Attention deficit hyperactivity disorder (ADHD) is a prevalent and disabling disorder, mainly characterized by hyperactivity, inattention, and impulsivity, but also by olfactory and memory impairments that frequently persist throughout lifetime. The pathophysiology of ADHD is complex, involving several brain regions and neural pathways including alterations in adenosine neuromodulation. The administration of caffeine (a non-selective adenosine receptor antagonist) and physical exercise have been independently pointed as effective approaches for the management of ADHD symptoms. Here, we evaluated the effects of caffeine consumption (0.3 mg/mL in drinking water) plus physical exercise in running wheels during 6 weeks—starting during either adolescence (30 days old) or adulthood (4–5 months old)—on behavioral performance (including olfactory discrimination, open field, object recognition, and water maze tests) on the brain levels of monoamines (by high-performance liquid chromatography), on proteins related to synaptic plasticity and on brain-derived neurotrophic factor signaling (by Western blot analysis) in spontaneously hypertensive rats (SHRs), a validated animal model of ADHD. SHRs displayed persistent impairments of olfactory and short-term recognition memory from adolescence to adulthood, which were accompanied by lower levels of synaptosomal-associated protein 25 (SNAP-25) in the prefrontal cortex and hippocampus. The association of caffeine plus physical exercise during adolescence or adulthood restored the olfactory discrimination ability and, in an independent manner, improved short-term recognition memory of SHRs. These benefits were not associated to alterations in locomotor activity or in the hypertensive phenotype. The association of caffeine consumption plus physical exercise during adolescence increased the levels of SNAP-25, syntaxin, and serotonin in the hippocampus and prefrontal cortex, and striatal dopamine levels in SHRs. These results provide new evidence of the potential of caffeine and physical exercise, starting at adolescence or adult life, to improve behavioral impairments and stimulate neuroplasticity in ADHD.

注意缺陷多动障碍（ADHD）是一种普遍存在的致残性疾病，其主要特征是活动过度，注意力不集中和冲动，但特征还在于嗅觉和记忆障碍，终生持续存在。ADHD的病理生理学很复杂，涉及多个脑区域和神经通路，包括腺苷神经调节的改变。咖啡因（一种非选择性的腺苷受体拮抗剂）和体育锻炼已被独立地指出是治疗多动症的有效方法。在这里，我们评估了咖啡因消耗的影响（0。在饮用水中添加3 mg / mL），并在6周内在运行轮上进行体育锻炼-从青春期（30天大）或成年（4-5个月大）开始-行为表现（包括嗅觉辨别，视野开阔，物体识别）自发性高血压大鼠（SHRs）的脑中单胺水平（通过高效液相色谱法），与突触可塑性相关的蛋白和脑源性神经营养因子信号传导（通过Western印迹分析）经过验证的多动症动物模型。SHRs表现出从青春期到成年期的嗅觉和短期识别记忆的持续损害，并伴随着额叶前额叶皮层和海马中突触体相关蛋白25（SNAP-25）的降低。咖啡因与体育锻炼的结合在青春期或成年期恢复了嗅觉辨别能力，并以独立的方式改善了SHR的短期识别记忆。这些益处与运动活性或高血压表型的改变无关。青春期期间摄入咖啡因与体育锻炼的相关性增加了海马和前额叶皮层中SNAP-25，语法和血清素的水平，以及SHRs的纹状体多巴胺水平。这些结果提供了咖啡因和体育锻炼从青春期或成年期开始，以改善行为障碍和刺激多动症神经可塑性的潜力的新证据。改善了SHR的短期识别记忆。这些益处与运动活性或高血压表型的改变无关。青春期期间摄入咖啡因与体育锻炼的相关性增加了海马和前额叶皮层中SNAP-25，语法和血清素的水平，以及SHRs的纹状体多巴胺水平。这些结果提供了咖啡因和体育锻炼从青春期或成年期开始，以改善行为障碍和刺激多动症神经可塑性的潜力的新证据。改善了SHR的短期识别记忆。这些益处与运动活性或高血压表型的改变无关。青春期期间摄入咖啡因与体育锻炼的相关性增加了海马和前额叶皮层中SNAP-25，语法和血清素的水平，以及SHRs的纹状体多巴胺水平。这些结果提供了咖啡因和体育锻炼从青春期或成年期开始，以改善行为障碍和刺激多动症神经可塑性的潜力的新证据。以及海马和前额叶皮层的5-羟色胺和SHRs的纹状体多巴胺水平。这些结果提供了咖啡因和体育锻炼从青春期或成年期开始，以改善行为障碍和刺激多动症神经可塑性的潜力的新证据。海马和前额叶皮质中的血清素，SHR中的纹状体多巴胺水平。这些结果提供了咖啡因和体育锻炼从青春期或成年期开始，以改善行为障碍和刺激多动症神经可塑性的潜力的新证据。