Brown Robyn M, Short Jennifer L
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, 3052, Australia.
J Pharm Pharmacol. 2008 Nov;60(11):1409-30. doi: 10.1211/jpp/60.11.0001.
The specific events between initial presumably manageable drug intake and the development of a drug-addicted state are not yet known. Drugs of abuse have varying mechanisms of action that create a complex pattern of behaviour related to drug consumption, drug-seeking, withdrawal and relapse. The neuromodulator adenosine has been shown to play a role in reward-related behaviour, both as an independent mediator and via interactions of adenosine receptors with other receptors. Adenosine levels are elevated upon exposure to drugs of abuse and adenosine A(2A) receptors are enriched in brain nuclei known for their involvement in the processing of drug-related reinforcement processing. A(2A) receptors are found in receptor clusters with dopamine and glutamate receptors. A(2A) receptors are thus ideally situated to influence the signalling of neurotransmitters relevant in the neuronal responses and plasticity that underlie the development of drug taking and drug-seeking behaviour. In this review, we present evidence for the role of adenosine and A(2A) receptors in drug addiction, thereby providing support for current efforts aimed at developing drug therapies to combat substance abuse that target adenosine signalling via A(2A) receptors.
最初可能可控的药物摄入与药物成瘾状态发展之间的具体事件尚不清楚。滥用药物具有不同的作用机制，这些机制形成了与药物消费、觅药、戒断和复发相关的复杂行为模式。神经调质腺苷已被证明在与奖赏相关的行为中发挥作用，既作为独立的调节因子，也通过腺苷受体与其他受体的相互作用发挥作用。暴露于滥用药物时腺苷水平会升高，并且腺苷A(2A)受体在已知参与药物相关强化过程处理的脑核中富集。A(2A)受体存在于与多巴胺和谷氨酸受体的受体簇中。因此，A(2A)受体处于理想位置，可影响与神经元反应和可塑性相关的神经递质信号传导，而这些反应和可塑性是药物摄取和觅药行为发展的基础。在本综述中，我们提供了腺苷和A(2A)受体在药物成瘾中作用的证据，从而为目前旨在开发通过A(2A)受体靶向腺苷信号传导来对抗药物滥用的药物疗法的努力提供支持。
