Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide Plays Critical Role in Psychostimulant-Induced Depression.
Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide Plays Critical Role in Psychostimulant-Induced Depression.
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DOI：
10.4062/biomolther.2018.141
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发表时间：
2018-09-01
影响因子：
3.7
通讯作者：
Oh KW
中科院分区：
文献类型：
--
作者：
Meng Q;Kim HC;Oh S;Lee YM;Hu Z;Oh KW
CART肽是一种广泛分布于中枢神经系统的神经递质。以前，一些报告表明，核内注射CART肽积极调制行为敏化诱导的精神兴奋剂和调节中皮质边缘多巴胺能通路。研究证实，CART肽对精神兴奋剂增强的多巴胺受体信号通路、钙/钙调素依赖性激酶信号通路和关键转录因子表达具有抑制作用。除了调节多巴胺受体相关通路外，CART肽还表现出与其他神经递质受体（如谷氨酸受体和γ-氨基丁酸受体）的复杂相互作用，这进一步解释了CART肽对精神兴奋剂增强的运动活性的抑制作用。最近，CART肽已被证明对戒断后的厌恶情绪和不受控制的药物寻求行为具有抗焦虑作用。此外，微量注射CART肽已被证明具有抗抑郁作用，这表明其在情绪调节和避免抑郁样行为中的潜在效用。在这篇综述中，我们讨论了神经回路中的CART通路及其与神经递质的相互作用与精神兴奋剂诱导的抑郁症。
Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter expressed in the central nervous systems. Previously, several reports demonstrated that nucleus accumbal-injected CART peptide positively modulated behavioral sensitization induced by psychostimulants and regulated the mesocorticolimbic dopaminergic pathway. It is confirmed that CART peptide exerted inhibitory effect on psychostimulant-enhanced dopamine receptors signaling, Ca2+/calmodulin-dependent kinase signaling and crucial transcription factors expression. Besides modulation of dopamine receptors-related pathways, CART peptide also exhibited elaborated interactions with other neurotransmitter receptors, such as glutamate receptors and γ-aminobutyric acid receptors, which further account for attribution of CART peptide to inhibition of psychostimulant-potentiated locomotor activity. Recently, CART peptide has been shown to have anxiolytic functions on the aversive mood and uncontrolled drug-seeking behaviors following drug withdrawal. Moreover, microinjection of CART peptide has been shown to have an anti-depressant effect, which suggests its potential utility in the mood regulation and avoidance of depression-like behaviors. In this review, we discuss CART pathways in neural circuits and their interactions with neurotransmitters associated with psychostimulant-induced depression.