单剂量可卡因可提高青春期大鼠海马中 SV2A 的密度。

IF 3.8 4区 医学 Q1 Medicine Acta Neuropsychiatrica Pub Date : 2024-04-01 Epub Date: 2023-02-27 DOI:10.1017/neu.2023.14
Rachele Rossi, Simone Larsen Bærentzen, Majken B Thomsen, Caroline C Real, Gregers Wegener, Rodrigo Grassi-Oliveira, Albert Gjedde, Anne M Landau
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引用次数: 0

摘要

目的:可卡因是一种高度成瘾的精神兴奋剂,会影响神经元结构和功能适应性的突触活动。突触前囊泡的跨膜突触囊泡糖蛋白 2A(SV2A)通常用于测量突触密度,是检测突触变化的一种新方法。我们不知道单剂量的可卡因是否足以影响突触前 SV2A 密度,尤其是在突触高度成熟的青春期。在此,我们探讨了目标脑区突触前 SV2A 密度的潜在变化,这些变化与可卡因诱导的多巴胺能神经递质增强有关,特别是测试了这些影响是否会在多巴胺水平恢复到基线后持续:我们给青春期早期的大鼠注射可卡因(20 毫克/千克,静脉注射)或生理盐水,测试它们的活动水平,并在注射后 1 小时和 7 天取出大脑。为了评估可卡因对大鼠的直接和持久影响,我们在大鼠内侧前额叶皮层、纹状体、伏隔核、杏仁核以及海马的背侧和腹侧区域用 SV2A 的特异性示踪剂 [3H]UCB-J 进行了自显影。我们还测量了纹状体与[3H]GBR-12935的结合情况,以检验可卡因在两个研究时间段对多巴胺转运体的占据情况:结果:我们发现,与注射生理盐水的大鼠相比,注射可卡因 7 天后海马背侧和腹侧切片中的 [3H]UCB-J 结合率明显增加,但注射 1 小时后则无差异。结论:可卡因会引起大鼠海马的持久变化:结论:青春期大鼠单次接触可卡因后,海马突触 SV2A 密度会发生持久变化。
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A single dose of cocaine raises SV2A density in hippocampus of adolescent rats.

Objective: Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane synaptic vesicle glycoprotein 2A (SV2A) of pre-synaptic vesicles is commonly used to measure synaptic density, as a novel approach to the detection of synaptic changes. We do not know if a single dose of cocaine suffices to affect pre-synaptic SV2A density, especially during adolescence when synapses undergo intense maturation. Here, we explored potential changes of pre-synaptic SV2A density in target brain areas associated with the cocaine-induced boost of dopaminergic neurotransmission, specifically testing if the effects would last after the return of dopamine levels to baseline.

Methods: We administered cocaine (20 mg/kg i.p.) or saline to rats in early adolescence, tested their activity levels and removed the brains 1 hour and 7 days after injection. To evaluate immediate and lasting effects, we did autoradiography with [3H]UCB-J, a specific tracer for SV2A, in medial prefrontal cortex, striatum, nucleus accumbens, amygdala, and dorsal and ventral areas of hippocampus. We also measured the striatal binding of [3H]GBR-12935 to test cocaine's occupancy of the dopamine transporter at both times of study.

Results: We found a significant increase of [3H]UCB-J binding in the dorsal and ventral sections of hippocampus 7 days after the cocaine administration compared to saline-injected rats, but no differences 1 hour after the injection. The [3H]GBR-12935 binding remained unchanged at both times.

Conclusion: Cocaine provoked lasting changes of hippocampal synaptic SV2A density after a single exposure during adolescence.

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来源期刊
Acta Neuropsychiatrica
Acta Neuropsychiatrica 医学-精神病学
CiteScore
8.50
自引率
5.30%
发文量
30
审稿时长
6-12 weeks
期刊介绍: Acta Neuropsychiatrica is an international journal focussing on translational neuropsychiatry. It publishes high-quality original research papers and reviews. The Journal''s scope specifically highlights the pathway from discovery to clinical applications, healthcare and global health that can be viewed broadly as the spectrum of work that marks the pathway from discovery to global health.
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