Howard S G, Feigenbaum J J
UCLA, Department of Molecular and Medical Pharmacology 90024, USA.
Biochem Pharmacol. 1997 Jan 10;53(1):103-10. doi: 10.1016/s0006-2952(96)00664-8.
gamma-Hydroxybutyrate (GHB) is generally considered to be an inhibitor of striatal dopamine (DA) release. However, a number of recent reports and at least one major review suggest that GHB enhances rather than inhibits striatal DA release. To examine this discrepancy, the effect of GHB on striatal DA release was monitored for 2 hr by microdialysis in awake and urethane-anesthetized rats. GHB (500 mg/kg, i.p.) significantly inhibited striatal DA release in conscious animals. However, anesthetic pretreatment completely abolished the inhibitory effect of GHB on DA release. In urethane-anesthetized animals, intraperitoneal injections of GHB resulted in a dialysis DA output that was the same as basal and saline control levels for all but the last three intervals where DA release was elevated slightly. In contrast to the intraperitoneal route, subcutaneous injections of GHB in anesthetized animals produced significant elevations of DA release above baseline levels. The increases ranged from 125 to 133% of basal levels. These results indicate that while GHB enhances striatal DA release in anesthetized animals, it inhibits rather than enhances this release in awake animals. This would explain why GHB induces an inhibition of DA-release-dependent behaviors rather than an enhancement. The results also indicate that the route of GHB administration influences its effects on striatal DA release, at least in anesthetized animals.
γ-羟基丁酸（GHB）通常被认为是纹状体多巴胺（DA）释放的抑制剂。然而，最近的一些报道以及至少一篇主要综述表明，GHB增强而非抑制纹状体DA释放。为了研究这种差异，通过微透析对清醒和氨基甲酸乙酯麻醉的大鼠纹状体DA释放进行了2小时监测。GHB（500mg/kg，腹腔注射）显著抑制清醒动物的纹状体DA释放。然而，麻醉预处理完全消除了GHB对DA释放的抑制作用。在氨基甲酸乙酯麻醉的动物中，腹腔注射GHB导致除最后三个时间段外所有时间段的透析DA输出与基础水平和生理盐水对照水平相同，在最后三个时间段DA释放略有升高。与腹腔注射途径相反，在麻醉动物中皮下注射GHB使DA释放显著高于基线水平。升高幅度为基础水平的125%至133%。这些结果表明，虽然GHB在麻醉动物中增强纹状体DA释放，但在清醒动物中它抑制而非增强这种释放。这可以解释为什么GHB诱导抑制DA释放依赖性行为而非增强。结果还表明，GHB的给药途径影响其对纹状体DA释放的作用，至少在麻醉动物中是这样。
