Rezayof Ameneh, Razavi Samira, Haeri-Rohani Ali, Rassouli Yassaman, Zarrindast Mohammad-Reza
School of Biology, University College of Science, University of Tehran, Tehran, Iran.
Eur Neuropsychopharmacol. 2007 Jan;17(1):24-31. doi: 10.1016/j.euroneuro.2006.02.003. Epub 2006 Mar 6.
In the present study, the effects of bilateral intra-hippocampal CA1 (intra-CA1) injections of GABA(A) receptor agonist and/or antagonist on the acquisition and expression of morphine-induced place preference in male Wistar rats have been investigated. The conditioning treatments with subcutaneous (s.c.) injections of different doses of morphine (0.5-7.5 mg/kg) induced a conditioned place preference (CPP) for the drug-associated place in a dose-dependent manner. Intra-CA1 administration of the GABA(A) receptor agonist, muscimol (0.25, 0.5 and 1 microg/rat) significantly inhibited the morphine (5 mg/kg, s.c.)-induced CPP. Intra-CA1 injections of different doses of the GABA(A) receptor antagonist, bicuculline (0.25, 0.5 and 1 microg/rat), in combination with an ineffective dose of morphine (0.5 mg/kg, s.c.) elicited a significant CPP. However, muscimol or bicuculline by themselves did not elicit any effect on place conditioning. Furthermore, the muscimol-induced inhibition of morphine response was reversed by bicuculline (1 microg/rat, intra-CA1) administration. On the other hand, the bilateral intra-CA1 injections of muscimol (0.25, 0.5 and 1 microg/rat) or bicuculline (0.5, 1 and 2 microg/rat) significantly decreased the expression of morphine-induced CPP. Intra-CA1 administration of different doses of muscimol or bicuculline had no effect on locomotor activity in the testing phase. Our data indicated that the GABA(A) receptors of the hippocampal CA1 regions may play an important role in the acquisition and expression of morphine-induced place preference.
在本研究中，已对雄性Wistar大鼠双侧海马CA1区（CA1区内）注射GABA(A)受体激动剂和/或拮抗剂对吗啡诱导的位置偏爱学习和表达的影响进行了研究。皮下注射不同剂量吗啡（0.5 - 7.5 mg/kg）进行条件化处理，以剂量依赖方式诱导出对药物相关位置的条件性位置偏爱（CPP）。CA1区内给予GABA(A)受体激动剂蝇蕈醇（0.25、0.5和1 μg/只大鼠）可显著抑制吗啡（5 mg/kg，皮下注射）诱导的CPP。CA1区内注射不同剂量的GABA(A)受体拮抗剂荷包牡丹碱（0.25、0.5和1 μg/只大鼠），与无效剂量的吗啡（0.5 mg/kg，皮下注射）联合使用时，可引发显著的CPP。然而，蝇蕈醇或荷包牡丹碱单独使用时对位置条件化没有任何影响。此外，荷包牡丹碱（1 μg/只大鼠，CA1区内注射）给药可逆转蝇蕈醇诱导的对吗啡反应的抑制作用。另一方面，双侧CA1区内注射蝇蕈醇（0.25、0.5和1 μg/只大鼠）或荷包牡丹碱（0.5、1和2 μg/只大鼠）可显著降低吗啡诱导的CPP的表达。CA1区内给予不同剂量的蝇蕈醇或荷包牡丹碱对测试阶段的运动活动没有影响。我们的数据表明，海马CA1区的GABA(A)受体可能在吗啡诱导的位置偏爱学习和表达中起重要作用。
