Ikemoto S, Glazier B S, Murphy J M, McBride W J
Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
J Neurosci. 1997 Nov 1;17(21):8580-7. doi: 10.1523/JNEUROSCI.17-21-08580.1997.
The objectives of this study were to examine the involvement of D1 and D2 receptors within the nucleus accumbens (ACB) in mediating reinforcement. The intracranial self-administration (ICSA) of D1 and D2 agonists was used to determine whether activating D1 and/or D2 receptors within the ACB of Wistar rats is reinforcing. At concentrations of 0.25, 0.50, and 1.0 mM (25, 50, and 100 pmol/100 nl of infusion), neither the D1 agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol [SKF 38393 (SKF)] hydrochloride nor the D2 agonist (-)-quinpirole (Quin) hydrochloride was self-administered into the shell region of the ACB. On the other hand, equimolar mixtures of SKF and Quin (SKF+Quin), at concentrations of 0.25, 0.50, and 1.0 mM each, were significantly self-infused into the ACB shell. The core region of the ACB did not support the ICSA of SKF+Quin at any of these concentrations. Rats increased lever pressing when the response requirement was increased from a fixed ratio 1 (FR1) to FR3, and they responded significantly more on the infusion lever than they did on the control lever. Coadministration of either 0.50 mM R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine (SCH 23390) hydrochloride, a D1 antagonist, or 0.50 mM S(-)-sulpiride, a D2 antagonist, completely abolished the ICSA of the mixture of SKF+Quin (each at 0.50 mM) into the ACB shell. The present results suggest that concurrent activation of D1- and D2-type receptors in the shell of the ACB had a cooperative effect on DA-mediated reward processes.
本研究的目的是检测伏隔核（ACB）内的D1和D2受体在介导强化作用中的参与情况。使用D1和D2激动剂的颅内自我给药（ICSA）来确定激活Wistar大鼠ACB内的D1和/或D2受体是否具有强化作用。在浓度为0.25、0.50和1.0 mM（25、50和100 pmol/100 nl输注量）时，D1激动剂盐酸R(+)-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓-7,8-二醇[SKF 38393（SKF）]和D2激动剂盐酸(-)-喹吡罗（Quin）均未被自我给药至ACB的壳区。另一方面，SKF和Quin（SKF+Quin）的等摩尔混合物，各自浓度为0.25、0.50和1.0 mM时，被显著自我注入ACB壳区。在这些浓度下，ACB的核心区域均不支持SKF+Quin的ICSA。当反应要求从固定比率1（FR1）增加到FR3时，大鼠的杠杆按压次数增加，并且它们在输注杠杆上的反应明显多于在对照杠杆上的反应。共同给予0.50 mM盐酸D1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）或0.50 mM D2拮抗剂S(-)-舒必利，可完全消除SKF+Quin混合物（各为0.50 mM）向ACB壳区的ICSA。目前的结果表明，ACB壳区内D1型和D2型受体的同时激活对多巴胺介导的奖赏过程具有协同作用。
