Microinjection of CART (cocaine- and amphetamine-regulated transcript) peptide into the nucleus accumbens inhibits the cocaine-induced upregulation of dopamine receptors and locomotor sensitization
Microinjection of CART (cocaine- and amphetamine-regulated transcript) peptide into the nucleus accumbens inhibits the cocaine-induced upregulation of dopamine receptors and locomotor sensitization
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将 CART（可卡因和安非他明调节转录物）肽显微注射到伏隔核中可抑制可卡因诱导的多巴胺受体上调和运动敏化
DOI：
10.1016/j.neuint.2014.06.005
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发表时间：
2014-09-01
影响因子：
4.2
通讯作者：
Hu, Zhenzhen
中科院分区：
文献类型：
--
作者：
Peng, Qinghua;Sun, Xi;Hu, Zhenzhen
反复接触成瘾药物会增强多巴胺受体（DR）信号传导以及伏隔核（NAcc）中环腺苷5'-单磷酸（cAMP）反应元件结合蛋白（CREB）调节的可卡因和安非他明调节转录物（CART）表达的最终磷酸化。已知这些效应有助于行为敏感化的表达。 CART 肽是调节药物奖励和强化的神经肽。本实验研究了将 CART 55-102 微注射到 NAcc 中对 (1) CREB 磷酸化、(2) cAMP/蛋白激酶 A (PKA) 信号传导和 (3) 细胞外信号调节激酶 (ERK) 磷酸化激酶信号传导的影响。在这里，我们表明，向 NAcc 重复显微注射 CART 55-102 肽（1.0 或 2.5 μg，0.5 μl/侧）可减弱可卡因诱导的该位点 D1R、D2R 和 D3R 磷酸化的增强。此外，显微注射 CART 55-102，然后重复注射可卡因 (15 mg/kg)，剂量依赖性地阻断可卡因给药第五天的 cAMP 水平、PKA 活性以及 pERK 和 pCREB 水平的增强。为期 5 天的 CART 肽显微注射也抑制了可卡因诱导的大鼠运动活动和行为敏化。这些结果表明，CART 55-102 肽通过抑制 D1R 和 D2R 刺激、D3R 磷酸化、cAMP/PKA 信号传导和 ERK 磷酸化激酶信号传导，阻断 NAcc 中可卡因对 CREB 的磷酸化。这些效应可能对接受 CART 55-102 显微注射的大鼠的行为敏化起到了代偿性抑制作用。 (C) 2014 Elsevier Ltd. 保留所有权利。
Repeated exposure to addictive drugs enhances dopamine receptor (DR) signaling and the ultimate phosphoiylation of the cyclic adenosine 5'-monophosphate (cAMP)-response element-binding protein (CREB)-regulated cocaine- and amphetamine-regulated transcript (CART) expression in the nucleus accumbens (NAcc). These effects are known to contribute to the expression of behavioral sensitization. CART peptides are neuropeptides that modulate drug reward and reinforcement. The present experiments investigated the effects of CART 55-102 microinjection into the NAcc on (1) the phosphorylation of CREB, (2) cAMP/protein kinase A (PKA) signaling and (3) extracellular signal-regulated kinase (ERK) phosphorylated kinase signaling. Here, we show that repeated microinjections into the NAcc of CART 55-102 peptides (1.0 or 2.5 mu g, 0.5 mu l/side) attenuates cocaine-induced enhancements of D1R, D2R and D3R phosphorylation in this sites. Furthermore, the microinjection of CART 55-102 followed by repeated injections of cocaine (15 mg/kg) dose-dependently blocked the enhancement of cAMP levels, PKA activity and pERK and pCREB levels on the fifth day of cocaine administration. The cocaine-induced locomotor activity and behavioral sensitization in rats were also inhibited by the 5-day-microinjection of CART peptides. These results suggest that the phosphorylation of CREB by cocaine in the NAcc was blocked by the CART 55-102 peptide via the inhibition of D1R and D2R stimulation, D3R phosphorylation, cAMP/PKA signaling and ERK phosphorylated kinase signaling. These effects may have played a compensatory inhibitory role in the behavioral sensitization of rats that received microinjections of CART 55-102. (C) 2014 Elsevier Ltd. All rights reserved.