Drugs of abuse and stress impair LTP at inhibitory synapses in the ventral tegmental area.
Drugs of abuse and stress impair LTP at inhibitory synapses in the ventral tegmental area.
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DOI：
10.1111/j.1460-9568.2010.07256.x
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发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Kauer JA
中科院分区：
文献类型：
--
作者：
Niehaus JL;Murali M;Kauer JA
腹侧被盖区（VTA）的突触可塑性受药物滥用和压力的调节，并被假设为有助于成瘾的特定方面。腹侧被盖区多巴胺神经元上的兴奋性和抑制性突触都能够经历突触强度的长期变化。虽然腹侧被盖区兴奋性突触的增强或减弱已被广泛研究，但抑制性突触可塑性在大脑奖赏回路中的作用还不太确定。在这里，我们研究了药物滥用，以及急性应激，对GABA能突触到腹侧被盖区多巴胺神经元（LTPGABA）的长时程增强的影响。吗啡（10 mg/kg i. p.）在药物暴露后2小时和24小时降低了中脑切片中抑制性突触表达LTPGABA的能力，但在5天后没有。钴（15 mg/kg i.p.）暴露后24小时LTPGABA受损，但2小时未受损。尼古丁（0.5 mg/kg i. p.）LTPGABA在暴露后2小时受损，但在24小时后未受损。此外，LTPGABA完全阻断24小时后，短暂暴露于应激刺激，强迫游泳任务。我们的数据表明，药物滥用和压力触发了一个共同的修改抑制可塑性，协同其集体效应在兴奋性突触。总之，成瘾物质或压力的净效应预计会增加腹侧被盖区多巴胺神经元的兴奋性，可能有助于成瘾的早期阶段。
Synaptic plasticity in the ventral tegmental area (VTA) is modulated by drugs of abuse and stress and is hypothesized to contribute to specific aspects of addiction. Both excitatory and inhibitory synapses on dopamine neurons in the VTA are capable of undergoing long-term changes in synaptic strength. While the strengthening or weakening of excitatory synapses in the VTA has been widely examined, the role of inhibitory synaptic plasticity in brain reward circuitry is less established. Here, we investigated the effects of drugs of abuse, as well as acute stress, on long-term potentiation of GABAergic synapses onto VTA dopamine neurons (LTPGABA). Morphine (10 mg/kg i.p.) reduced the ability of inhibitory synapses in midbrain slices to express LTPGABA both at 2 and 24 hours after drug exposure but not after 5 days. Cocaine (15 mg/kg i.p.) impaired LTPGABA 24 hours after exposure, but not at 2 hours. Nicotine (0.5 mg/kg i.p.) impaired LTPGABA 2 hours after exposure, but not after 24 hours. Furthermore, LTPGABA was completely blocked 24 hours following brief exposure to a stressful stimulus, a forced swim task. Our data suggest that drugs of abuse and stress trigger a common modification to inhibitory plasticity, synergizing with their collective effect at excitatory synapses. Together, the net effect of addictive substances or stress is expected to increase excitability of VTA dopamine neurons, potentially contributing to the early stages of addiction.
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影响因子：
5.3
作者：
Borgland, SL;Malenka, RC;Bonci, A
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.0401553101
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通讯作者：
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