Impact of Caffeine on Ethanol-Induced Stimulation and Sensitization: Changes in ERK and DARPP-32 Phosphorylation in Nucleus Accumbens
Impact of Caffeine on Ethanol-Induced Stimulation and Sensitization: Changes in ERK and DARPP-32 Phosphorylation in Nucleus Accumbens
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DOI：
10.1111/acer.14553
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发表时间：
2021-03-07
期刊：
影响因子：
--
通讯作者：
Correa，Merce
中科院分区：
文献类型：
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作者：
Porru，Simona;Lopez-Cruz，Laura;Correa，Merce
研究背景咖啡因常与乙醇一起摄入，以减轻乙醇引起的损害效应，包括精神活动迟缓或不协调。这两种药物都调节多巴胺（DA）相关的标记物在多巴胺（Acb），和Acb DA参与自主运动和运动敏化。本研究确定了咖啡因是否可以影响运动诱导的急性和反复乙醇给药在成年雄性CD-1 mice.MethodsAcute管理的咖啡因（7.5至30.0毫克/公斤）进行了评估，其影响急性乙醇诱导（1.5至3.5克/公斤）的变化，在开放领域的水平运动，支持的饲养，饲养不支持的墙壁。评估DA受体依赖性磷酸化标志物：细胞外信号调节激酶（pERK），以及Acb核心和外壳中苏氨酸75位点磷酸化的多巴胺和cAMP调节的磷蛋白Mr 32 kDa（pDARPP-32-Thr 75）。急性给药的咖啡因乙醇致敏（1.5 g/kg）mice.ResultsAcute乙醇降低两种类型的饲养也进行了评估。咖啡因增加支持直立，但不能阻止乙醇诱导的直立减少。这两种物质以双相方式增加水平运动，咖啡因增强乙醇诱导的运动。尽管乙醇反复给药可诱导运动和无支撑直立的致敏作用，但在无乙醇状态下向乙醇致敏小鼠急性给药咖啡因，与未使用乙醇的小鼠相比，刺激作用减弱。乙醇增加pERK免疫反应性在两个亚区的Acb，但与咖啡因共同管理钝化这种增加。有pDARPP-32（Thr 75）immunoreactivity.ConclusionsThe目前的结果表明，第一次给药后，咖啡因增强乙醇的刺激作用，但不抵消其抑制或共济失调的影响。此外，我们的研究结果表明，咖啡因在乙醇致敏动物中的激活作用较小。
BackgroundCaffeine is frequently consumed with ethanol to reduce the impairing effects induced by ethanol, including psychomotor slowing or incoordination. Both drugs modulate dopamine (DA)‐related markers in accumbens (Acb), and Acb DA is involved in voluntary locomotion and locomotor sensitization. The present study determined whether caffeine can affect locomotion induced by acute and repeated ethanol administration in adult male CD‐1 mice.MethodsAcute administration of caffeine (7.5 to 30.0 mg/kg) was evaluated for its effects on acute ethanol‐induced (1.5 to 3.5 g/kg) changes in open‐field horizontal locomotion, supported rearing, and rearing not supported by the wall. DA receptor‐dependent phosphorylation markers were assessed: extracellular signal‐regulated kinase (pERK), and dopamine‐and cAMP‐regulated phosphoprotein Mr32kDa phosphorylated at threonine 75 site (pDARPP‐32‐Thr75) in Acb core and shell. Acutely administered caffeine was also evaluated in ethanol‐sensitized (1.5 g/kg) mice.ResultsAcute ethanol decreased both types of rearing. Caffeine increased supported rearing but did not block ethanol ‐induced decreases in rearing. Both substances increased horizontal locomotion in a biphasic manner, and caffeine potentiated ethanol‐induced locomotion. Although ethanol administered repeatedly induced sensitization of locomotion and unsupported rearing, acute administration of caffeine to ethanol‐sensitized mice in an ethanol‐free state resulted in blunted stimulant effects compared with those seen in ethanol‐naïve mice. Ethanol increased pERK immunoreactivity in both subregions of the Acb, but coadministration with caffeine blunted this increase. There were no effects on pDARPP‐32(Thr75) immunoreactivity.ConclusionsThe present results demonstrated that, after the first administration, caffeine potentiated the stimulating actions of ethanol, but did not counteract its suppressant or ataxic effects. Moreover, our results show that caffeine has less activating effects in ethanol‐sensitized animals.