Shephard R A, Toal L, Leslie J C
Behavioural Analysis and Behavioural Biology Research Centre, University of Ulster, Jordanstown, Newtownabbey, N. Ireland, UK.
Pharmacol Biochem Behav. 1990 May;36(1):39-43. doi: 10.1016/0091-3057(90)90122-x.
Certain drugs generally regarded as GABA agonists, such as valproate and combinations of muscimol and baclofen, have been reported to produce apparent anxiolytic effects in various animal behavioral tests. The present paper reports two experiments on the effects of these agents on conditioned suppression in rats. In the first study, muscimol (0, 1.25 micrograms/kg or 1 mg/kg), baclofen (0, 1 mg/kg) and combinations of these treatments failed to alleviate conditioned suppression. Experiment Two showed that valproate (200 mg/kg) did attenuate conditioned suppression, and that its effects were antagonised by picrotoxin (1.5 mg/kg), but not by bicuculline (1.5 mg/kg), Ro 15-1788 (10 mg/kg) or by delta-amino-n-valeric acid (10 mg/kg). The findings are discussed in the context of the proposed GABA/benzodiazepine receptor complex, with the conclusion that there is little evidence for a mediating role of GABAa or GABAb receptors in such drug actions, and that the site of valproate action is probably the chloride ion channel associated with the receptor complex.
某些通常被视为GABA激动剂的药物，如丙戊酸盐以及蝇蕈醇与巴氯芬的组合，据报道在各种动物行为测试中会产生明显的抗焦虑作用。本文报告了两项关于这些药物对大鼠条件性抑制作用的实验。在第一项研究中，蝇蕈醇（0、1.25微克/千克或1毫克/千克）、巴氯芬（0、1毫克/千克）以及这些处理的组合未能减轻条件性抑制。实验二表明丙戊酸盐（200毫克/千克）确实减弱了条件性抑制，并且其作用被印防己毒素（1.5毫克/千克）拮抗，但不被荷包牡丹碱（1.5毫克/千克）、Ro 15 - 1788（10毫克/千克）或δ-氨基-n-戊酸（10毫克/千克）拮抗。这些发现结合所提出的GABA/苯二氮䓬受体复合物进行了讨论，得出的结论是，几乎没有证据表明GABAa或GABAb受体在此类药物作用中起介导作用，并且丙戊酸盐的作用位点可能是与受体复合物相关的氯离子通道。
