This study examined whether insulin modulates the neurochemical effects of nicotine in the mesolimbic pathway of diabetic rats. The 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, GABA, glutamate, and acetylcholine (ACh) 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, and this effect 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 diabetic rats.

中文翻译：

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胰岛素恢复尼古丁对糖尿病大鼠中脑边缘通路的神经化学作用

本研究检查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) 以诱导低胰岛素血症。一部分经 STZ 治疗的大鼠被植入胰岛素颗粒，可迅速使血糖水平恢复正常。两周后，将透析探针植入伏隔核 (NAc) 和同侧腹侧被盖区 (VTA)。第二天，在基线期间收集透析液样本，然后在尼古丁全身给药后收集。在 VTA 内施用 γ-氨基丁酸 (GABA) _{A后还收集了样本}受体拮抗剂荷包牡丹碱。使用液相色谱/质谱法 (LC/MS) 评估多巴胺、GABA、谷氨酸和乙酰胆碱 (ACh) 水平。结果表明，载体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，经 STZ 治疗的大鼠在服用尼古丁后未显示 NAc 多巴胺的任何变化，这种影响可能与 NAc 和 VTA 中同时增加的 GABA 和谷氨酸水平降低有关。VTA 内给予荷包牡丹碱可增加载体治疗大鼠的 NAc 多巴胺，而这种作用在 STZ 治疗的大鼠中不存在。载体处理的大鼠表现出尼古丁诱导的 NAc（但不是 VTA）中 ACh 水平的增加，这种作用在 STZ 处理的大鼠的 NAc 中较低。