Kádár T, Telegdy G, Schally A V
Department of Pathophysiology, A. Szent-Györgyi Medical University, Szeged, Hungary.
Physiol Behav. 1992 Mar;51(3):601-5. doi: 10.1016/0031-9384(92)90186-6.
The neuropharmacological actions of the agonist analog D-Trp-6-LH-RH were investigated in several tests after intracerebroventricular (ICV) administrations to male rats. The doses applied were 10, 100 and 1000 ng/animal. In the open field the 1000 ng ICV dose of the peptide D-Trp-6-LH-RH suppressed the ambulation, rearing and grooming. In a combined catalepsy test, the 10 ng and 1000 ng dose of D-Trp-6-LH-RH increased the total duration of immobility. The LH-RH agonist inhibited stereotyped behavior induced by both apomorphine and amphetamine, and the effects of 100 and 1000 ng D-Trp-6-LH-RH were significant. Naloxone in a dose of 0.5 mg/kg IP totally abolished the inhibition of apomorphine-induced stereotypy by 1000 ng D-Trp-6-LH-RH, but the opiate antagonist did not influence amphetamine-induced stereotypy but significantly potentiated the inhibitory effect of 100 ng D-Trp-6-LH-RH. In the tail-flick test the latencies were significantly increased after D-Trp-6-LH-RH ICV, both 20 or 40 min after the injections. The peptide-induced analgesia was totally naloxone reversible. The results indicate that the agonist analog of LH-RH exert potent actions on the central nervous system, and the mechanism of effects may involve dopaminergic transmission and/or endogenous opiates.
将激动剂类似物D-色氨酸-6-促黄体生成素释放激素(D-Trp-6-LH-RH)经脑室注射(ICV)给予雄性大鼠后,在多项试验中研究了其神经药理学作用。给药剂量为10、100和1000 ng/只动物。在旷场试验中,1000 ng ICV剂量的肽D-Trp-6-LH-RH抑制了行走、竖毛和理毛行为。在一项联合僵住症试验中,10 ng和1000 ng剂量的D-Trp-6-LH-RH增加了不动时间的总时长。促黄体生成素释放激素激动剂抑制了阿扑吗啡和苯丙胺诱导的刻板行为,100和1000 ng D-Trp-6-LH-RH的作用显著。腹腔注射0.5 mg/kg剂量的纳洛酮完全消除了1000 ng D-Trp-6-LH-RH对阿扑吗啡诱导的刻板行为的抑制作用,但该阿片拮抗剂对苯丙胺诱导的刻板行为没有影响,却显著增强了100 ng D-Trp-6-LH-RH的抑制作用。在甩尾试验中,ICV注射D-Trp-6-LH-RH后,无论是注射后20分钟还是40分钟,潜伏期均显著延长。该肽诱导的镇痛作用完全可被纳洛酮逆转。结果表明,促黄体生成素释放激素的激动剂类似物对中枢神经系统有强效作用,其作用机制可能涉及多巴胺能传递和/或内源性阿片类物质。