The hippocampus and cingulate cortex differentially mediate the effects of nicotine on learning versus on ethanol-induced learning deficits through different effects at nicotinic receptors.
The hippocampus and cingulate cortex differentially mediate the effects of nicotine on learning versus on ethanol-induced learning deficits through different effects at nicotinic receptors.
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DOI：
10.1038/npp.2009.45
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发表时间：
2009-08
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目前的研究探讨了尼古丁输注到背海马或前扣带对恐惧条件反射和乙醇诱导的恐惧条件反射缺陷的影响，以及这些影响是否涉及受体激活或失活。调节包括两次白色噪声（30秒，85 dB）-足部电击（2秒，0.57 mA）配对。在训练前15分钟向C57 BL/6小鼠施用盐水或乙醇，并且在训练前5分钟或在训练和测试前施用盐水或尼古丁。还测试了高亲和力烟碱乙酰胆碱能受体（nAChR）拮抗剂二氢-β-赤藓定（DHβE）调节乙醇和尼古丁效应的能力;在训练前或训练和测试前25分钟（注射）或15分钟（输注）给予生理盐水或DHβE。注入尼古丁到海马增强上下文恐惧条件反射，但乙醇诱导的学习障碍没有影响。将尼古丁注入前扣带回改善了乙醇诱导的背景和线索恐惧条件反射缺陷，但对乙醇未处理小鼠的学习没有影响。DHβE阻断了尼古丁对乙醇诱导的缺陷的影响;有趣的是，单独使用DH βE以及联合使用阈下剂量的DHβE和尼古丁也改善了乙醇诱导的缺陷，但未能增强学习能力。最后，DHβE未能改善乙醇诱导的β2 nAChR亚基敲除小鼠的缺陷。这些结果表明，尼古丁在海马中起作用，以增强上下文学习，但在扣带回中起作用，以改善乙醇诱导的学习缺陷，通过失活的高亲和力β2亚基含有nAChR。
The current study examined the effects of nicotine infusion into the dorsal hippocampus or anterior cingulate on fear conditioning and on ethanol-induced deficits in fear conditioning, and whether these effects involved receptor activation or inactivation. Conditioning consisted of two white noise (30 seconds, 85 dB)–foot shock (2 seconds, 0.57 mA) pairings. Saline or ethanol was administered to C57BL/6 mice 15 minutes before training and saline or nicotine was administered 5 minutes before training or before training and testing. The ability of the high-affinity nicotinic acetylcholinergic receptor (nAChR) antagonist dihydro-beta-erythroidine (DHβE) to modulate the effects of ethanol and nicotine was also tested; saline or DHβE was administered 25 (injection) or 15 (infusion) minutes before training or before training and testing. Infusion of nicotine into the hippocampus enhanced contextual fear conditioning but had no effect on ethanol-induced learning deficits. Infusion of nicotine into the anterior cingulate ameliorated ethanol-induced deficits in contextual and cued fear conditioning but had no effect on learning in ethanol-naïve mice. DHβE blocked the effects of nicotine on ethanol-induced deficits; interestingly, DHβE alone and co-administration of sub-threshold doses of DHβE and nicotine also ameliorated ethanol-induced deficits but failed to enhance learning. Finally, DHβE failed to ameliorate ethanol-induced deficits in β2 nAChR subunit knockout mice. These results suggest that nicotine acts in the hippocampus to enhance contextual learning, but acts in the cingulate to ameliorate ethanol-induced learning deficits through inactivation of high-affinity β2 subunit-containing nAChRs.
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影响因子：
4.1
作者：
Gould, TJ
通讯作者：
Gould, TJ
影响因子：
2.7
作者：
Gould, TJ;Higgins, JS
通讯作者：
Higgins, JS
影响因子：
56.9
作者：
Frankland, PW;Bontempi, B;Silva, AJ
通讯作者：
Silva, AJ
影响因子：
3.4
作者：
Gulick, Danielle;Gould, Thomas J.
通讯作者：
Gould, Thomas J.
影响因子：
7.3
作者：
Exley, R.;Cragg, S. J.
通讯作者：
Cragg, S. J.