Response of limbic neurotensin systems to methamphetamine self-administration.
Response of limbic neurotensin systems to methamphetamine self-administration.
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DOI：
10.1016/j.neuroscience.2011.12.037
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发表时间：
2012-02-17
期刊：
影响因子：
3.3
通讯作者：
Frankel, P. S.
中科院分区：
文献类型：
--
作者：
Hanson, G. R.;Hoonakker, A. J.;Alburges, M. E.;McFadden, L. M.;Robson, C. M.;Frankel, P. S.
甲基苯丙胺（METH）滥用对个人和社会都是毁灭性的。虽然METH对多巴胺（DA）系统的影响可能有助于其高度成瘾性，但没有药物被批准用于治疗METH依赖。因此，我们和其他人已经研究了神经降压素（NT）系统的MET诱导的反应。神经降压素与DA投射的抑制性反馈作用相关，并且在用高剂量METH非偶然处理后，在中脑核和背侧纹状体中NT水平升高。在本研究中，我们采用了METH自我管理（SA）模型（链接到杠杆按压），以证明，替代NT激动剂的METH，而不显着影响运动活动，显着减少杠杆按压，但不是自我管理本身。我们还发现，大鼠自我管理METH（SAM）5个会议后，通过D1机制的脑桥核NT水平升高，与相应的负轭大鼠的影响较小。扩展（15天）METH SA暴露表现出类似的NT反应;然而，更详细的分析显示：（i）METH SA 15天显著升高了中脑核壳和背侧纹状体中的NT水平，但不升高中脑核核心中的NT水平，在相应的负轭METH大鼠中影响较小;（ii）在自我给药的METH大鼠中，背侧纹状体和背侧核壳中NT的升高与接受的METH总量显著相关，而在相应的轭合METH大鼠中则不相关;和（iii）NT激动剂阻断SAM大鼠在第15天的抗应激行为，但NT拮抗剂不改变。在SAM动物中5天后，NT水平在腹侧被盖区也升高，但在自我施用METH的大鼠的额叶皮质中没有升高。
Methamphetamine (METH) abuse is personally and socially devastating. Although effects of METH on dopamine (DA) systems likely contribute to its highly addictive nature, no medications are approved to treat METH dependence. Thus, we and others have studied the METH-induced responses of neurotensin (NT) systems. Neurotensin is associated with inhibitory feedback action on DA projections and NT levels are elevated in both the nucleus accumbens and dorsal striatum after non-contingent treatment with high doses of METH. In the present study we employed a METH self-administration (SA) model (linked to lever pressing) to demonstrate that substitution of a NT agonist for METH, while not significantly affecting motor activity, dramatically reduced lever pressing but was not self-administered per se. We also found that nucleus accumbens NT levels were elevated via a D1 mechanism after 5 sessions in rats self-administering METH (SAM), with a lesser effect in corresponding yoked rats. Extended (15 daily sessions) exposure to METH SA manifested similar NT responses; however, more detailed analyses revealed: (i) 15 d of METH SA significantly elevated NT levels in the nucleus accumbens shell and dorsal striatum, but not the nucleus accumbens core, with a lesser effect in the corresponding yoked METH rats; (ii) the elevation of NT in both the nucleus accumbens shell and dorsal striatum significantly correlated with the total amount of METH received in the self-administering, but not the corresponding yoked, METH rats; and (iii) a NT agonist blocked, but a NT antagonist did not alter, lever-pressing behavior on day 15 in SAM rats. After 5 days in SAM animals, NT levels were also elevated in the ventral tegmental area, but not frontal cortex of rats self-administering METH.
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影响因子：
4.2
作者：
HANSON, GR;SINGH, N;GIBB, JW
通讯作者：
GIBB, JW
影响因子：
4.7
作者：
Carlezon WA Jr;Thomas MJ
通讯作者：
Thomas MJ
影响因子：
2.9
作者：
ROBLEDO, P;MALDONADO, R;KOOB, GF
通讯作者：
KOOB, GF
DOI：
10.1124/jpet.110.176610
发表时间：
2011-03-01
影响因子：
3.5
作者：
Frankel, Paul S.;Hoonakker, Amanda J.;Hanson, Glen R.
通讯作者：
Hanson, Glen R.
影响因子：
3.4
作者：
CASTEL, MN;MORINO, P;HOKFELT, T
通讯作者：
HOKFELT, T