Krug M, Matthies R, Wagner M, Brödemann R
Institute of Pharmacology and Toxicology, Medical Academy Magdeburg, Germany.
Eur J Pharmacol. 1993 Feb 16;231(3):355-61. doi: 10.1016/0014-2999(93)90110-4.
Long-term potentiation (LTP) of monosynaptically evoked field potentials (MEFP) in the dentate gyrus of freely moving rats following tetanization of the perforant pathway was investigated after peripheral application of substances which have been shown to influence NMDA receptor-mediated effects (dextromethorphan, methadone) as well as structurally related substances with similar antitussive effects (codeine, normethadone). The noncompetitive NMDA receptor antagonist MK 801 was also tested for comparison. Whereas under control conditions the field e.p.s.p. (excitatory postsynaptic potential) and the population spike of the MEFP were largely uninfluenced by these substances, different effects were seen after the induction of LTP. MK 801 (0.2 mg/kg i.p.) suppressed the induction of LTP of both the field e.p.s.p. and the population spike. Dextromethorphan (40 mg/kg i.p.) also prevented the potentiation of the field e.p.s.p. and the population spike, thus resembling MK 801 in its effect. Codeine (20 mg/kg i.p.), the levorotatory structural analogue of dextromethorphan had no effect. Methadone and normethadone did not influence the potentiation of the field e.p.s.p. or interfere with the induction of potentiation of the population spike but depressed its maintenance. The results obtained with MK 801 confirm those reported by others. Comparison of the effects of dextromethorphan with those of MK 801, suggests that there is a direct interaction with the NMDA receptor-ionophore complex. The effects of methadone and normethadone appear not to be linked to an interaction with opioid receptors, since naloxone did not influence the suppression of LTP caused by methadone. The possibility of interference with the NMDA receptor-ionophore complex is discussed.
在自由活动大鼠的齿状回中，对穿通通路进行强直刺激后，研究了单突触诱发场电位（MEFP）的长时程增强（LTP）。实验中，外周应用了已证实可影响NMDA受体介导效应的物质（右美沙芬、美沙酮）以及具有类似镇咳作用的结构相关物质（可待因、去甲美沙酮）。同时，为作比较，还测试了非竞争性NMDA受体拮抗剂MK 801。在对照条件下，这些物质对场兴奋性突触后电位（e.p.s.p.）和MEFP的群体峰电位影响不大，但在诱导LTP后则出现了不同的效应。MK 801（腹腔注射0.2mg/kg）抑制了场e.p.s.p.和群体峰电位的LTP诱导。右美沙芬（腹腔注射40mg/kg）也阻止了场e.p.s.p.和群体峰电位的增强，其作用类似于MK 801。右美沙芬的左旋结构类似物可待因（腹腔注射20mg/kg）则无此作用。美沙酮和去甲美沙酮不影响场e.p.s.p.的增强，也不干扰群体峰电位增强的诱导，但会抑制其维持。MK 801的实验结果证实了其他研究报告。右美沙芬与MK 801效应的比较表明，其与NMDA受体-离子通道复合物存在直接相互作用。美沙酮和去甲美沙酮的效应似乎与阿片受体相互作用无关，因为纳洛酮不影响美沙酮引起的LTP抑制。文中还讨论了干扰NMDA受体-离子通道复合物的可能性。
