Addiction is characterized by a compulsive pattern of drug seeking and consumption and a high risk of relapse after withdrawal that are thought to result from persistent adaptations within brain reward circuits. Drugs of abuse increase dopamine (DA) concentration in these brain areas, including the striatum, which shapes an abnormal memory trace of drug consumption that virtually highjacks reward processing. Long-term neuronal adaptations of gamma-aminobutyric acidergic striatal projection neurons (SPNs) evoked by drugs of abuse are critical for the development of addiction. These neurons form two mostly segregated populations, depending on the DA receptor they express and their output projections, constituting the so-called direct (D1 receptor) and indirect (D2 receptor) SPN pathways. Both SPN subtypes receive converging glutamate inputs from limbic and cortical regions, encoding contextual and emotional information, together with DA, which mediates reward prediction and incentive values. DA differentially modulates the efficacy of glutamate synapses onto direct and indirect SPN pathways by recruiting distinct striatal signaling pathways, epigenetic and genetic responses likely involved in the transition from casual drug use to addiction. Herein we focus on recent studies that have assessed psychostimulant-induced alterations in a cell-type-specific manner, from remodeling of input projections to the characterization of specific molecular events in each SPN subtype and their impact on long-lasting behavioral adaptations. We discuss recent evidence revealing the complex and concerted action of both SPN populations on drug-induced behavioral responses, as these studies can contribute to the design of future strategies to alleviate specific behavioral components of addiction.

中文翻译：

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从信号分子到电路和行为：细胞类型特异性适应纹状体中精神兴奋剂暴露

成瘾的特点是强迫性地寻求和吸毒，戒断后复发的风险很高，这被认为是由于大脑奖励回路中的持续适应所致。滥用药物会增加这些大脑区域的多巴胺 (DA) 浓度，包括纹状体，这形成了药物消费的异常记忆痕迹，实际上是在劫持奖励处理。由滥用药物引起的 γ-氨基丁酸能纹状体投射神经元 (SPN) 的长期神经元适应对于成瘾的发展至关重要。根据它们表达的 DA 受体及其输出预测，这些神经元形成两个主要分离的群体，构成所谓的直接（D1 受体）和间接（D2 受体）SPN 通路。两种 SPN 亚型都从边缘和皮层区域接收会聚的谷氨酸输入，编码上下文和情感信息，以及 DA，它介导奖励预测和激励值。DA 通过招募不同的纹状体信号通路、表观遗传和遗传反应，不同地调节谷氨酸突触对直接和间接 SPN 通路的功效，这些反应可能涉及从偶然吸毒到成瘾的转变。在此，我们专注于最近的研究，这些研究以细胞类型特定的方式评估了精神兴奋剂引起的改变，从输入预测的重塑到每个 SPN 亚型中特定分子事件的表征及其对长期行为适应的影响。