NAc核心没有进一步增强延长戒断。总之，几次重复的可卡因注射足以触发D1表达MSN的突触适应，尽管它们需要时间来发展，但不需要长时间的可卡因戒断。
Cocaine induces plasticity at glutamatergic synapses in the nucleus accumbens (NAc). Withdrawal was suggested to play an important role in the development of this plasticity by studies showing that some changes only appear several weeks after the final cocaine exposure. In this study, the requirement for prolonged withdrawal was evaluated by comparing the changes in glutamatergic transmission induced by two different non-contingent cocaine treatments: a short treatment followed by prolonged withdrawal, and a longer treatment without prolonged withdrawal. Recordings were performed from mouse medium spiny neurons (MSNs) in the NAc at the same time after the first cocaine injection under both treatments. A similar increase in the frequency of glutamate-mediated miniature excitatory postsynaptic currents (mEPSCs) was observed in D1-expressing MSNs after both cocaine treatments, demonstrating that prolonged withdrawal was not required. Furthermore, larger AMPAR to NMDAR ratios, higher spine density and enlarged spine heads were observed in the absence of withdrawal following a long cocaine treatment. These synaptic adaptations expressed in D1-containing MSNs of the NAc core were not further enhanced by protracted withdrawal. In conclusion, a few repeated cocaine injections are enough to trigger adaptations at glutamatergic synapses in D1-expressing MSNs, which although they take time to develop, do not require prolonged cocaine withdrawal.