Nissbrandt H, Engberg G
Department of Pharmacology, Göteborg University, Sweden.
J Neural Transm (Vienna). 1996;103(11):1255-63. doi: 10.1007/BF01271186.
Previous studies have shown that administration of gamma-hydroxybutyric acid (GHBA) or baclofen is associated with a decrease in locomotor activity as well as an increase of dopamine (DA) in brain. In the present study we analyse whether these actions are related to activation of GABAB-receptors utilising a GABAB-receptor antagonist, CGP 35348. Administration of GHBA (200 or 800 mg/kg, i.p.) or baclofen (4 or 16 mg/kg, i.p.) induced a marked and dose-dependent decrease in locomotor activity in mice, that was antagonised by pretreatment with CGP 35348 (400 mg/kg, i.p.). Treatment with the highest doses of GHBA and baclofen produced clear-cut increases in forebrain DA concentration. Also these effects were effectively antagonised by pretreatment with CGP 35348. Treatment with the GABAB-receptor antagonist alone did not influence the locomotor activity or brain DA concentration. These results indicate that the behaviourally depressive and DA increasing effects of GHBA and baclofen are mediated by activation of GABAB-receptors.
以往的研究表明，给予γ-羟基丁酸（GHBA）或巴氯芬会导致运动活性降低以及脑内多巴胺（DA）水平升高。在本研究中，我们使用GABAB受体拮抗剂CGP 35348分析这些作用是否与GABAB受体的激活有关。给予GHBA（200或800mg/kg，腹腔注射）或巴氯芬（4或16mg/kg，腹腔注射）可使小鼠的运动活性显著降低且呈剂量依赖性，而预先给予CGP 35348（400mg/kg，腹腔注射）可拮抗这种作用。给予最高剂量的GHBA和巴氯芬可使前脑DA浓度明显升高。同样，这些作用也可被预先给予CGP 35348有效拮抗。单独给予GABAB受体拮抗剂对运动活性或脑内DA浓度没有影响。这些结果表明，GHBA和巴氯芬的行为抑制和DA升高作用是由GABAB受体的激活介导的。
