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首页> 外文期刊>Addiction biology >Differences in regional cerebral blood flow response to a 5HT3 antagonist in early- and late-onset cocaine-dependent subjects
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Differences in regional cerebral blood flow response to a 5HT3 antagonist in early- and late-onset cocaine-dependent subjects

机译：早期和晚期可卡因依赖性受试者对5HT3拮抗剂的局部脑血流反应的差异

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5-hydroxytryptamine 3 (5HT3) receptors are important modulators of mesostriatal dopaminergic transmission and have been implicated in the pathophysiology of cocaine reward, withdrawal and self-administration. In addition, the 5HT3 antagonist ondansetron is effective in treating early-onset, but not late-onset, alcohol-dependent subjects. To explore the role of 5HT3 receptor systems in cocaine addiction using functioning imaging, we administered ondansetron to 23 abstinent, treatment-seeking cocaine-addicted and 22 sex-, age- and race-matched healthy control participants. Differences between early- (first use before 20 years, n = 10) and late-onset (first use after 20 years, n = 10) cocaine-addicted subjects were also assessed. On two separate days, subjects were administered ondansetron (0.15 mg/kg intravenously over 15 minutes) or saline. Regional cerebral blood flow (rCBF) was measured following each infusion with single photon emission computed tomography. No significant rCBF differences between the cocaine-addicted and control participants were observed following ondansetron relative to saline. Early-onset subjects, however, showed increased (P < 0.001) right posterior parahippocampal rCBF following ondansetron. In contrast, late-onset subjects showed decreased rCBF following ondansetron in an overlapping region of the right parahippocampal/ hippocampal gyrus. Early-onset subjects also displayed increased rCBF in the left anterior insula and subthalamic nucleus following ondansetron; late-onset subjects showed decreased rCBF in the right anterior insula. These findings suggest that the age of drug use onset is associated with serotonergic biosignatures in cocaine-addicted subjects. Further clarification of these alterations may guide targeted treatment with serotonergic medications similar to those successfully used in alcohol-dependent patients.
机译：5-羟色胺3（5HT3）受体是中鼻道多巴胺能传递的重要调节剂，并且与可卡因奖赏，戒断和自我给药的病理生理有关。此外，5HT3拮抗剂恩丹西酮可有效治疗早发型而非酒精依赖型受试者。为了使用功能性成像探讨5HT3受体系统在可卡因成瘾中的作用，我们向23名戒断，寻求治疗可卡因的成瘾者和22名性别，年龄和种族匹配的健康对照参与者施用了恩丹西酮。还评估了早期（20年之前首次使用，n = 10）和晚发型（20年之后首次使用，n = 10）可卡因上瘾的受试者之间的差异。在独立的两天中，向受试者施用恩丹西酮（在15分钟内静脉注射0.15 mg / kg）或盐水。每次输注后用单光子发射计算机断层扫描测量局部脑血流量（rCBF）。恩丹西酮组相对于生理盐水后，在可卡因成瘾者和对照参与者之间未观察到明显的rCBF差异。然而，早期发作的受试者在恩丹西酮后显示出右海马后旁rCBF增加（P <0.001）。相比之下，迟发受试者在右西海马/海马回的重叠区域中在恩丹西酮后显示出rCBF降低。早期发作的受试者在恩丹西酮后还显示左前岛和丘脑下核的rCBF增加。迟发性受试者显示右前岛的rCBF降低。这些发现表明，在可卡因成瘾的受试者中，开始使用药物的年龄与血清素能的生物特征有关。对这些改变的进一步阐明可以指导血清素能药物的靶向治疗，类似于在酒精依赖患者中成功使用的药物。

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