Another important consideration in our study

Another important consideration in our study is the apparent decrease in locomotor activity and exploratory behavior observed in the rats after 48h of DOXO intraperitoneal treatment. The results of the present work demonstrated that DOXO reduced the crossing and rearing number in the open field test. A study performed by Liedke et al. [24] showed that animals treated with DOXO (0.5, 2 and 8mg/kg), evaluated in the open field 20min after DOXO, presented no differences in anxiety, locomotor activity and exploratory behavior. On the other hand, when the animals were tested 24h after DOXO treatment a reduced rearing number was observed, suggesting that DOXO can interfere with exploratory behavior. Several studies have previously shown that sleep alterations and sleep-deprived rats exhibit body weight loss and elevated corticosterone levels [25–27]. The immediate purpose of glucocorticoid release during stress situations is to provide readily usable Tariquidar manufacturer (i.e., glucose to the central nervous system). This release is accomplished together with catecholamines, GH and glucagon, to induce lipolysis, glycogenolysis, gluconeogenesis and, in cases of severe and prolonged stress, proteolysis [28]. These alterations can play an important role in the onset and maintenance of wasting found in the DOXO treatment. A study performed by Kaur et al. [29] showed that rats subjected to restraint stress demonstrated a reduction of locomotor and exploratory activity. Liu et al. [30] showed similar results in the chronic, unpredicted mild stress in rats. Moreover, stress is involved with the increase of corticosterone level as well reduction of locomotor activity and exploratory behavior in rats [31]. These results indicated that DOXO appears to induce a stress-like state. Recently, de Lima Junior [32] has showed that DOXO leads to conditions similar to cachexia, with severe glucose intolerance both in vivo and in vitro. We suggest that DOXO promotes less muscle mass, strength, and function, supporting the decrease in locomotor activity. However, this hypothesis is speculative and, therefore, further studies are needed. A point to note in the study was the dose of Doxo used in the procedure. This is not really used in clinical practice, however, this dose is currently used in several studies for analyzed of acute toxicity in the characterization of the molecular pathways in cardiotoxicity, sarcopenia and autophagy in skeletal muscle [33–35].
Conflict of Interest statement missing
Acknowledgments This work was supported by Grants from Associacão Fundo de Incentivo à Pesquisa (AFIP). Fabio Santos Lira thanks CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico) for their support (Universal, 481231/2012-9), and José Cesar Rosa Neto thanks Fapesp (Fundação de Amparo à Pesquisa do Estado de São Paulo) (13/09367-4).
Introduction Caffeine is a central nervous system stimulator that belongs to the class of molecules known as xanthines [1,2]. Caffeine is found in tea, coffee, mate, guarana paste and kola nuts, and it is consumed globally, irrespective of age or social status [3]. In humans, studies continue to shed light on the behavioural effects of caffeine [4,5], especially in adults; however, there is also a noticeable increase in the consumption of caffeine and caffeine-containing products by children and adolescents [6–9]. Studies have also been conducted to evaluate caffeine safety in the young [6,7], and to determine dose/consumer-dependent influences of caffeine use on the heart, blood-pressure and general body physiology in children [8,9]; however, in comparison to adults, data on caffeine research in the young is still less available. A major reason for deliberate caffeine consumption is to combat sleepiness. Sleepiness is defined as difficulty in maintaining alertness during the major wake period of the day, resulting in unintended lapses into drowsiness or sleep [10]. Sleepiness is a known consequence of sleep-deprivation in healthy humans; however, the quantity of sleep needed by children, adolescents and young adults is still debated [11,12]. Recent literature reveal that about 7–9h of sleep is adequate in young adults (18−25), 8–10h in teenagers and 9–11h in school aged children (6−13) [13]. It is also reported that sleep-deficits are higher in adolescents compared to other age-groups, with females showing greater need for sleep than males [14]. A number of human studies have reported no difference in total sleep time all through the adolescence period on non-school days, and significant loss of total sleep time only during school days [15,16], suggesting psychosocial factors as a sleep-time determinant in adolescents [17]. Sleep loss, and poor quality of sleep have been associated with alterations in emotional behaviour and decreased quality of life in young adults [18], and now studies are beginning to show evidence of increasing caffeine consumption in adolescents, to help cope with sleep loss [19]. Therefore, in this group, cycles of caffeine consumption and insufficient sleep tend to succeed each other.