Badie-Mahdavi H, Behrens M M, Rebek J, Bartfai T
The Scripps Research Institute, Harold L. Dorris Neurological Research Institute, Department of Neuropharmacology, 10550 North Torrey Pines Road, SR307, La Jolla, CA 92037, USA.
Neuropeptides. 2005 Jun;39(3):249-51. doi: 10.1016/j.npep.2004.12.010. Epub 2005 Mar 19.
The impairment of cognitive performance by galanin administration in rodents indicates a possible modulating effect of this neuropeptide on long-term potentiation (LTP) induction in the hippocampal formation. Galnon is a non-peptide, systemically active galanin receptor agonist which has been tested in feeding, seizure and forced swim task in in vivo rodent experimental models. Similarly to galanin (1-29) (i.c.v.), galnon (i.p.) has exhibited anticonvulsant effects in rats. We have investigated the effect of galnon on the synaptic transmission and plasticity in hippocampal dentate gyrus (DG) of C57Bl/6 mice and compared the galnon effects to the effect of galanin (1-29) and galmic, a non-peptide galanin receptor agonist. Similarly to galanin (1-29) and galmic, superfusion of galnon did not alter the input-output responses in DG. Administration of galnon (1 microM) significantly attenuated the LTP induction by 85.5 +/- 1% by 51 min after high frequency trains stimulation. This result was very similar to the effect of galanin (1-29) and galmic, which caused an 80 +/- 1.5% and 94 +/- 2% reduction in the level of field potentiation, respectively. The PPF responses, however, were not altered due to galnon superfusion which is in contrast to the effect of galanin (1-29) or galmic. In summary, these data indicate that the systemically active, non-peptide galanin receptor agonist, galnon can exert similar effects to galanin (1-29) in attenuation of DG LTP in mice.
在啮齿动物中,给予甘丙肽会损害认知能力,这表明这种神经肽可能对海马结构中的长时程增强(LTP)诱导具有调节作用。Galnon是一种非肽类、具有全身活性的甘丙肽受体激动剂,已在体内啮齿动物实验模型的进食、癫痫发作和强迫游泳任务中进行了测试。与甘丙肽(1-29)(脑室内注射)类似,Galnon(腹腔注射)在大鼠中也表现出抗惊厥作用。我们研究了Galnon对C57Bl/6小鼠海马齿状回(DG)突触传递和可塑性的影响,并将Galnon的作用与甘丙肽(1-29)和galmic(一种非肽类甘丙肽受体激动剂)的作用进行了比较。与甘丙肽(1-29)和galmic类似,Galnon的灌流并未改变DG中的输入-输出反应。在高频串刺激后51分钟,给予Galnon(1 microM)可使LTP诱导显著减弱85.5±1%。这一结果与甘丙肽(1-29)和galmic的作用非常相似,它们分别使场电位水平降低了80±1.5%和94±2%。然而,与甘丙肽(1-29)或galmic的作用相反,Galnon灌流并未改变强直后增强(PPF)反应。总之,这些数据表明,具有全身活性的非肽类甘丙肽受体激动剂Galnon在减弱小鼠DG区LTP方面可发挥与甘丙肽(1-29)类似的作用。