Botton Paulo Henrique S, Pochmann Daniela, Rocha Andreia S, Nunes Fernanda, Almeida Amanda S, Marques Daniela M, Porciúncula Lisiane O
Laboratorio de Estudos sobre o Sistema Purinérgico, Departamento de Bioquimica/ICBS, Universidade Federal do Rio Grande do Sul; Rua Ramiro Barcelos, 2600 - anexo; Porto Alegre, RS 90035-003, Brazil.
Laboratorio de Estudos sobre o Sistema Purinérgico, Departamento de Bioquimica/ICBS, Universidade Federal do Rio Grande do Sul; Rua Ramiro Barcelos, 2600 - anexo; Porto Alegre, RS 90035-003, Brazil.
Physiol Behav. 2017 Mar 1;170:47-53. doi: 10.1016/j.physbeh.2016.11.030. Epub 2016 Nov 24.
Caffeine is the psychostimulant most consumed worldwide. Anxiogenic effects of caffeine have been described in adult animals with controversial findings about its anxiogenic potential. Besides, the effects of caffeine on anxiety with aging are still poorly known. In this study, adult mice (6months old) started to receive caffeine (0.3 and 1.0mg/mL, drinking water) during 12-14months only in the light cycle and at weekdays. The open field (OF) and elevated plus maze (EPM) testing were used to determine the effects of caffeine on anxiety-related behavior in adult and aged mice (18-20months old). Because aging alters synaptic proteins, we also evaluated SNAP-25 (as a nerve terminals marker), GFAP (as an astrocyte marker) and adenosine A and A receptors levels in the cortex. According to the OF analysis, caffeine did not change both hypolocomotion and anxiety with aging. However, aged mice showed less anxiety behavior in the EPM, but after receiving caffeine (0.3mg/mL) during adulthood they were anxious as adult mice. While SNAP-25 and adenosine A receptors increased with aging, both GFAP and adenosine A receptors were not affected. Caffeine at moderate dose prevented the age-related increase of the SNAP-25, with no effect on adenosine A receptors. The absence of effect for the highest dose suggests that tolerance to caffeine may have developed over time. Aged mice showed high responsiveness to the OF, being difficult to achieve any effect of caffeine. On the other hand this substance sustained the adult anxious behavior over time in a less stressful paradigm, and this effect was coincident with changes in the SNAP-25, suggesting the involvement of this synaptic protein in the ability of caffeine to preserve changes related to emotionality with aging.
咖啡因是全球消费最多的精神兴奋剂。咖啡因对成年动物的致焦虑作用已有描述，但其致焦虑潜力的研究结果存在争议。此外，咖啡因对衰老过程中焦虑的影响仍知之甚少。在本研究中，成年小鼠（6个月大）仅在光周期和平日期间，在12 - 14个月内开始饮用含咖啡因（0.3和1.0mg/mL）的水。采用旷场试验（OF）和高架十字迷宫试验（EPM）来确定咖啡因对成年和老年小鼠（18 - 20个月大）焦虑相关行为的影响。由于衰老会改变突触蛋白，我们还评估了皮质中SNAP - 25（作为神经末梢标志物）、GFAP（作为星形胶质细胞标志物）以及腺苷A和A受体的水平。根据旷场试验分析，咖啡因不会改变衰老过程中的运动减少和焦虑状态。然而，老年小鼠在高架十字迷宫试验中表现出较少的焦虑行为，但成年期饮用咖啡因（0.3mg/mL）后，它们变得和成年小鼠一样焦虑。虽然SNAP - 25和腺苷A受体随衰老增加，但GFAP和腺苷A受体均未受影响。中等剂量的咖啡因可阻止SNAP - 25随年龄增长而增加，对腺苷A受体无影响。高剂量无作用表明随着时间推移可能已产生对咖啡因的耐受性。老年小鼠对旷场试验反应性高，难以实现咖啡因的任何作用。另一方面，这种物质在压力较小的范式中随时间维持了成年小鼠的焦虑行为，且这种作用与SNAP - 25的变化一致，表明这种突触蛋白参与了咖啡因在衰老过程中保持与情绪相关变化的能力。
