Pranzatelli M R, Huang Y Y, Dollison A M, Stanley M
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Brain Res Dev Brain Res. 1989 Nov 1;50(1):89-99. doi: 10.1016/0165-3806(89)90128-4.
Rat pups were injected intracisternally (i.c.) or intraperitoneally (i.p.) with 5,7-dihydroxytryptamine (5,7-DHT) or saline and challenged 2 and 14 weeks later with the 5-HT precursor 5-hydroxytryptophan (5-HTP), which evokes behavioral supersensitivity in adult rats, 5,7-DHT induced transient postinjection convulsions in rats injected i.c. but not i.p. Rats with either type of 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP. However, rats lesioned by i.p. injections exhibited significantly greater shaking behavior (+1445%) in response to 5-HTP than their i.c. counterparts, who instead showed more forepaw myoclonus (+250%) and head weaving (+270%), the core features of the 5-HT syndrome. Differences in 5-HT syndrome behaviors were already present 2 weeks after lesioning, whereas the difference in shaking behavior was not. After 14 weeks, 5-HT was selectively depleted (-43 to -92%) in hippocampus, spinal cord, and frontal cortex, and differences between i.c. and i.p. 5,7-DHT routes were insignificant except in frontal cortex. Brainstem 5-HT concentrations were significantly increased (+35%) after i.p. 5,7-DHT injections in contrast to reduction (-89%) after i.c. 5,7-DHT; 5-hydroxyindole acetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratios were decreased (-20%) with either route. These data suggest that brainstem 5-HT hyperinnervation following i.p. 5,7-DHT injection modifies the functional consequences of injury in abating the 5-HT syndrome, but does not result in complete recovery since shaking behavior is enhanced. Loss of presynaptically mediated autoregulation or receptor dysregulation may play a major role in behavioral supersensitivity induced by 5-HTP in rats with 5,7-DHT lesions. To the extent that the 5-HT syndrome is mediated by 5-HT1A receptors and shaking behavior by 5-HT2 sites, differential responses to injury of 5-HT1A and 5-HT2 receptors may contribute to these behavioral differences.
给新生大鼠脑池内（i.c.）或腹腔内（i.p.）注射5,7 - 二羟基色胺（5,7 - DHT）或生理盐水，并在2周和14周后用5 - 羟色胺前体5 - 羟色氨酸（5 - HTP）进行激发试验，5 - HTP可诱发成年大鼠的行为超敏反应。脑池内注射5,7 - DHT会使大鼠在注射后出现短暂惊厥，而腹腔内注射则不会。两种类型的5,7 - DHT损伤的大鼠对5 - HTP均表现出超敏行为反应。然而，腹腔内注射造成损伤的大鼠对5 - HTP的反应表现出显著更强的颤抖行为（增加1445%），相比之下，脑池内注射造成损伤的大鼠则表现出更多的前爪肌阵挛（增加250%）和头部摆动（增加270%），这些是5 - 羟色胺综合征的核心特征。5 - 羟色胺综合征行为差异在损伤后2周就已出现，而颤抖行为差异则未出现。14周后，海马体、脊髓和额叶皮质中的5 - 羟色胺被选择性耗竭（减少43%至92%），除额叶皮质外，脑池内和腹腔内注射5,7 - DHT途径之间的差异不显著。与脑池内注射5,7 - DHT后5 - 羟色胺减少（89%）相反，腹腔内注射5,7 - DHT后脑干5 - 羟色胺浓度显著增加（35%）；两种途径的5 - 羟基吲哚乙酸/5 - 羟色胺（5 - HIAA/5 - HT）比值均降低（20%）。这些数据表明，腹腔内注射5,7 - DHT后脑干5 - 羟色胺的超神经支配改变了损伤的功能后果，减轻了5 - 羟色胺综合征，但由于颤抖行为增强，并未导致完全恢复。突触前介导的自身调节丧失或受体失调可能在5,7 - DHT损伤的大鼠中由5 - HTP诱导的行为超敏反应中起主要作用。就5 - 羟色胺综合征由5 - HT1A受体介导，颤抖行为由5 - HT2位点介导而言，5 - HT1A和5 - HT2受体对损伤的不同反应可能导致了这些行为差异。
