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首页> 外文期刊>The European Journal of Neuroscience >Modulation of striatal dopamine dynamics by cocaine self-administration and amphetamine treatment in female rats
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Modulation of striatal dopamine dynamics by cocaine self-administration and amphetamine treatment in female rats

机译：Cocaine自主给药和雌性大鼠疗法治疗的纹状体多巴胺动态的调节

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Despite decades of research into the neurobiological basis of cocaine abuse, pharmacotherapeutic treatments for cocaine addiction have been largely ineffective. Converging evidence from preclinical research and from outpatient clinical trials suggest that treatment with amphetamine is efficacious in reducing cocaine intake. Although it has been suggested that amphetamine treatment reduces cocaine intake as an agonist replacement therapy, we have shown recently that multiple aspects of dopamine signaling are altered by cocaine self-administration and returned to pre-cocaine function by amphetamine treatment in the nucleus accumbens of male rats. Here, we sought to determine if these effects were also evident in female subjects, and across regions of the striatum. Female rats performed 5 days of cocaine self-administration (1.5 mg kg(-1) inj(-1), 40 inj/day) and were treated with a single amphetamine (0.56 mg/kg) or saline infusion 1 hr prior to killing. We then used ex vivo fast-scan cyclic voltammetry in the nucleus accumbens core or dorsolateral caudate-putamen to examine dopamine signaling and cocaine potency. We found that in the nucleus accumbens core, cocaine self-administration decreased dopamine uptake rate and cocaine potency, and both alterations were restored by amphetamine treatment. In the dorsolateral caudate-putamen, neither cocaine self-administration nor amphetamine treatment altered dopamine uptake; however, cocaine potency was decreased by self-administration and returned to control levels by amphetamine. Together, these findings support a role for amphetamine treatment for cocaine addiction outside of agonist replacement therapy, and suggest that the development of cocaine tolerance is similar across sexes.
机译：尽管对可卡因滥用的神经生物学基础几十年来，但可卡因成瘾的药物治疗方法在很大程度上是无效的。从临床前研究和门诊临床试验中融合了证据表明，在减少可卡因摄入量的情况下，用安非他明治疗是有效的。虽然已经提示，Amphetamine治疗减少可卡因摄入作为激动剂替代疗法，但我们最近显示了多巴胺信号传导的多个方面通过可卡因自我施用而改变，并通过在男性的细胞核中的安非他胺治疗返回到阅术前函数。老鼠。在这里，我们试图确定这些效果是否在女性受试者中也显而易见，并且跨越纹状体的区域。雌性大鼠进行5天可卡因自我管理（1.5毫克千克（-1），40次注射/天），并在杀死前用单一的amphetamine（0.56mg / kg）或盐水输注1小时处理。然后在核中使用前体内快速扫描循环伏安法核心或背侧尾巴腐烂，检查多巴胺信号和可卡因效力。我们发现，在核心核心核心中，可卡因自我给药降低了多巴胺摄取率和可卡因效力，并且通过安非他明治疗恢复了两种改变。在背侧的尾巴腐烂中，既不是可卡因自我管理也不是amphetamine治疗改变多巴胺摄取;然而，通过自我管理减少可卡因效力，并通过安非胺恢复对照水平。这些发现在一起，支持在激动剂替代疗法之外的可卡因成瘾的可卡因治疗的作用，并表明可卡因耐受性的发展在性别上是相似的。

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