Effect of low doses of methamphetamine on rat limbic-related neurotensin systems.

Effect of low doses of methamphetamine on rat limbic-related neurotensin systems.
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低剂量的甲基苯丙胺对大鼠边缘相关神经素系统的影响。

DOI:
10.1002/syn.21829
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发表时间:
2015-08
期刊:
影响因子:
2.3
通讯作者:
Hanson, Glen R.
Hanson, Glen R.
中科院分区:
医学4区
文献类型:
--
作者:
Alburges, Mario E.;Hoonakker, Amanda J.;Cordova, Nathaniel M.;Robson, Christina M.;McFadden, Lisa M.;Martin, Amber L.;Hanson, Glen R.

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服用甲基苯丙胺(METH)会改变边缘相关(LR)神经降压素(NT)系统。因此,通过 D1 受体机制,非偶然高剂量(5-15 mg/kg)以及可能的自我给药,METH 似乎会减少 NT 释放,导致其积累,并导致边缘相关 NT 通路中 NT 样免疫反应性 (NTLI) 升高。为了进行比较,我们测试了低剂量的冰毒(更像是治疗中使用的剂量)对伏隔核(NAc 和 NAs)核心和外壳、前额皮质(PFC)、腹侧被盖区(VTA)、外侧缰核(Hb)和基底外侧杏仁核(Amyg)的 NTLI 的影响。尤其是剂量为 0.25 mg/kg(而非 1.00 mg/kg)的冰毒,降低了除前额皮质外的所有 LR 结构中的 NTLI 浓度;然而,这些效应在治疗后 5 小时观察到,但在 24 小时内观察不到,但迅速且短暂。在低剂量 METH 后 NTLI 水平降低的所有 LR 区域中,用 D1 或 D2 拮抗剂预处理可阻断该作用。因此,与滥用相关的高剂量相反,类似治疗的低剂量 METH 治疗引起的 NT 组织水平降低可能反映了 NT 释放的增加和 LR 结构中这种神经肽水平的短期消耗,表现出与基底节 NT 系统对类似低剂量 METH 的反应相当的特征。
Administration of methamphetamine (METH) alters limbic-related (LR) neurotensin (NT) systems. Thus, through a D1-receptor mechanism, noncontingent high doses (5–15 mg/kg), and likely self-administration, of METH appears to reduce NT release causing its accumulation and an elevation of NT-like immunoreactivity (NTLI) in limbic-related NT pathways. For comparison, we tested the effect of low doses of METH, that are more like those used in therapy, on NTLI in the core and shell of the nucleus accumbens (NAc and NAs), prefrontal cortex (PFC), ventral tegmental area (VTA), the lateral habenula (Hb) and basolateral amygdala (Amyg). METH at the dose of 0.25 mg/kg in particular, but not 1.00 mg/kg, decreased NTLI concentration in all of the LR structures studied, except for the prefrontal cortex; however, these effects were rapid and brief being observed at 5 h but not at 24 h after treatment. In all of the LR areas where NTLI levels were reduced after the low dose of METH, the effect was blocked by pretreatment with either a D1 or a D2 antagonist. Thus, opposite to high doses like those associated with abuse, the therapeutic-like low-dose METH treatment induced reduction in NT tissue levels likely reflected an increase in NT release and a short-term depletion of the levels of this neuropeptide in LR structures, manifesting features comparable to the response of basal ganglia NT systems to similar low doses of METH.
DOI: 10.1046/j.1471-4159.2001.00043.x
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