Presynaptic G Protein-Coupled Receptors: Gatekeepers of Addiction?
Presynaptic G Protein-Coupled Receptors: Gatekeepers of Addiction?
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DOI：
10.3389/fncel.2016.00264
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发表时间：
2016
影响因子：
5.3
通讯作者：
Lovinger DM
中科院分区：
文献类型：
--
作者：
Johnson KA;Lovinger DM
药物滥用和成瘾引起广泛的社会和公共卫生问题，药物作用和药物使用和滥用背后的神经生物学是一个深入研究的领域。滥用药物改变突触传递，这些行为有助于急性中毒以及滥用药物的慢性影响。大多数哺乳动物突触的传递涉及两种受体亚型的神经递质激活：介导快速突触反应的配体门控离子通道和具有较慢神经调节作用的G蛋白偶联受体（gpcr）。gpcr代表了参与神经系统功能几乎所有方面的神经递质受体的很大一部分。此外，这些受体是许多药物治疗药物的靶点。药物滥用直接或间接影响gpcr介导的神经调节，对中毒、药物服用和对长时间药物暴露、戒断和成瘾的反应具有重要影响。在gpcr中，有几种亚型参与突触前抑制，其中大多数与Gi/o类G蛋白偶联。越来越多的证据表明，这些突触前Gi/o偶联gpcr在滥用药物的行为以及与这些药物相关的行为中发挥重要作用。本文将回顾这一主题，特别强调三种神经递质受体，多巴胺（DA； D1-和d2样受体），内源性大麻素（eCBs； CB1受体）和谷氨酸（II组代谢谷氨酸（mGlu）受体）。重点是来自实验室动物模型的最新证据（以及一些人类证据），这些证据表明这些受体在许多滥用药物的急性和慢性影响中，以及在药物寻找和服用的控制中。药物靶向这些受体改变药物寻找行为的能力提高了使用靶向这些受体的化合物进行成瘾药物治疗的可能性。本文还讨论了这一主题，重点讨论了mGlu2正变构调制剂（PAMs）的发展。
Drug abuse and addiction cause widespread social and public health problems, and the neurobiology underlying drug actions and drug use and abuse is an area of intensive research. Drugs of abuse alter synaptic transmission, and these actions contribute to acute intoxication as well as the chronic effects of abused substances. Transmission at most mammalian synapses involves neurotransmitter activation of two receptor subtypes, ligand-gated ion channels that mediate fast synaptic responses and G protein-coupled receptors (GPCRs) that have slower neuromodulatory actions. The GPCRs represent a large proportion of neurotransmitter receptors involved in almost all facets of nervous system function. In addition, these receptors are targets for many pharmacotherapeutic agents. Drugs of abuse directly or indirectly affect neuromodulation mediated by GPCRs, with important consequences for intoxication, drug taking and responses to prolonged drug exposure, withdrawal and addiction. Among the GPCRs are several subtypes involved in presynaptic inhibition, most of which are coupled to the Gi/o class of G protein. There is increasing evidence that these presynaptic Gi/o-coupled GPCRs have important roles in the actions of drugs of abuse, as well as behaviors related to these drugs. This topic will be reviewed, with particular emphasis on receptors for three neurotransmitters, Dopamine (DA; D1- and D2-like receptors), Endocannabinoids (eCBs; CB1 receptors) and glutamate (group II metabotropic glutamate (mGlu) receptors). The focus is on recent evidence from laboratory animal models (and some evidence in humans) implicating these receptors in the acute and chronic effects of numerous abused drugs, as well as in the control of drug seeking and taking. The ability of drugs targeting these receptors to modify drug seeking behavior has raised the possibility of using compounds targeting these receptors for addiction pharmacotherapy. This topic is also discussed, with emphasis on development of mGlu2 positive allosteric modulators (PAMs).
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影响因子：
3.4
作者：
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通讯作者：
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作者：
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