Stevens K E, Kem W R, Mahnir V M, Freedman R
Medical Research Service, Veterans Affairs Medical Center, Denver, CO 80262, USA.
Psychopharmacology (Berl). 1998 Apr;136(4):320-7. doi: 10.1007/s002130050573.
Abnormal sensory inhibition is a measurable indicator of a sensory processing deficit which is observed in schizophrenia, and other disorders, and which may be heritable. This deficit has also been observed in certain inbred mouse strains where the intensity of the deficit has been correlated with reduction in the number of hippocampal alpha-bungarotoxin-sensitive nicotinic receptors. Nicotine and certain nicotinic agonists produce brief periods of normal sensory inhibition in these mice. Similarly, nicotine also transiently normalizes sensory inhibition in schizophrenics. The present study assessed the effects of a novel nicotinic partial agonist (GTS-21), selective for the alpha-bungarotoxin site, on sensory inhibition in DBA mice, a strain with no sensory inhibition under routine experimental conditions. GTS-21 produced a dose-dependent normalization of sensory inhibition which was blocked by alpha-bungarotoxin but not mecamylamine. In contrast to other nicotinic agonists, normalization of sensory inhibition by GTS-21 and two related anabaseine compounds, DMAB-anabaseine and DMAC-anabaseine, was observed when administered a second time to the animal, after a 40-min delay. Our results indicated that the anabaseine compounds increase sensory inhibition through alpha7 nicotinic receptors, and that their ability to act repeatedly on these receptors may be less affected by desensitization.
异常感觉抑制是感觉处理缺陷的一个可测量指标，在精神分裂症和其他疾病中可观察到，且可能具有遗传性。在某些近交系小鼠中也观察到了这种缺陷，缺陷的严重程度与海马中α-银环蛇毒素敏感的烟碱型受体数量减少相关。尼古丁和某些烟碱型激动剂能使这些小鼠产生短暂的正常感觉抑制。同样，尼古丁也能使精神分裂症患者的感觉抑制短暂恢复正常。本研究评估了一种对α-银环蛇毒素位点具有选择性的新型烟碱型部分激动剂（GTS-21）对DBA小鼠感觉抑制的影响，该品系在常规实验条件下无感觉抑制。GTS-21使感觉抑制呈剂量依赖性恢复正常，这种作用被α-银环蛇毒素阻断，但不受美加明阻断。与其他烟碱型激动剂不同，在对动物延迟40分钟后再次给予GTS-21以及两种相关的无碱基化合物DMAB-无碱基和DMAC-无碱基时，观察到感觉抑制恢复正常。我们的结果表明，无碱基化合物通过α7烟碱型受体增强感觉抑制，并且它们反复作用于这些受体的能力可能较少受到脱敏的影响。
