Söderpalm B, Svensson L, Hulthe P, Johannessen K, Engel J A
Department of Pharmacology, University of Göteborg, Sweden.
Psychopharmacology (Berl). 1991;104(1):97-102. doi: 10.1007/BF02244561.
It is well known that benzodiazepines produce dependence in humans and locomotor stimulation in experimental animals. In this study the possible involvement of catecholamines in the diazepam-induced locomotor stimulation in mice were investigated. Diazepam was found to have a biphasic effect; increasing locomotor activity at a low dose (0.25 mg/kg), while decreasing it at higher doses (greater than 0.5 mg/kg). The locomotor stimulating effect of diazepam was effectively blocked by pretreatment with the benzodiazepine receptor antagonist flumazenil, as well as with the catecholamine synthesis inhibitor alpha-methyltryrosine and the dopamine receptor antagonists haloperidol, spiperone and SCH 23390. Taken together, these data indicate that the locomotor stimulating effect observed after low doses of diazepam is due to activation of brain dopaminergic systems involved in locomotor activity. The observations are discussed in relation to the hypothesis that dependence-producing drugs activate specific brain reward systems.
众所周知，苯二氮䓬类药物会使人产生依赖性，并在实验动物中引起运动兴奋。在本研究中，我们调查了儿茶酚胺在小鼠地西泮诱导的运动兴奋中可能发挥的作用。结果发现地西泮具有双相效应；低剂量（0.25mg/kg）时增加运动活性，而高剂量（大于0.5mg/kg）时降低运动活性。地西泮的运动兴奋作用可被苯二氮䓬受体拮抗剂氟马西尼、儿茶酚胺合成抑制剂α-甲基酪氨酸以及多巴胺受体拮抗剂氟哌啶醇、螺哌隆和SCH 23390预处理有效阻断。综上所述，这些数据表明低剂量地西泮后观察到的运动兴奋作用是由于参与运动活动的脑多巴胺能系统的激活。我们结合依赖性产生药物激活特定脑奖赏系统的假说对这些观察结果进行了讨论。
