The emergence of insulin resistance following a chronic high-fat diet regimen coincides with an increase in the reinforcing effects of nicotine in a sex-dependent manner.
The emergence of insulin resistance following a chronic high-fat diet regimen coincides with an increase in the reinforcing effects of nicotine in a sex-dependent manner.
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DOI：
10.1016/j.neuropharm.2021.108787
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发表时间：
2021-12-01
影响因子：
4.7
通讯作者：
O'Dell, Laura E.
中科院分区：
文献类型：
--
作者：
Cruz, Bryan;Ortegon, Sebastian;Giner, Priscilla;Matos-Ocasio, Felix;Rodriguez-Crespo, Andrea;Uribe, Kevin P.;Galindo, Kayla, I;Serafine, Katherine M.;Nazarian, Arbi;O'Dell, Laura E.
本研究评估了胰岛素抵抗对尼古丁增强作用的性别依赖效应。雌性和雄性大鼠分别接受8周的慢性高脂肪饮食（HFD）或常规饮食（RD）。然后给一部分大鼠注射诱导胰岛素抵抗的链脲佐菌素或链脲佐菌素（STZ; 25 mg/kg）。为了评估胰岛素抵抗，在注射胰岛素（0.75 U/kg）后15、30、60、120和180分钟测量血糖水平。9天后，在一个操作箱中给予大鼠延长静脉自我给药（IVSA）尼古丁（0.015、0.03、0.06 mg/kg），在那里它们自由地吃各自的食物，并对水给予反应。每个剂量的尼古丁给药4天，在它们的笼子里间歇性地禁食3天。在最后一次IVSA疗程后的第二天，比较给药（3.0 mg/kg）后的身体体征，以沉淀尼古丁戒断。结果显示，无论性别，单独使用HFD的大鼠在胰岛素抵抗或尼古丁摄入量方面没有变化。在接受STZ的hfd喂养的大鼠中观察到胰岛素抵抗，并且这种影响的程度在雄性比雌性更大。我们的主要发现是，与雄性相比，HFD + STZ雌性大鼠的尼古丁摄入量更多。最后，所有小组的戒断症状都是相似的。我们的研究结果表明，被诊断为胰岛素信号紊乱的女性，如糖尿病，由于这种药物的强化作用，更容易受到尼古丁的影响。
The present study assessed the sex-dependent effects of insulin resistance on the reinforcing effects of nicotine. Female and male rats received a chronic high-fat diet (HFD) or regular diet (RD) for 8 weeks. A subset of rats then received vehicle or a dose of streptozotocin (STZ; 25 mg/kg) that induces insulin resistance. To assess insulin resistance, glucose levels were measured 15, 30, 60, 120, and 180 min after an insulin injection (0.75 U/kg). Nine days later, the rats were given extended access to intravenous self-administration (IVSA) of nicotine (0.015, 0.03, 0.06 mg/kg) in an operant box where they consumed their respective diet ad libitum and performed responses for water deliveries. Each nicotine dose was delivered for 4 days with 3 intermittent days of abstinence in their home cage. The day after the last IVSA session, physical signs were compared following administration of mecamylamine (3.0 mg/kg) to precipitate nicotine withdrawal. The results revealed that there were no changes in insulin resistance or nicotine intake in HFD alone rats regardless of sex. Insulin resistance was observed in HFD-fed rats that received STZ, and the magnitude of this effect was greater in males versus females. Our major finding was that nicotine intake was greater among HFD + STZ female rats as compared to males. Lastly, the physical signs of withdrawal were similar across all groups. Our results suggest that females diagnosed with disorders that disrupt insulin signaling, such as diabetes may be at risk of greater vulnerability to nicotine use due to enhanced reinforcing effects of this drug.
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影响因子：
5.6
作者：
Chen H;Saad S;Sandow SL;Bertrand PP
通讯作者：
Bertrand PP
影响因子：
4.7
作者：
Cruz B;Carcoba LM;Flores RJ;Espinoza EJ;Nazarian A;O'Dell LE
通讯作者：
O'Dell LE
影响因子：
4.8
作者：
Alexanderson, Camilla;Eriksson, Elias;Holmaeng, Agneta
通讯作者：
Holmaeng, Agneta
影响因子：
--
作者：
Al-Delaimy, WK;Manson, JE;Hu, FB
通讯作者：
Hu, FB
DOI：
10.1016/j.pnpbp.2015.06.005
发表时间：
2016-02-04
影响因子：
5.6
作者：
O'Dell, Laura E.;Nazarian, Arbi
通讯作者：
Nazarian, Arbi