TRANSGENIC MODELS OF DOPAMINE, OPIOIDS AND DRUG ABUSE

精神兴奋剂药物与多巴胺转运体上的特定位点结合 阻断多巴胺的再摄取这会增加多巴胺的量 可用于结合突触后受体并影响分子 和细胞事件。垂体的中间叶有所有的 调查滥用药物之间相互作用的必要要素 和多巴胺能系统其中包括一个很好的特点， 多巴胺能神经支配，多巴胺再摄取机制，高密度的 多巴胺受体和组成型表达的靶基因， 前阿黑皮素（POMC），它被多巴胺抑制。我们将使用 转基因小鼠与巨大的中叶肿瘤，组织切片， a）研究POMC基因的调控 多巴胺配体和选定药物的表达和肽释放 和B）研究多巴胺配体和药物的作用， 转基因小鼠中POMC基因表达和肽释放的滥用 患有中叶肿瘤这些研究将提供细胞和 具有明确定义和可测量终点的动物模型进行评价 精神兴奋剂药物对多巴胺能神经传递的干扰。

Psychostimulant drugs bind to specific sites on the dopamine transporter and block dopamine reuptake. This increases the amount of dopamine available for binding to post-synaptic receptors and affecting molecular and cellular events. The intermediate lobe of the pituitary has all the necessary elements for investigating interactions between drugs of abuse and the dopaminergic system. These include a well characterized dopaminergic innervation, a dopamine reuptake mechanism, a high density of dopamine receptors and a constitutively expressed target gene, the proopiomelanocortin (POMC), which is suppressed by dopamine. We will use transgenic mice with massive intermediate lobe tumors, tissue slices and a melanotroph cell line to: a) study the regulation of POMC gene expression and peptide release by dopamine ligands and selected drugs iii vitro, and b) investigate the effects of dopamine ligands and drugs of abuse on POMC gene expression and peptide release in transgenic mice bearing intermediate lobe tumors. These studies will provide cellular and animal models with clearly defined and measurable endpoints to evaluate perturbation of dopaminergic neurotransmission by psychostimulant drugs.