CART peptide inhibits locomotor activity induced by simultaneous stimulation of D1 and D2 receptors, but not by stimulation of individual dopamine receptors.

CART peptide inhibits locomotor activity induced by simultaneous stimulation of D1 and D2 receptors, but not by stimulation of individual dopamine receptors.
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DOI:
10.1002/syn.20815
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发表时间:
2011-01
期刊:
影响因子:
2.3
通讯作者:
Kuhar, Michael J.
Kuhar, Michael J.
中科院分区:
医学4区
文献类型:
--
作者:
Moffett, Mark C.;Song, Jane;Kuhar, Michael J.

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CART(可卡因和安非他明调节转录)肽在奖励和强化中起调节作用。之前,我们的实验室证明,向伏隔核(NAc)注射CART肽(CART 55-102)可以减弱可卡因和多巴胺引起的运动活动(LMA)的增加,也可以减弱可卡因的奖励。本研究在雄性Sprague-Dawley大鼠伏隔区内注射CART肽对多巴胺受体激动剂诱导的LMA的影响。比较D1受体激动剂SKF-81297、生理盐水、CART 55-102或CART 55-102和SKF-81297联合使用的效果。联合使用CART可增强skf -81297诱导的LMA升高,而单独注射CART无明显作用。注射D2激动剂7-OH-DPAT对LMA无影响,7-OH-DPAT与CART肽联合使用也无影响。D3受体激动剂Quinelorane不会改变LMA, CART肽和Quinelorane的组合也不会改变LMA。接下来的实验检测了CART肽对D1激动剂SKF-81297和D2激动剂7-OH-DPAT共同注射诱导的LMA的影响。SKF-81297与7-OH-DPAT联用诱导的LMA大于SKF-81297单用诱导的LMA。CART肽与D1和D2激动剂联合使用可降低LMA。这些结果强烈表明,CART肽通过调节D1和D2多巴胺受体的同时激活来降低精神兴奋剂的作用,而不是通过影响任何单个多巴胺受体的作用。
CART (Cocaine- and amphetamine-regulated transcript) peptide has been implicated in playing a modulatory role in reward and reinforcement. Previously, our laboratory demonstrated that injections of CART peptide (CART 55–102) into the nucleus accumbens (NAc) attenuated both cocaine- and dopamine-induced increases in locomotor activity (LMA), and attenuated cocaine reward as well. In this study, the effects of CART peptide on LMA induced by dopamine receptor agonists were evaluated after intra-accumbal injections in male, Sprague-Dawley rats. Effects of the D1 receptor agonist, SKF-81297, saline, CART 55–102, or CART 55–102 and SKF-81297 together, were compared. The SKF-81297-induced increase in LMA was potentiated by co-administration of CART, while injection of CART alone had no significant effect. Injection of the D2 agonist, 7-OH-DPAT, had no effect on LMA, and the combination of both 7-OH-DPAT and CART peptide also had no effect. Quinelorane, a D3 receptor agonist, did not alter LMA, nor did the combination of CART peptide and quinelorane. The next experiment examined the effects of CART peptide on LMA induced by co-injection of both the D1 agonist, SKF-81297, and the D2 agonist, 7-OH-DPAT. The combination of SKF-81297 and 7-OH-DPAT induced greater LMA than SKF-81297 alone. Co-administration of CART peptide along with the D1 and D2 agonists reduced LMA. These results strongly suggest that CART peptide reduces the effects of psychostimulants by modulating the simultaneous activation of both D1 and D2 dopamine receptors, rather than by affecting the action of any individual dopamine receptor.
通过逆行标记鉴定纹状体投射神经元类型上 D1 和 D2 多巴胺受体的大鼠核周差异定位
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发表时间: 2006-12-01
影响因子: 2.8
作者:
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发表时间: 2008-10
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DOI: 10.1016/j.regpep.2007.07.003
发表时间: 2007-12-04
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作者:
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