Zhang Min, Ballard Michael E, Unger Liliane V, Haupt Andreas, Gross Gerhard, Decker Michael W, Drescher Karla U, Rueter Lynne E
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA.
Behav Brain Res. 2007 Aug 22;182(1):1-11. doi: 10.1016/j.bbr.2007.04.021. Epub 2007 May 1.
Rats treated with apomorphine and amphetamine display sensorimotor gating impairments, as measured by prepulse inhibition (PPI), and these impairments can be reversed by antipsychotic treatment. However, it remains unknown whether the dopamine (DA) D(3) receptor plays a role in mediating these effects on PPI, as none of these DA agonists or antipsychotics are exclusively selective at either D(2) or D(3) receptors. To address this question, the current study was designed to investigate whether antipsychotic drugs and selective D(3) antagonists could block the PPI-disruptive effects of PD 128907 (a preferential D(3) agonist) and apomorphine. We found that the effect of PD 128907 on PPI in rats could be antagonized by risperidone, clozapine, and the selective D(3) antagonists SB 277011 and A-691990, but not by raclopride or haloperidol, while the apomorphine-induced PPI deficit could be reversed by risperidone, clozapine and haloperidol, but not by SB 2770111 and A-691990. These results suggest that the D(3) receptor does not mediate apomorphine-induced disruption of PPI in rats, however, given the findings that PD 128907 elicited a PPI-disruptive effect that was blocked by selective D(3) antagonists, a role of D(3) receptor in mediating PPI in rats cannot be ruled out. The possible mechanisms of D(3) receptor involvement in PPI are discussed.
用阿扑吗啡和苯丙胺处理的大鼠表现出感觉运动门控障碍，这通过前脉冲抑制（PPI）来衡量，并且这些障碍可通过抗精神病药物治疗得到逆转。然而，多巴胺（DA）D(3)受体是否在介导这些对PPI的作用中发挥作用仍不清楚，因为这些DA激动剂或抗精神病药物都不是仅对D(2)或D(3)受体具有选择性。为了解决这个问题，本研究旨在调查抗精神病药物和选择性D(3)拮抗剂是否可以阻断PD 128907（一种优先的D(3)激动剂）和阿扑吗啡对PPI的破坏作用。我们发现，利培酮、氯氮平以及选择性D(3)拮抗剂SB 277011和A-691990可以拮抗PD 128907对大鼠PPI的影响，但雷氯必利或氟哌啶醇则不能，而阿扑吗啡诱导的PPI缺陷可被利培酮、氯氮平和氟哌啶醇逆转，但SB 277011和A-691990则不能。这些结果表明，D(3)受体并不介导阿扑吗啡诱导的大鼠PPI破坏，然而，鉴于PD 128907引起的PPI破坏作用被选择性D(3)拮抗剂阻断的发现，不能排除D(3)受体在介导大鼠PPI中的作用。本文讨论了D(3)受体参与PPI的可能机制。
