Hechler V, Gobaille S, Bourguignon J J, Maitre M
Centre de Neurochemie du CNRS, Strasbourg, France.
J Neurochem. 1991 Mar;56(3):938-44. doi: 10.1111/j.1471-4159.1991.tb02012.x.
The modification of dopamine release and accumulation induced by gamma-hydroxybutyrate (GHB) was studied using both striatal slices and in vivo microdialysis of caudate-putamen. GHB inhibited dopamine release for approximately 5-10 min in vitro, and this was associated with an accumulation of dopamine in the tissue. Subsequently, there was an increase in dopamine release. In the microdialysis experiments, low doses of GHB inhibited dopamine release, whereas higher doses strongly increased release; the initial decrease seen in slices could not be detected in vivo. Thus, GHB had a biphasic effect on the release of dopamine: An initial decrease in the release of transmitter was followed by an increase. A time-dependent biphasic effect was observed when GHB was added to brain slices, and a dose-dependent biphasic effect was seen in dialysate after systemic administration of GHB. Naloxone blocked GHB-induced dopamine accumulation and release both in vitro and in vivo. GHB also increased the release of opioid-like substances in the striatum. A specific antagonist of GHB receptors completely blocked both the dopamine response and the release of opioid-like substances. These data suggest that GHB increases dopamine release via specific receptors that may modulate the activity of opioid interneurons.
利用纹状体切片和尾状核-壳核的体内微透析技术，研究了γ-羟基丁酸（GHB）对多巴胺释放和积累的影响。在体外，GHB抑制多巴胺释放约5 - 10分钟，这与组织中多巴胺的积累有关。随后，多巴胺释放增加。在微透析实验中，低剂量的GHB抑制多巴胺释放，而高剂量则强烈增加释放；在切片中观察到的最初减少在体内未被检测到。因此，GHB对多巴胺释放具有双相作用：递质释放最初减少，随后增加。当将GHB添加到脑切片中时观察到时间依赖性双相作用，在全身给予GHB后，透析液中出现剂量依赖性双相作用。纳洛酮在体外和体内均阻断GHB诱导的多巴胺积累和释放。GHB还增加了纹状体中阿片样物质的释放。GHB受体的特异性拮抗剂完全阻断了多巴胺反应和阿片样物质的释放。这些数据表明，GHB通过可能调节阿片中间神经元活性的特异性受体增加多巴胺释放。
