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首页> 外文期刊>The European Journal of Neuroscience >Repeated acetyl-l-carnitine administration increases phospho-Thr34 DARPP-32 levels and antagonizes cocaine-induced increase in Cdk5 and phospho-Thr75 DARPP-32 levels in rat striatum.
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Repeated acetyl-l-carnitine administration increases phospho-Thr34 DARPP-32 levels and antagonizes cocaine-induced increase in Cdk5 and phospho-Thr75 DARPP-32 levels in rat striatum.

机译:重复进行乙酰基-1-肉碱给药可增加大鼠纹状体中磷酸化-Thr34 DARPP-32的水平,并拮抗可卡因诱导的Cdk5和磷酸化-Thr75 DARPP-32的升高。

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Abstract Acute cocaine administration increases phosphorylation of dopamine and cAMP-regulated phosphoprotein (M(r) 32 kDa) (DARPP-32) at threonine (Thr)-34, whereas repeated cocaine administration increases DARPP-32 phosphorylation at Thr-75 in Sprague-Dawley rat striatum. Repeated acetyl-l-carnitine (ALCAR) administration persistently increases dopamine outflow in the nucleus accumbens. The present study examined the effect of repeated ALCAR administration on the DARPP-32 phosphorylation pattern in the nucleus accumbens and caudate-putamen. ALCAR increased phosphoThr-34 DARPP-32 levels and decreased phosphoThr-75 DARPP-32 levels, after 1 and 10 days of washout. We compared the effects of repeated cocaine and repeated ALCAR administrations on the behavioural response to cocaine challenge and on the DARPP-32 phosphorylation pattern and cyclin-dependent kinase 5 (Cdk5) levels in the striatum. We also studied whether ALCAR administered daily during or after cocaine sensitization procedure would interferewith the effects of cocaine. When the response to the cocaine challenge was assessed, cocaine- and ALCAR-treated rats showed a similar sensitized behavioural response, and rats receiving combined cocaine and ALCAR treatments, irrespective of treatment order, also showed a sensitized response. A week after the cocaine challenge, the two drugs had induced opposite modifications in DARPP-32 phosphorylation, as cocaine increased phosphorylation at Thr-75, while ALCAR increased phosphorylation at Thr-34. In cocaine plus ALCAR treated rats, irrespective of treatment order, ALCAR administration antagonized cocaine effects on DARPP-32 phosphorylation. Moreover, cocaine, but not ALCAR, increased DeltaFosB and Cdk5 expression, and the increase in Cdk5 was antagonized by ALCAR administration in rats receiving combined treatments. These effects were relatively persistent, as they were still present 7 days after the last treatment.
机译:摘要急性可卡因给药可增加苏氨酸(Thr)-34处多巴胺和cAMP调节的磷酸化蛋白(M(r)32 kDa)(DARPP-32)的磷酸化,而反复可卡因给药可增加Sprague-Shr-75中Thr-75处的DARPP-32磷酸化。道利大鼠纹状体。重复进行乙酰基-1-肉碱(ALCAR)给药会持续增加伏隔核中多巴胺的流出。本研究检查了重复ALCAR给药对伏伏核和尾状核的DARPP-32磷酸化模式的影响。冲洗1天和10天后,ALCAR增加了phosphoThr-34 DARPP-32的水平,并降低了phosphoThr-75 DARPP-32的水平。我们比较了重复可卡因和重复ALCAR给药对可卡因攻击的行为反应以及纹状体中DARPP-32磷酸化模式和细胞周期蛋白依赖性激酶5(Cdk5)水平的影响。我们还研究了在可卡因敏化手术期间或之后每天服用ALCAR是否会干扰可卡因的作用。当评估对可卡因激发的反应时,可卡因和ALCAR治疗的大鼠表现出相似的敏化行为反应,接受可卡因和ALCAR联合治疗的大鼠,不论治疗顺序如何,也表现出敏化反应。可卡因激发后一周,由于可卡因增加了Thr-75处的磷酸化,而ALCAR增加了Thr-34处的磷酸化,两种药物在DARPP-32磷酸化上诱导了相反的修饰。在可卡因加ALCAR治疗的大鼠中,不论治疗顺序如何,ALCAR给药均可拮抗可卡因对DARPP-32磷酸化的影响。此外,在接受联合治疗的大鼠中,可卡因而非ALCAR使DeltaFosB和Cdk5表达增加,而Cdk5的增加被ALCAR给药所拮抗。这些效果相对持久,因为它们在最后一次治疗后7天仍然存在。

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