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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >The effects of chronic administration of tranylcypromine and rimonabant on behaviour and protein expression in brain regions of the rat
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The effects of chronic administration of tranylcypromine and rimonabant on behaviour and protein expression in brain regions of the rat

机译：慢性酮丙氨酸慢性施用与乙二胺对大鼠脑区行为和蛋白表达的影响

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Recent findings indicate that CB1 receptor blockade might be relevant to the action of antidepressant drugs as inhibition of endocannabinoid function can increase synaptic availability of neurotransmitters; an effect also seen with chronic antidepressant drug treatment. Chronic treatments with established antidepressants also lead to raised brain BDNF levels. The aim of this study was to compare the effects of rimonabant (an inverse agonist/antagonist of CB1 receptors) with those of the antidepressant tranylcypromine (TCP), on behaviour and expression of BDNF/CREB signalling pathways in rat brain. Daily (i.p.) injections of vehicle or TCP (10 mg/kg) or rimonabant (2 mg/kg) were given for 14 days. Locomotor activity (LMA) and a conditional emotional response (CER) were measured in addition to levels of BDNF and CREB/phospho-CREB, using immunoblotting, in the frontal cortex, hippocampus, striatum and cerebellum. The velocity of movement was increased significantly on the 3rd, but not 9th, day of TCP treatment versus vehicle-treated rats (p < 0.05) while rimonabant had no effect. There were no significant changes in grooming or freezing behaviours after rimonabant or TCP compared to vehicle-treated rats. Rearing was significantly reduced by TCP treatment on the 3rd, but not 9th, day of treatment (p < 0.001) while rimonabant had no effect. BDNF levels were significantly increased in the frontal cortex after TCP (p < 0.05) but not by rimonabant. Neither TCP nor rimonabant significantly affected CREB or p-CREB expression. In conclusion, chronic administration of TCP to rats increased BDNF expression in the frontal cortex but no similar effect was observed with rimonabant indicating that rimonabant does not show antidepressant drug-like responses after chronic treatment.
机译：最近的发现表明，CB1受体阻滞可能与抗抑郁药物的作用相关，因为对内胆碱功能的抑制可以增加神经递质的突触可用性;用慢性抗抑郁药物治疗也看到了一种效果。具有已建立的抗抑郁药的慢性治疗也导致脑BDNF水平升高。本研究的目的是将乙二胺（CB1受体的反向激动剂/拮抗剂）与抗抑郁越桔（TCP）的影响进行比较，例如大鼠大脑中BDNF / CREB信号传导途径的行为和表达。每日（I.P.）注射载体或TCP（10mg / kg）或缩君子（2mg / kg）的注射14天。除了BDNF和CREB ​​/磷酸-CREB的水平，使用免疫印迹，在额叶，海马，纹状体和小脑中，还测量了运动活性（LMA）和条件情绪反应（CER）。运动速度显着增加，但第3个，但第9天，TCP治疗与载体处理的大鼠（P <0.05）没有影响，而乙月份没有效果。与载体处理的大鼠相比，剪枝系或TCP后的散装或冷冻行为没有显着变化。通过TCP处理在第3次的TCP处理显着降低，但第9天治疗（P <0.001），饲养饲养显着降低（P <0.001），而乙月份没有效果。在TCP后的前皮质中，BDNF水平显着增加（P <0.05）但不是rimonabant。 TCP也不是乙月份，影响CREB或P-CREB表达。结论总之，TCP对大鼠的慢性施用增加了前皮质中的BDNF表达，但用乙孢元体没有观察到类似的效果，表明乙二镰刀茎在慢性处理后未显示抗抑郁药物样反应。

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