*3.1. Study Selection*

A total of 121 unique citations was initially retrieved through the combined search, after which 108 citations were excluded after full-text screening because they did not meet the inclusion criteria. Therefore, 13 studies (Pandolfo et al., 2013 [51]; Ouichi et al., 2013 [52]; Caballero et al., 2011 [53]; Ruiz-Oliveira et al., 2019 [54]; Higgins et al., 2007 [55]; França et al., 2020 [56]; Nunes et al., 2018 [57]; Szczepanik et al., 2016 [58]; Pires et al., 2010 [59]; Prediger et al., 2005 [60]; Leffa et al., 2019 [61]; Pires et al., 2009 [62]; Alves et al., 2020 [63]) on animal models were finally considered. Based on their methodology, the studies in this review could be classified as experimental (*n* = 10; 76.9%), randomly assigning the subjects sample to the experimental groups, and quasi-experimental (*n* = 3; 23.1%), where the groups were usually constructed according to the subject's characteristics. The first studies relevant to the topic were from 2005, while the most recent studies included in this review were published in 2020. Table 1 describes each article individually.

### 3.1.1. Species, Animal Model, Sex, and Treatment

Most of the animal studies were performed on rodents. Ten studies were conducted with rats and two with mice. Only one of the studies used zebrafish as an animal model. Four studies used only males, five used both males and females, and four used only females. Different caffeine treatments and routes of administration were used, along with different durations (Table 1). Chronic treatments were mainly performed by dilating caffeine powder

in the system water, whereas acute treatments were mainly administered intraperitoneally (i.p.).
