Neuroscience Group, Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA.
Eur J Neurosci. 2013 Feb;37(3):479-90. doi: 10.1111/ejn.12050. Epub 2012 Nov 14.
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.
安非他命戒断与人类和大鼠的焦虑状态增加有关，据认为这会导致药物复发。腹侧海马体中的血清素介导情感行为，在高焦虑大鼠模型中观察到该区域的血清素水平降低，包括在慢性安非他命戒断期间。这项研究的目的是了解在安非他命戒断期间腹侧海马体中血清素能神经传递减少的机制。在慢性安非他命戒断 24 小时后，通过评估腹侧海马体中的血清素合成（通过积累血清素前体来评估体内色氨酸羟化酶活性的能力）、血清素转运体的表达以及使用体内微透析评估的体内血清素清除率，评估成年雄性 Sprague Dawley 大鼠中的情况。总的来说，结果表明，慢性安非他命戒断 24 小时后，细胞外血清素减少并不伴有血清素合成能力（体内色氨酸羟化酶活性）或腹侧海马体中血清素转运体表达或功能的改变，而是与有机阳离子转运体（低亲和力、高容量血清素转运体）的表达和功能增加有关。这些发现表明，慢性安非他命戒断 24 小时后，通过增加有机阳离子转运体介导的血清素清除，减少了腹侧海马体中细胞外血清素的可用性，这可能代表了逆转药物戒断期间焦虑状态的未来药物靶点。
