Chronic caffeine treatment disrupts the circadian rhythm in Drosophila

The circadian clock governs the timing of sleep-wake cycles as well as of other behavioural, physiological and metabolic processes. While the endogenous circadian clock mediates the timing of sleep, homeostatic mechanisms modulate the amount and depth of sleep. Evidence from previous studies showed that caffeine intake promotes wakefulness, whereas adult-stage specific caffeine treatment not only suppresses sleep but also delays the phase of circadian rhythm in Drosophila. In humans, caffeine is consumed on a daily basis and hence it is important to understand the effect of prolonged caffeine intake on circadian and homeostatic regulation of sleep. In the present study we examined the differential effect of acute and chronic caffeine treatment on sleep ontogeny as well as on circadian and homeostatic regulation of sleep in Drosophila. The results of our study showed that acute caffeine treatment reduces day and night sleep in mature flies through the homeostatic pathway whereas it reduced only the day sleep in young flies. Chronic caffeine treatment did not exert any significant effect on sleep in young flies. On the other hand, it delayed the timing of sleep in mature flies and in addition flies under higher caffeine concentration reduced the morning and evening anticipatory activity under 12 hour: 12 hour light: dark cycles. These flies also exhibited either a longer free running period or arrhythmicity under constant darkness. The results of our study showed that acute caffeine treatment suppresses sleep through the homeostatic pathway whereas prolonged caffeine treatment disrupts the circadian rhythm in mature flies.

Chronic caffeine use does not influence behavior and brain oxidative status in mice

Amplamente consumida nos alimentos e como suplemento alimentar, a cafeína tem sido estudada devido aos seus efeitos farmacológicos, principalmente no sistema nervoso central (SNC). O presente estudo investigou se o uso crônico da cafeína pode influenciar o estado oxidativo do cérebro e a atividade comportamental de camundongos fêmeas C57BL/6. Para isso, quinze animais foram randomizados nos seguintes grupos: Controle (solução salina à 0,9%), Caf10 (10 mg / kg de cafeína) e Caf50 (50 mg / kg de cafeína). Os animais receberam uma dose diária de cafeína por via i.p. durante 120 dias. Vinte e quatro horas após a última administração, os animais foram submetidos a testes comportamentais e foram eutanasiados. O sangue foi utilizado para análises bioquímicas. No cérebro, foi avaliado o estado oxidativo e os níveis de microminerais. A cafeína não influenciou os parâmetros antropométricos, perfil lipídico e níveis de proteína Creativa. Ademais, as atividades de superóxido dismutase (SOD) e glutationa-Stransferase (GST) mantiveram o mesmo perfil de resposta. Em contrapartida, a atividade da catalase (CAT) diminuiu em ambos os grupos que receberam cafeína. Já os níveis de malondialdeído e proteína carbonilada não se alteraram entre os grupos, assim como a distribuição dos microminerais. Nenhuma dose de cafeína desencadeou comportamento do tipo ansioso nos animais. Portanto, considerando o tempo de administração da cafeína, acreditamos que houve a adaptação celular desencadeada pelo seu uso, tendendo a um efeito protetor no cérebro. Além disso, o espaço amostral reduzido foi uma limitação para entendimentos mais acurados sobre os efeitos da cafeína no SNC. Palavras-chave: Cafeína. Espécies reativas de oxigênio. Comportamento Animal.

Effect of Chronic Caffeine Administration on Expression Ratio of Bax and Bcl-2 Proteins in Myocardial Tissue of Male Wistar Rats With Type 2 Diabetes

