Promises of Caffeine in Attention-Deficit/Hyperactivity Disorder: From Animal Models to Clinical Practice

Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common chronic childhood-onset psychiatric disorders. ADHD persists in many cases into adulthood, the occurrence which is associated with attentional deficits, hyperactivity, and/or cognitive impulsiveness. A primary role of disturbances in frontocortical dopaminergic neurotransmission in ADHD is the basis for the current pharmacological treatment with psychostimulants, mainly methylphenidate. However, there is considerable evidence that nondopaminergic alterations, including alterations in adenosinergic neuromodulation, also occur in different brain areas. We now examine findings reported in clinical and animal studies to provide a comprehensive summary of the effects of caffeine, a nonselective adenosine receptor antagonist, in ADHD. Additionally, we investigate the effects of caffeine and physical exercise on emotional impairments observed in spontaneously hypertensive rats (SHRs), a validated animal model of ADHD. Methods: Male SHRs were submitted from adolescence (30 days old) to adulthood to the association of caffeine intake (0.3 mg/mL in drinking water) plus voluntary physical exercise in running wheels during 6 weeks. After that, depressive- and hedonic-like behaviors were evaluated in the forced swimming test (FST) and splash test. Findings: The clinical use of caffeine remains poorly investigated so far and the available results have been generally positive but somewhat inconsistent, which can be largely attributed to methodological concerns. In contrast, many studies have shown that caffeine treatment improved memory and attention deficits and also normalized dopaminergic function in adolescent and adult SHRs. In this study, we provide a comprehensive view of the effects of caffeine in ADHD and in SHRs, and we include new findings from our research group supporting the potential of caffeine and physical exercise in improving depressive-like behaviors of SHRs. Conclusion: Altogether, the evidence indicates that caffeine is a promising therapeutic tool to improve cognitive and emotional symptoms in ADHD. Thus, further controlled clinical studies are necessary with a careful adjustment of the doses of caffeine to adequately exploit this potential.