Insulin restores the neurochemical effects of nicotine in the mesolimbic pathway of diabetic rats.
Insulin restores the neurochemical effects of nicotine in the mesolimbic pathway of diabetic rats.
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DOI：
10.1111/jnc.15104
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发表时间：
2021-01
影响因子：
4.7
通讯作者：
O'Dell LE
中科院分区：
文献类型：
--
作者：
Cruz B;Carcoba LM;Flores RJ;Espinoza EJ;Nazarian A;O'Dell LE
本研究探讨了胰岛素是否调节尼古丁在糖尿病大鼠中脑边缘通路中的神经化学作用。大鼠接受载体或链脲佐菌素（STZ）诱导低胰岛素血症。一部分STZ处理的大鼠被植入胰岛素颗粒，迅速使血糖水平正常化。两周后，将透析探针植入同侧中脑腹侧被盖区（VTA）和中脑外侧核（NAc）。第二天，在基线期间采集透析液样本，然后在全身给予尼古丁后采集。还在VTA内给予γ-氨基丁酸（GABA）A受体拮抗剂荷包牡丹碱后收集样品。多巴胺，乙酰胆碱（ACh），GABA和谷氨酸水平进行了评估，使用液相色谱/质谱法（LC/MS）。结果显示，溶剂处理的大鼠表现出尼古丁诱导的NAc多巴胺水平增加。相比之下，STZ治疗的大鼠没有显示任何变化，在NAc多巴胺尼古丁管理，效果可能与伴随的GABA的增加和谷氨酸水平的下降，在NAc和VTA。VTA内荷包牡丹碱给药增加了溶剂处理大鼠的NAc多巴胺，这在STZ处理大鼠中是不存在的。溶剂处理的大鼠表现出尼古丁诱导的乙酰胆碱水平的增加，在NAc（但不是VTA），STZ处理的大鼠的NAc的效果较低。补充胰岛素使STZ处理大鼠NAc和VTA中尼古丁的神经化学作用正常化，表明胰岛素调节STZ处理大鼠中脑边缘通路中尼古丁的神经化学作用。本研究的目的是检查胰岛素是否调节尼古丁在糖尿病大鼠中边缘通路中的神经化学作用。结果显示，缺乏胰岛素抑制尼古丁诱导的多巴胺传递增加，这种作用是通过中脑边缘通路细胞体区域多巴胺释放的氨基酸控制来调节的。重要的是，尼古丁的神经化学作用在接受胰岛素补充的低胰岛素血症大鼠中恢复到对照水平。这项工作表明，胰岛素是一种关键的激素，调节尼古丁在中脑边缘通路的神经化学作用。
This study examined whether insulin modulates the neurochemical effects of nicotine in the mesolimbic pathway of diabetic rats. Rats received vehicle or streptozotocin (STZ) to induce hypoinsulinemia. A subset of STZ-treated rats was implanted with insulin pellets that rapidly normalized glucose levels. Two-weeks later, dialysis probes were implanted into the nucleus accumbens (NAc) and ipsilateral ventral tegmental area (VTA). The next day, dialysate samples were collected during baseline and then following systemic administration of nicotine. Samples were also collected following intra-VTA administration of the gamma-aminobutyric acid (GABA)A receptor antagonist, bicuculline. Dopamine, acetylcholine (ACh), GABA, and glutamate levels were assessed using liquid chromatography/mass spectrometry (LC/MS). The results revealed that vehicle-treated rats displayed a nicotine-induced increase in NAc dopamine levels. In contrast, STZ-treated rats did not display any changes in NAc dopamine following nicotine administration, an effect that was likely related to a concomitant increase in GABA and decrease in glutamate levels in both the NAc and VTA. Intra-VTA administration of bicuculline increased NAc dopamine in vehicle-treated rats that was absent in STZ-treated rats. Vehicle-treated rats displayed a nicotine-induced increase in ACh levels in the NAc (but not VTA), an effect that was lower in the NAc of STZ-treated rats. Insulin supplementation normalized the neurochemical effects of nicotine in the NAc and VTA of STZ-treated rats, suggesting that insulin modulates the neurochemical effects of nicotine in the mesolimbic pathway of STZ-treated rats. The goal of this study was to examine whether insulin modulates the neurochemical effects of nicotine in the mesolimbic pathway of diabetic rats. The results revealed that a lack of insulin suppressed nicotine-induced increases in dopamine transmission, an effect that was modulated via amino acid control of dopamine release in the cell body region of the mesolimbic pathway. Importantly, the neurochemical effects of nicotine were restored to control levels in hypoinsulinemic rats that received insulin supplementation. This work demonstrates that insulin is a key hormone that modulates the neurochemical effects of nicotine in the mesolimbic pathway.
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影响因子：
5.3
作者：
Hjelmstad, GO
通讯作者：
Hjelmstad, GO
影响因子：
3.3
作者：
KALIVAS, PW;CHURCHILL, L;KLITENICK, MA
通讯作者：
KLITENICK, MA
影响因子：
3.4
作者：
O'Dell, Laura E.;Natividad, Luis A.;Nazarian, Arbi
通讯作者：
Nazarian, Arbi
影响因子：
2.1
作者：
Akbarzadeh, A.;Norouzian, D.;Rad, B. Lame
通讯作者：
Rad, B. Lame
影响因子：
7.7
作者：
HU, RM;LEVIN, ER;FRANK, HJL
通讯作者：
FRANK, HJL