Novel delta receptor expression in opioid tolerant/dependent neurons

阿片类药物，如吗啡和海洛因，作用于大脑中特定的分子靶点或受体。长期使用阿片类药物会导致大脑受体系统发生变化，大大降低这些药物的效果(耐受性)，并在停止使用时产生不良戒断综合征(身体依赖)。本提案将确定神经细胞中细胞功能的适应机制，这些机制对这些变化至关重要。特别是，我们已经确定了与阿片受体密切相关但不是海洛因或吗啡靶标的受体--Delta受体的敏感性增强。我们将确定长期使用吗啡后该受体活性增强的机制，以期尝试治疗方法来管理阿片成瘾者和慢性疼痛患者的耐受性和身体依赖。

Opioids such as morphine and heroin act on specific molecular targets, or receptors, in the brain. Long term use of opioids produce changes in brain receptor systems that greatly diminish the effects of these drugs (tolerance), as well as producing an adverse withdrawal syndrome on cessation of use (physical dependence). The present proposal will identify the mechanisms of adaptations in cellular function in nerve cells critical for these changes. In particular, we have identified enhanced sensitivity of receptor, the delta receptor, that is closely related to the opioid receptor but is not a target for heroin or morphine. We will identify the mechanisms of enhanced activity of this receptor after chronic use of morphine with a view to tergeting therapeutics to manage tolerance and physical dependence in opioid addicts and chronic pain patients.