Khan M A, Shoaib M
Neuroscience Branch, Addiction Research Center, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
Brain Res. 1996 May 6;719(1-2):198-202. doi: 10.1016/0006-8993(96)00028-5.
Current research has shown that manipulation at the glycine site of the NMDA receptor by various compounds can modulate NMDA receptor function and its behavioural consequences. The present study was conducted in order to neuroanatomically localize the effects of (+)-HA966 upon the acute and chronic effects of cocaine. Locomotor activity of Sprague-Dawley rats pretreated with (+)-HA966 (60 micrograms) into the nucleus accumbens five min prior to receiving cocaine (20 mg/kg i.p.) was significantly less than locomotor activity of the vehicle pretreated rats. Repeated treatment with cocaine resulted in sensitization to the locomotor stimulant effects of cocaine. Co-administration of (+)-HA966 with cocaine prevented the sensitization to a subsequent cocaine challenge, in which activity was comparable to levels of naive individuals given an acute injection of cocaine. These results suggest that the glycine site on NMDA receptors in the nucleus accumbens plays an important role in both the acute and sensitized responses to cocaine on locomotor activity.
目前的研究表明,各种化合物对NMDA受体甘氨酸位点的调控可调节NMDA受体功能及其行为后果。本研究旨在从神经解剖学角度定位(+)-HA966对可卡因急性和慢性影响的作用。在给Sprague-Dawley大鼠腹腔注射可卡因(20mg/kg)前5分钟,向其伏隔核注射(+)-HA966(60微克),预处理后的大鼠运动活性显著低于注射赋形剂预处理的大鼠。重复给予可卡因会导致对可卡因运动刺激作用的敏化。(+)-HA966与可卡因共同给药可防止对后续可卡因激发产生敏化,此时的活性与初次注射可卡因的未用药个体水平相当。这些结果表明,伏隔核中NMDA受体上的甘氨酸位点在对可卡因运动活性的急性和敏化反应中均起重要作用。