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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam.
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Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam.

机译：拮抗吡咯烷酮和咪达唑仑对小肠毒素引起的多巴胺和5-羟色胺代谢变化的拮抗作用。

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The effects of allopregnanolone and midazolam, given intracerebroventricularly, on the behavioral and biochemical effects of picrotoxin, were examined in a model of neurotoxin-induced seizures, in mice. After acute injections, midazolam (ED(50)=39.8 nmol) and allopregnanolone (ED(50)=11.0 nmol) produced similar and dose-dependent protection against picrotoxin-induced seizures. Picrotoxin given intraperitoneally at the ED(85) dose decreased significantly the concentration of serotonin (5-HT), dopamine (DA), homovanilic acid (HVA) and 3,4-dihydroxyindolacetic acid (DOPAC), in the mouse striatum and the frontal cortex, in the period of time immediately preceding the onset of seizures. A single injection of allopregnanolone more potently, in comparison to midazolam, antagonized the biochemical action of picrotoxin, abolishing its effects on DA, HVA and 5-HT concentration, in the mouse striatum and the frontal cortex. These results for the first time provide a direct argument for an involvement of central dopaminergic and serotonergic systems in the seizure development. The present data add also to the accumulating evidence suggesting a favorable pharmacological profile for some neurosteroids currently considered to have a future role in the management of epilepsy.
机译：在小鼠的神经毒素诱发的癫痫发作模型中，检查了脑室内给予的去甲萘普那诺酮和咪达唑仑对微毒素的行为和生化作用的影响。急性注射后，咪达唑仑（ED（50）= 39.8 nmol）和去甲泼奴那龙（ED（50）= 11.0 nmol）产生了类似的剂量依赖性保护作用，以抵抗微毒素诱导的癫痫发作。 ED（85）剂量腹膜内给予的微毒素可显着降低小鼠纹状体和额叶中5-羟色胺（5-HT），多巴胺（DA），高香草酸（HVA）和3,4-二羟基吲哚乙酸（DOPAC）的浓度癫痫发作前一段时间内的皮质。与咪达唑仑相比，单次注射Allopregnanolone更有效地拮抗了微毒素的生化作用，从而消除了其对小鼠纹状体和额叶皮层中DA，HVA和5-HT浓度的影响。这些结果首次为中央多巴胺能和血清素能系统参与癫痫发作提供了直接论据。本数据还增加了积累的证据，表明一些目前被认为在癫痫治疗中具有未来作用的神经固醇的药理学特征良好。

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