Campbell Una C, Lalwani Kush, Hernandez Lisa, Kinney Gene G, Conn P Jeffrey, Bristow Linda J
Department of Pharmacology, Merck Research Laboratories, San Diego, CA 92121, USA
Psychopharmacology (Berl). 2004 Sep;175(3):310-8. doi: 10.1007/s00213-004-1827-5.
Recent studies have shown that metabotropic glutamate receptor 5 (mGluR5) can modulate N-methyl-D-aspartate (NMDA) receptor function in vivo. For example, the mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) can potentiate PCP (phencyclidine)-evoked hyperactivity and PCP-induced disruptions in pre-pulse inhibition (PPI) in rats.
To extend these previous behavioral findings and determine whether the mGluR5 antagonist MPEP can modulate the disruptions in learning and memory induced by PCP in rats.
The effects of MPEP, alone and in combination with PCP, were evaluated in rats trained to perform a repeated acquisition procedure (learning) or a delayed non-matching to position (DNMTP) radial maze task (spatial memory).
In the repeated acquisition task, MPEP (0-10 mg/kg, IP) dose-dependently decreased response rates but had no effect on response accuracy. In contrast, PCP (0.625-1.25 mg/kg, SC) reduced response rate and response accuracy in a dose-dependent manner. Although MPEP (10 mg/kg, IP) had no effect when administered alone, the mGluR5 antagonist potentiated the disruptions in learning induced by a low dose of PCP (0.625 mg/kg, SC). In the DNMTP maze task, MPEP (0-10 mg/kg, IP) had no effect on spatial memory, whereas PCP (1.25-2.5 mg/kg, SC) produced a dose-dependent disruption. MPEP (10 mg/kg, IP) potentiated the impairments in memory induced by PCP (1.25 mg/kg, SC).
The mGluR5 antagonist, MPEP, potentiated the disruptions in learning and memory induced by PCP. These behavioral data extend previous behavioral findings and further suggest that mGluR5 can modulate NMDA receptor function in vivo.
近期研究表明，代谢型谷氨酸受体5（mGluR5）可在体内调节N-甲基-D-天冬氨酸（NMDA）受体功能。例如，mGluR5拮抗剂2-甲基-6-（苯乙炔基）吡啶（MPEP）可增强大鼠体内苯环利定（PCP）诱发的多动以及PCP诱导的前脉冲抑制（PPI）破坏。
扩展先前的行为学研究结果，并确定mGluR5拮抗剂MPEP是否能调节PCP诱导的大鼠学习和记忆障碍。
在经过训练以执行重复获取程序（学习）或延迟位置不匹配（DNMTP）放射状迷宫任务（空间记忆）的大鼠中，评估单独使用MPEP以及MPEP与PCP联合使用的效果。
在重复获取任务中，MPEP（0 - 10毫克/千克，腹腔注射）剂量依赖性地降低反应率，但对反应准确性无影响。相比之下，PCP（0.625 - 1.25毫克/千克，皮下注射）以剂量依赖性方式降低反应率和反应准确性。虽然单独给予MPEP（10毫克/千克，腹腔注射）时无作用，但mGluR5拮抗剂增强了低剂量PCP（0.625毫克/千克，皮下注射）诱导的学习障碍。在DNMTP迷宫任务中，MPEP（0 - 10毫克/千克，腹腔注射）对空间记忆无影响，而PCP（1.25 - 2.5毫克/千克，皮下注射）产生剂量依赖性破坏。MPEP（10毫克/千克，腹腔注射）增强了PCP（1.25毫克/千克，皮下注射）诱导的记忆损伤。
mGluR5拮抗剂MPEP增强了PCP诱导的学习和记忆障碍。这些行为学数据扩展了先前的行为学研究结果，并进一步表明mGluR5可在体内调节NMDA受体功能。
