Modulation and functions of dopamine receptor heteromers in drugs of abuse-induced adaptations

NEUROPHARMACOLOGY

卷:152

Review

Andrianarivelo, Andry^1,2,3  Saint-Jour, Estefani^1,2,3  Walle, Roman^4,5  Trifilieff, Pierre^4,5  Vanhoutte, Peter^1,2,3 

[1] INSERM, Inst Biol Paris Seine, Neurosci Paris Seine, UMR S 1130, F-75005 Paris, France

[2] CNRS, UMR 8246, Neurosci Paris Seine, F-75005 Paris, France

[3] UPMC Univ Paris 06, Sorbonne Univ, Neurosci Paris Seine, UM CR18, F-75005 Paris, France

[4] INRA, UMR 1286, Nutr & Integrat Neurobiol, F-33076 Bordeaux, France

[5] Univ Bordeaux, F-33076 Bordeaux, France

关键词: Addiction;    Striatum;    Dopamine;    Glutamate;    Signaling;    Receptor heteromers;   

DOI  :  10.1016/j.neuropharm.2018.12.003

来源: Elsevier

【 摘 要 】

Drug addiction is a chronic and relapsing disorder that leads to compulsive drug intake despite deleterious consequences. By increasing dopamine (DA) in the mesolimbic system, drugs of abuse hijack the brain reward circuitry, which is critical for the development of enduring behavioral alterations. DA mainly acts onto DA D1 (D1R) and D2 (D2R) receptor subtypes, which are positively and negatively coupled to adenylyl cyclase, respectively. Extensive research has aimed at targeting these receptors for the treatment of addiction, however this often results in unwanted side-effects due to the implication of DA receptors in numerous physiological functions. A growing body of evidence indicates that the physical interaction of DA receptors with other receptors can finely tune their function, making DA receptor heteromers promising targets for more specific treatment strategies. An increasing number of articles highlighted the ability of both D1R and D2R to form heteromers, however, most studies carried out to date stem from observations in heterologous systems and the biological significance of DA receptor heteromers in vivo is only emerging. We focused this review on studies that were able to provide insights into functions on D1R and D2R heteromers in drug-evoked adaptations and discuss the limitations of current approaches to study receptor heteromers in vivo. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.

【 授权许可】

Free