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首页> 外文期刊>The European Journal of Neuroscience >Influence of chronic amphetamine treatment and acute withdrawal on serotonin synthesis and clearance mechanisms in the rat ventral hippocampus
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Influence of chronic amphetamine treatment and acute withdrawal on serotonin synthesis and clearance mechanisms in the rat ventral hippocampus

机译：慢性苯丙胺治疗和急性停药对大鼠腹侧海马5-羟色胺合成及清除机制的影响

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Amphetamine withdrawal in both humans and rats is associated with increased anxiety states, which are thought to contribute to drug relapse. Serotonin in the ventral hippocampus mediates affective behaviors, and reduced serotonin levels in this region are observed in rat models of high anxiety, including during withdrawal from chronic amphetamine. This goal of this study was to understand the mechanisms by which reduced ventral hippocampus serotonergic neurotransmission occurs during amphetamine withdrawal. Serotonin synthesis (assessed by accumulation of serotonin precursor as a measure of the capacity of in vivo tryptophan hydroxylase activity), expression of serotonergic transporters, and in vivo serotonergic clearance using in vivo microdialysis were assessed in the ventral hippocampus in adult male Sprague Dawley rats at 24 h withdrawal from chronic amphetamine. Overall, results showed that diminished extracellular serotonin at 24 h withdrawal from chronic amphetamine was not accompanied by a change in capacity for serotonin synthesis (in vivo tryptophan hydroxylase activity), or serotonin transporter expression or function in the ventral hippocampus, but instead was associated with increased expression and function of organic cation transporters (low-affinity, high-capacity serotonin transporters). These findings suggest that 24 h withdrawal from chronic amphetamine reduces the availability of extracellular serotonin in the ventral hippocampus by increasing organic cation transporter-mediated serotonin clearance, which may represent a future pharmacological target for reversing anxiety states during drug withdrawal. Amphetamine withdrawal in both humans and rats is associated with increased anxiety states, which are thought to contribute to drug relapse. Serotonin in the ventral hippocampus mediates affective behaviors, and reduced serotonin levels in this region are observed in rat models of high anxiety, including during withdrawal from chronic amphetamine. ? 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
机译：在人和大鼠中苯丙胺戒断都与焦虑状态增加有关，这被认为与药物复发有关。腹侧海马中的5-羟色胺介导情感行为，并且在高焦虑的大鼠模型中（包括从慢性苯丙胺戒断期间），该区域的5-羟色胺水平降低。这项研究的目的是了解在苯丙胺戒断期间减少腹侧海马血清素能神经传递的机制。在成年雄性Sprague Dawley大鼠的腹侧海马中评估5-羟色胺的合成（通过5-羟色胺前体的积累作为衡量体内色氨酸羟化酶活性的量来评估），5-羟色胺转运蛋白的表达和体内5-羟色胺清除率的体内微透析。从慢性苯丙胺戒断24小时。总体而言，结果表明，从慢性苯丙胺戒断24小时后，细胞外血清素的减少并不伴随血清素合成能力（体内色氨酸羟化酶活性）或血清素转运蛋白在腹侧海马中的表达或功能的改变，而是与增加有机阳离子转运蛋白（低亲和力，高容量的血清素转运蛋白）的表达和功能。这些发现表明，通过增加有机阳离子转运蛋白介导的5-羟色胺清除率，从慢性苯丙胺戒断24小时会降低腹侧海马中细胞外5-羟色胺的利用率，这可能代表了在撤药期间逆转焦虑状态的未来药理学目标。在人和大鼠中苯丙胺戒断都与焦虑状态增加有关，这被认为与药物复发有关。腹侧海马中的5-羟色胺介导情感行为，在高焦虑大鼠模型中（包括从慢性苯丙胺戒断期间），该区域的5-羟色胺水平降低。 ？ 2012年欧洲神经科学学会联合会和布莱克韦尔出版有限公司。

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