Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
Neuropsychopharmacology. 2013 Jun;38(7):1344-51. doi: 10.1038/npp.2013.32. Epub 2013 Jan 28.
Adolescence coincides with symptomatic onset of several psychiatric illnesses including schizophrenia and addiction. Excess limbic dopamine activity has been implicated in these vulnerabilities. We combined molecular and dynamic indices of dopamine neurotransmission to assess dopamine function in adolescent rats in two functionally distinct striatal subregions: nucleus accumbens (NAc) and dorsal striatum (DS). In adolescents, we find an overall reduction in dopamine availability selective to the DS. Dopamine release in the DS, but not in the NAc, was less responsive to amphetamine in adolescents compared to adults. The dopamine transporter (DAT) inhibitor, nomifensine, similarly inhibited basal and amphetamine-induced dopamine release in either regions of both the age groups, suggesting that the reduced effectiveness of amphetamine is not due to differences in DAT function. Furthermore, DAT and vesicular monoamine transporter-2 expressions were similar in the DS and NAc of adolescent rats. In contrast, expression of tyrosine hydroxylase (TH) was reduced in the DS, but not in the NAc, of adolescents compared to adults. Behaviorally, adolescents were less sensitive to amphetamine but more sensitive to a TH inhibitor. These data indicate that, in contrast to the general notion that dopamine is hyperactive in adolescents, there is diminished presynaptic dopamine activity in adolescents that is selective to the DS and may result from attenuated TH activity. Given recent reports of altered dopamine activity in associative/dorsal striatum of individuals at a clinically high risk of psychosis, our data further support the idea that dorsal, as opposed to ventral, regions of the striatum are a locus of vulnerability for psychosis.
青春期与几种精神疾病（包括精神分裂症和成瘾）的症状发作相吻合。边缘系统多巴胺活性过度与这些脆弱性有关。我们结合了多巴胺神经递质的分子和动态指标，以评估两个功能不同的纹状体亚区（伏隔核（NAc）和背侧纹状体（DS））中青少年大鼠的多巴胺功能。在青少年中，我们发现 DS 中多巴胺的可用性整体减少，而选择性地减少了 DS。与成年人相比，青少年时 DS 中的多巴胺释放对安非他命的反应较小，而 NAc 中的多巴胺释放则较小。多巴胺转运蛋白（DAT）抑制剂诺米芬辛（nomifensine）也同样抑制了两个年龄段的两个区域中的基础和安非他命诱导的多巴胺释放，这表明安非他命的效果降低不是由于 DAT 功能的差异所致。此外，在青少年大鼠的 DS 和 NAc 中，DAT 和囊泡单胺转运蛋白-2（VMAT2）的表达相似。相比之下，与成年人相比，青少年时 DS 中的酪氨酸羟化酶（TH）表达降低，但 NAc 中则没有。行为上，青少年对安非他命的敏感性较低，但对 TH 抑制剂的敏感性较高。这些数据表明，与普遍认为青少年时期多巴胺过度活跃的观点相反，青少年时期 DS 中存在多巴胺前体活性降低的情况，而且可能是由于 TH 活性降低所致。鉴于最近有报道称，在处于精神病高危状态的个体的关联/背侧纹状体中多巴胺活动发生改变，我们的数据进一步支持了这样的观点，即与腹侧纹状体相比，背侧纹状体是精神病易感性的部位。
