Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens.
Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens.
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DOI：
10.1038/s42003-021-02358-w
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发表时间：
2021-07-16
影响因子：
5.9
通讯作者：
Calipari ES
中科院分区：
文献类型：
--
作者：
López AJ;Johnson AR;Euston TJ;Wilson R;Nolan SO;Brady LJ;Thibeault KC;Kelly SJ;Kondev V;Melugin P;Kutlu MG;Chuang E;Lam TT;Kiraly DD;Calipari ES
物质使用障碍（SUD）是一种慢性神经精神疾病，其特征是调节奖励和动机的神经回路的长期改变。大量的工作集中在表征神经功能和行为的这些持续变化的基础上的分子底物。然而，这项工作绝大多数集中在男性受试者，尽管越来越多的临床和临床前证据表明，女性表现出不同的进展SUD和滥用兴奋剂药物，如可卡因的反应。在这里，我们表明，性别是一个关键的生物变量，定义药物诱导的可塑性在核丘脑（NAc）。使用定量质谱法，我们评估了可卡因自我管理诱导的蛋白质表达模式，并证明了男性和女性之间独特的分子特征。我们表明，1。在雄性和雌性动物中，Cocaine自身给药诱导显著调节的蛋白质的非重叠蛋白质表达模式;重要的是，可卡因诱导的蛋白质调节差异与性别相互作用，以消除蛋白质组中的基础性二态性。最后，消除蛋白质组中的这些基线差异是伴随着消除非药物奖励行为中的性别差异。总之，这些数据表明，可卡因管理是能够重写基础蛋白质组功能和奖励相关的行为。López和约翰逊等人使用定量质谱法测量小鼠可卡因自我给药诱导的丘脑核中蛋白质表达的变化。他们证明了对雄性和雌性之间蛋白质表达的差异效应，消除了在基础条件下观察到的性别差异。
Substance use disorder (SUD) is a chronic neuropsychiatric condition characterized by long-lasting alterations in the neural circuitry regulating reward and motivation. Substantial work has focused on characterizing the molecular substrates that underlie these persistent changes in neural function and behavior. However, this work has overwhelmingly focused on male subjects, despite mounting clinical and preclinical evidence that females demonstrate dissimilar progression to SUD and responsivity to stimulant drugs of abuse, such as cocaine. Here, we show that sex is a critical biological variable that defines drug-induced plasticity in the nucleus accumbens (NAc). Using quantitative mass spectrometry, we assessed the protein expression patterns induced by cocaine self-administration and demonstrated unique molecular profiles between males and females. We show that 1. Cocaine self-administration induces non-overlapping protein expression patterns in significantly regulated proteins in males and females and 2. Critically, cocaine-induced protein regulation differentially interacts with sex to eliminate basal sexual dimorphisms in the proteome. Finally, eliminating these baseline differences in the proteome is concomitant with the elimination of sex differences in behavior for non-drug rewards. Together, these data suggest that cocaine administration is capable of rewriting basal proteomic function and reward-associated behaviors. López and Johnson et al. used quantitative mass spectrometry to measure changes in protein expression in the nucleus accumbens that were induced by cocaine self-administration in mice. They demonstrated differential effects on protein expression between males and females that eliminated the sex differences observed under basal conditions.
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影响因子：
4.6
作者：
Cahill KM;Huo Z;Tseng GC;Logan RW;Seney ML
通讯作者：
Seney ML
影响因子：
7.6
作者：
Kutlu, Munir Gunes;Zachry, Jennifer E.;Calipari, Erin S.
通讯作者：
Calipari, Erin S.
影响因子：
12.3
作者：
Feng J;Wilkinson M;Liu X;Purushothaman I;Ferguson D;Vialou V;Maze I;Shao N;Kennedy P;Koo J;Dias C;Laitman B;Stockman V;LaPlant Q;Cahill ME;Nestler EJ;Shen L
通讯作者：
Shen L
影响因子：
4.4
作者：
Herrero-Turrión MJ;Rodríguez-Martín I;López-Bellido R;Rodríguez RE
通讯作者：
Rodríguez RE
影响因子：
5.3
作者：
Hofford, Rebecca S.;Euston, Tanner J.;Kiraly, Drew D.
通讯作者：
Kiraly, Drew D.