Objective: Some previous studies have shown the protective effect of caffeine on apoptosis through the regulation of pro- and anti-apoptotic proteins. The aim of this study was to investigate the effects of chronic caffeine administration on the expression ratio of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-Associated X-protein (Bax) proteins in the cardiac tissue of rats with Type 2 Diabetes. Methods: In this experimental study, samples were 24 male white wistar rats (aged 2-3 months with a weight of 250-300 g) randomly divided into three groups: Healthy control (n=8), untreated diabetic (n=8), and diabetic with caffeine supplement (n=8; 70 mg/kg-1 for 8 weeks, 5 days a week). The expression of proteins associated with apoptotic signaling pathway (Bax and Bcl-2) in the cardiac muscle (left ventricular) was measured by Western blot method. One-Way Variance (ANOVA), t-test, and Tukey’s post hoc test were used for data analysis. Results: Induction of type two diabetes significantly increased the expression of Bax protein (1.81±0.2) and decreased the expression of Bcl-2 protein (0.36±0.05) compared to control group (P=0.001). However, caffeine administration increased the expression of Bax protein (131%) compared to diabetic control group (P=0.001). Therefore, caffeine administration after diabetes induction elevated the Bax/Bcl-2 ratio (P=0.001). Conclusion: Eight weeks of caffeine administration have an exacerbating effect on the apoptotic cell death caused by type 2 diabetes by increasing pro-apoptotic proteins and reducing anti-apoptotic proteins.

The Effect of Low-Doses of Caffeine and Taurine on Convulsive Seizure Parameters in Rats

Introduction: Caffeine, an adenosine-receptor blocker, is believed to have neuronal excitatory effects, while Taurine, a mammalian amino acid, was shown to have neuroinhibitory effects. Aim: The aim of this study was to investigate the effects of acute and chronic administration of low doses of Caffeine and Taurine on the seizure threshold in rats. Methods: Six-week-old Sprague-Dawley male rats (n = 280) were divided randomly into five groups (control, acute caffeine intake, acute taurine intake, chronic caffeine intake and chronic taurine intake), with five subgroups per group according to five different doses of Pentylenetetrazole (PTZ) injections. Each subgroup consisted of eight rats. Data was entered and analyzed using Microsoft EXCEL and AddinsoftTM XLSTAT (Version 2012.6.06; New York, NY, USA). p-value = 0.05 was regarded as statistically significant. Results: There was a significant decrease in the latency of PTZ-induced seizures with both acute (p-value < 0.05) and chronic (p-value < 0.01) Caffeine treatment groups. Chronic exposure to Caffeine exhibited an increase in the probability of seizures (p-value < 0.05). However, acute exposure to Caffeine did not show a significant impact on the probability of seizures. Neither acute nor chronic exposures to Taurine had an effect on the probability of seizures, nor on the latency of PTZ-induced seizures. Discussion: Our study found that acute as well as chronic exposure to low doses of Caffeine (50 and 80 mg/kg) reduces the threshold, and hence increases the likelihood for seizures since it favors a state of neuronal hyper excitability through blocking of all adenosine receptors. On the other hand, acute or chronic exposure to Taurine did not show a significant effect on the PTZ-induced seizures parameters.

Panic Disorder and Chronic Caffeine Use: A Case-control Study

Background: Acute administration of caffeine produces panic attacks in most Panic Disorder (PD) patients, but little is known about chronic caffeine use in these patients. Objective: To assess caffeine use in patients with PD and to ascertain if caffeine consumption is associated with sociodemographic or clinical features. Methods: 65 adults with PD and 66 healthy controls were included in the current study. Their caffeine intake within the previous week was quantified with a questionnaire and compared. Harmful caffeine use was defined as consumption above 400 mg/day of caffeine. We tested for correlations between caffeine intake, demographic and clinical features. Results: Patients consumed significantly more caffeine than controls (P < 0.001). 14% (N = 9) of the PD patients made harmful use of caffeine. The use of caffeine-containing medications was observed in 40% (N = 26) of the PD patients and 6% (N = 4) of controls. Consumption of energy drinks was observed in 11% (N = 7) of PD patients and in none of the healthy subjects. Patients reported sleeping significantly less than controls (P < 0.001). In PD patients, caffeine consumption was not correlated with the presence of panic attacks or comorbidity with depression. The use of benzodiazepines or sedative medications was not correlated with caffeine intake. Conclusion: High caffeine consumption in PD patients could be explained by the development of tolerance with regular use of this substance. Subtypes of sensitive and non-sensitive PD patients could also explain why some of these patients are able to tolerate high doses of caffeine.