Ikeda H, Akiyama G, Fujii Y, Minowa R, Koshikawa N, Cools A R
Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Neuropharmacology. 2003 Jan;44(1):81-7. doi: 10.1016/s0028-3908(02)00334-9.
The role of AMPA and NMDA receptors in the shell of the nucleus accumbens in turning behaviour of rats was investigated. Unilateral injection of the AMPA receptor agonist, AMPA (0.25, 0.4, 0.5 and 1 microg), into the shell of the nucleus accumbens dose-dependently produced contraversive pivoting, namely tight head-to-tail turning marked by abnormal hindlimb backward stepping, while injection of AMPA (0.5 microg) into the core produced only a marginal effect. This shell-specific AMPA effect was dose-dependently inhibited by the AMPA receptor antagonist, NBQX (1 and 10 ng), which alone did not produce turning behaviour. The AMPA-induced pivoting was also dose-dependently inhibited by the non-competitive NMDA receptor antagonist, MK-801 (0.1 and 0.5 microg). Neither MK-801 (0.1, 0.5 and 5 microg) nor the NMDA receptor agonist, NMDA (0.5 and 1 microg), injected unilaterally into the shell, produced turning behaviour. Unilateral injection of a mixture of dopamine D(1) (SKF 38393, 5 microg) and D(2) (quinpirole, 10 microg) receptor agonists into the shell has been found to elicit contraversive pivoting. The dopamine D(1)/D(2) receptor antagonist, cis-(Z)-flupentixol (1 and 10 microg), injected into the shell, in doses known to block dopamine D(1)/D(2) receptor-mediated pivoting, also significantly inhibited AMPA (0.5 microg)-induced pivoting. Moreover, both NBQX (1 and 10 ng) and MK-801 (0.1 and 0.5 microg), injected into the shell, significantly inhibited dopamine D(1)/D(2) receptor-mediated pivoting. It is therefore concluded that unilateral stimulation of AMPA receptors in the shell of the nucleus accumbens can elicit contraversive pivoting, and that both AMPA and dopamine D(1)/D(2) receptors play a critical role in shell-specific pivoting in contrast to NMDA receptors that at best play only a modulatory role.
研究了AMPA和NMDA受体在伏隔核壳部对大鼠转向行为的作用。向伏隔核壳部单侧注射AMPA受体激动剂AMPA（0.25、0.4、0.5和1微克）可剂量依赖性地产生对侧旋转，即表现为异常后肢向后迈步的紧密头尾旋转，而向伏隔核核心注射AMPA（0.5微克）仅产生轻微效应。AMPA受体拮抗剂NBQX（1和10纳克）可剂量依赖性地抑制这种壳部特异性的AMPA效应，NBQX单独注射不会产生转向行为。非竞争性NMDA受体拮抗剂MK-801（0.1和0.5微克）也可剂量依赖性地抑制AMPA诱导的旋转。单侧注射到壳部的MK-801（0.1、0.5和5微克）或NMDA受体激动剂NMDA（0.5和1微克）均未产生转向行为。已发现向伏隔核壳部单侧注射多巴胺D(1)（SKF 38393，5微克）和D(2)（喹吡罗，10微克）受体激动剂的混合物可引发对侧旋转。向伏隔核壳部注射已知能阻断多巴胺D(1)/D(2)受体介导的旋转的剂量的多巴胺D(1)/D(2)受体拮抗剂顺式-(Z)-氟哌噻吨（1和10微克），也能显著抑制AMPA（0.5微克）诱导的旋转。此外，向伏隔核壳部注射NBQX（1和10纳克）和MK-801（0.1和0.5微克）均能显著抑制多巴胺D(1)/D(2)受体介导的旋转。因此得出结论，单侧刺激伏隔核壳部的AMPA受体可引发对侧旋转，与NMDA受体至多仅起调节作用相反，AMPA和多巴胺D(1)/D(2)受体在壳部特异性旋转中起关键作用。
