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7-羟基-DPAT的行为效应完全归因于伏隔核壳中多巴胺D2受体的刺激;旋转行为。

Behavioural effects of 7-OH-DPAT are solely due to stimulation of dopamine D2 receptors in the shell of the nucleus accumbens; turning behaviour.

作者信息

Koshikawa N, Kitamura M, Kobayashi M, Cools A R

机构信息

Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan.

出版信息

Eur J Pharmacol. 1996 Jul 25;308(3):235-41. doi: 10.1016/0014-2999(96)00302-0.

Abstract

The goal of this study was to determine whether the dopamine D3 receptor in limbic structures plays a role in the shell-specific and dopamine-dependent display of turning behaviour in rats. When combined with the dopamine D1 receptor agonist (+/-)-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine-7,8-diol (SKF-38393, 5 micrograms), the putative dopamine D3 receptor agonist (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT, 1, 5 and 10 micrograms) elicited contralateral turning in a dose-dependent manner following unilateral injection into the shell, but not the core, of the nucleus accumbens. The turning pattern displayed was identical to that reported previously after intra-accumbens administration of the cocktail of SKF-38393 and the dopamine D2 receptor agonist quinpirole. The behaviour under study was dose-dependently attenuated by local administration of the dopamine D1 receptor antagonist R(+)-7-chloro-8-hydroxy-3- methyl-I-phroyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390: 10 and 100 ng), the dopamine D2 receptor antagonist domperidone (25 and 50 ng) or the dopamine D2/3 receptor antagonist l-sulpiride (5 and 25 ng). Combined blockade of both dopamine D1 and D2 receptors in the shell with a dose of either antagonist alone that produced just a moderate reduction (10 ng SCH 23390 and 50 ng domperidone) completely antagonized the turning behaviour elicited by the cocktail of SKF-38393 and 7-OH-DPAT. Replacing 7-OH-DPAT by another putative dopamine D3 receptor agonist,S(+)-(4aR, 10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4, 3-b]-1, 4-oxazin-9-ol (PD 128,907, 10 micrograms), in the cocktail did produce no turning behaviour at all. It is concluded that mesolimbic dopamine D3 receptors play no role in the dopamine-dependent and shell-specific turning behaviour: the contribution of 7-OH-DPAT in the cocktail of SKF-38393 and 7-OH-DPAT to the display of turning behaviour is solely due to its ability to activate dopamine D2 receptors.

摘要

本研究的目的是确定边缘系统结构中的多巴胺D3受体是否在大鼠壳核特异性及多巴胺依赖性的旋转行为表现中发挥作用。当与多巴胺D1受体激动剂(±)-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓-7,8-二醇(SKF-38393,5微克)联合使用时,假定的多巴胺D3受体激动剂(±)-7-羟基-N,N-二正丙基-2-氨基四氢萘(7-OH-DPAT,1、5和10微克)在单侧注射到伏隔核壳核而非核心后,以剂量依赖性方式引发对侧旋转。所表现出的旋转模式与先前报道的伏隔核内注射SKF-38393和多巴胺D2受体激动剂喹吡罗的混合物后的模式相同。所研究的行为通过局部给予多巴胺D1受体拮抗剂R(+)-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓(SCH 23390:10和100纳克)、多巴胺D2受体拮抗剂多潘立酮(25和50纳克)或多巴胺D2/3受体拮抗剂左旋舒必利(5和25纳克)而呈剂量依赖性减弱。用单独一剂仅产生适度降低作用的拮抗剂(10纳克SCH 23390和50纳克多潘立酮)联合阻断壳核中的多巴胺D1和D2受体,完全拮抗了SKF-38393和7-OH-DPAT混合物引发的旋转行为。在混合物中用另一种假定的多巴胺D3受体激动剂S(+)-(4aR,10bR)-3,4,4a,10b-四氢-4-丙基-2H,5H-[1]苯并吡喃并[4,3-b]-1,4-恶嗪-9-醇(PD 128,907,10微克)替代7-OH-DPAT,根本不会产生旋转行为。得出的结论是,中脑边缘多巴胺D3受体在多巴胺依赖性及壳核特异性旋转行为中不起作用:7-OH-DPAT在SKF-38393和7-OH-DPAT混合物中对旋转行为表现的作用完全归因于其激活多巴胺D2受体的能力。

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