Jackson A, Brown G, Stephens D N
Laboratory of Experimental Psychology, School of Biological Sciences, University of Sussex, Falmer, Brighton, UK.
Psychopharmacology (Berl). 1996 Dec;128(3):320-7. doi: 10.1007/s002130050140.
The effects of the AMPA-receptor antagonists NBQX and GYKI 52466 were compared with those of the NMDA-receptor channel blocker dizocilpine in two drug discrimination tests. In the first, rats were trained to discriminate morphine (2 mg/kg) from saline and in the second, to discriminate ketamine (7 mg/kg) from saline, using a two-lever food reinforced method. NBQX (1-6 mg/kg) did not substitute for either morphine or ketamine, even at a dose which reduced response rates (6 mg/kg). Likewise, the noncompetitive antagonist GYKI 52466 (5 and 10 mg/kg) produced only saline lever responding in the ketamine trained rats. When tested in combination with the training drug, NBQX (4.5 mg/kg) did not alter the morphine generalisation gradient, and similarly, neither NBQX (3 mg/kg) nor GYKI 52466 (5 and 10 mg/kg) interacted with the ketamine cue. In contrast, dizocilpine (0.05 mg/kg) significantly disrupted discrimination of morphine and produced clear drug lever responding (0.0125-0.1 mg/kg) in ketamine trained rats. These results suggest that AMPA-receptor antagonists and non-competitive NMDA-antagonists have different stimulus properties.
在两项药物辨别试验中，将AMPA受体拮抗剂NBQX和GYKI 52466的作用与NMDA受体通道阻滞剂地佐环平的作用进行了比较。在第一项试验中，使用双杠杆食物强化法训练大鼠区分吗啡（2毫克/千克）和生理盐水；在第二项试验中，训练大鼠区分氯胺酮（7毫克/千克）和生理盐水。即使在降低反应率的剂量（6毫克/千克）下，NBQX（1 - 6毫克/千克）也不能替代吗啡或氯胺酮。同样，非竞争性拮抗剂GYKI 52466（5和10毫克/千克）在氯胺酮训练的大鼠中仅产生对生理盐水杠杆的反应。当与训练药物联合测试时，NBQX（4.5毫克/千克）不会改变吗啡的泛化梯度，同样，NBQX（3毫克/千克）和GYKI 52466（5和10毫克/千克）都不会与氯胺酮线索相互作用。相比之下，地佐环平（0.05毫克/千克）显著干扰了对吗啡的辨别，并在氯胺酮训练的大鼠中产生了明显的药物杠杆反应（0.0125 - 0.1毫克/千克）。这些结果表明，AMPA受体拮抗剂和非竞争性NMDA拮抗剂具有不同的刺激特性。
