Walker P D, Capodilupo J G, Wolf W A, Carlock L R
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Brain Res. 1996 Sep 2;732(1-2):25-35. doi: 10.1016/0006-8993(96)00483-0.
The effects of lowered serotonin (5-hydroxytryptamine; 5-HT) neurotransmission on preprotachykinin (PPT) and preproenkephalin (PPE) mRNA levels were examined in subregions of the striatum. Adult male rats were treated systemically with para-chlorophenylalanine (pCPA; 350 mg/kg single i.p. injection) which reduced forebrain 5-HT amounts to approximately 20% of saline-injected controls at 24 and 48 h. As measured by Northern analysis, PPT and PPE mRNA levels were elevated 50% and 160% respectively in the anterior ventromedial striatum (region included nucleus accumbens). PPT mRNA levels were raised 90% in posterior striatum (at the level of the globus pallidus) by 48 h post-pCPA injection. To determine if increased PPT and PPE mRNA levels represented a transient response to brief 5-HT inhibition, additional experiments were performed to provide continual suppression of 5-HT within the striatum. First, rats received daily intraperitoneal injections of saline or the 5-HT1A receptor agonist, 8-OH-DPAT (1 mg/kg), for 7 days to reduce 5-HT release from raphestriatal terminals. In a parallel experiment, the serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT, 5 micrograms), was stereotaxically injected into the striatum as a means to permanently remove 5-HT terminals. Although levels of each mRNA species were differentially sensitive to 5,7-DHT or 8-OH-DPAT, PPT and PPE mRNAs were lowered between 30-55% within the anterior dorsolateral and ventromedial striatum. Although these results support previous studies suggesting an overall positive regulatory role of serotonin on striatal tachykinin biosynthesis, PPT and PPE gene regulation in certain striatal subregions may by differentially sensitive to lowered 5-HT neurotransmission. This suggestion is supported by observations that acute systemic stimulation of 5-HT2A/C receptors with DOI (7 mg/kg single i.p. injection) raised PPT and PPE mRNA levels within anterior dorsolateral (30-60%) and posterior (100-200%) striata, but not within the anterior ventromedial striatum.
研究了纹状体各亚区中血清素（5-羟色胺；5-HT）神经传递降低对前速激肽原（PPT）和前脑啡肽原（PPE）mRNA水平的影响。成年雄性大鼠全身注射对氯苯丙氨酸（pCPA；350mg/kg单次腹腔注射），在24小时和48小时时，其前脑5-HT含量降至注射生理盐水对照组的约20%。通过Northern分析测量，在前内侧纹状体（包括伏隔核的区域）中，PPT和PPE mRNA水平分别升高了50%和160%。在pCPA注射后48小时，后纹状体（苍白球水平）中的PPT mRNA水平升高了90%。为了确定PPT和PPE mRNA水平的升高是否代表对短暂5-HT抑制的短暂反应，进行了额外的实验以持续抑制纹状体内的5-HT。首先，大鼠连续7天每天腹腔注射生理盐水或5-HT1A受体激动剂8-OH-DPAT（1mg/kg），以减少来自中缝-纹状体终末的5-HT释放。在一项平行实验中，将血清素神经毒素5,7-二羟色胺（5,7-DHT，5微克）立体定向注射到纹状体中，作为永久去除5-HT终末的一种手段。尽管每种mRNA的水平对5,7-DHT或8-OH-DPAT的敏感性不同，但在前背外侧和内侧纹状体中，PPT和PPE mRNA降低了30 - 55%。尽管这些结果支持了先前的研究，表明血清素对纹状体速激肽生物合成具有总体正向调节作用，但某些纹状体亚区中的PPT和PPE基因调节可能对降低的5-HT神经传递具有不同的敏感性。这一观点得到了以下观察结果的支持：用DOI（7mg/kg单次腹腔注射）急性全身刺激5-HT2A/C受体可使前背外侧（30 - 60%）和后（100 - 200%）纹状体中的PPT和PPE mRNA水平升高，但在前内侧纹状体中则不然。
