MODULATION OF COCAINE SELF-ADMINISTRATION IN THE RAT THROUGH D-3 DOPAMINE-RECEPTORS
MODULATION OF COCAINE SELF-ADMINISTRATION IN THE RAT THROUGH D-3 DOPAMINE-RECEPTORS
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DOI：
10.1126/science.8099761
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发表时间：
1993-06-18
期刊：
影响因子：
56.9
通讯作者：
KOOB, GF
中科院分区：
文献类型：
--
作者：
CAINE, SB;KOOB, GF
可卡因的强化特性可能是由中枢神经系统的中皮质边缘多巴胺通路介导的，但并不是所有参与可卡因强化作用的多巴胺受体亚型都被清楚地识别出来。最近，D-3受体已被克隆，其在大脑中的分布已被发现相对局限于中脑多巴胺系统的边缘投射。d -3选择性化合物7-羟基-n， n-二-n-丙基-2-氨基四萘林（7-OHDPAT）和喹匹罗在非自我强化的剂量下能有效减少大鼠的可卡因自我给药。此外，三种多巴胺受体激动剂具有与D-3受体结合的亲和力，这与它们减少可卡因自我给药的相对效力高度相关。D-3受体可能参与了可卡因的强化作用，可能是开发新的药物治疗可卡因滥用的有用靶点。
The reinforcing properties of cocaine are probably mediated by the mesocorticolimbic dopamine pathways in the central nervous system, but not all of the dopamine receptor subtypes involved in cocaine's reinforcing actions have been clearly identified. Recently, the D-3 receptor has been cloned, and its distribution in the brain has been found to be relatively restricted to limbic projections of the midbrain dopamine system. The D-3-selective compounds 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT) and quinpirole potently decreased cocaine self-administration in the rat at doses that were not by themselves reinforcing. Moreover, three dopamine receptor agonists had affinities for binding to the D-3 receptor that correlated highly with their relative potencies in decreasing cocaine self-administration. The D-3 receptor may be involved in the reinforcing effects of cocaine and may be a useful target for the development of new pharmacotherapies for cocaine abuse.