Chronic Caffeine Administration Research Articles

Effectiveness of caffeine and blue-enriched light on cognitive performance and electroencephalography correlates of alertness in a spaceflight robotics simulation

Human cognitive impairment associated with sleep loss, circadian misalignment and work overload is a major concern in any high stress occupation but has potentially catastrophic consequences during spaceflight human robotic interactions. Two safe, wake-promoting countermeasures, caffeine and blue-enriched white light have been studied on Earth and are available on the International Space Station. We therefore conducted a randomized, placebo-controlled, cross-over trial examining the impact of regularly timed low-dose caffeine (0.3 mg per kg per h) and moderate illuminance blue-enriched white light (~90 lux, ~88 melEDI lux, 6300 K) as countermeasures, separately and combined, in a multi-night simulation of sleep-wake shifts experienced during spaceflight among 16 participants (7 F, ages 26–55). We find that chronic administration of low-dose caffeine improves subjective and objective correlates of alertness and performance during an overnight work schedule involving chronic sleep loss and circadian misalignment, although we also find that caffeine disrupts subsequent sleep. We further find that 90 lux of blue-enriched light moderately reduces electroencephalogram (EEG) power in the theta and delta regions, which are associated with sleepiness. These findings support the use of low-dose caffeine and potentially blue-enriched white light to enhance alertness and performance among astronauts and shiftworking populations.

Influence of a Nitric Oxide Synthase Inhibitor on the Anxiolytic, Stimulating, and Analgesic Effects of Long-Term Perinatal Caffeine Exposure in Rats.

We studied the effect of inducible NO synthase (iNOS) inhibitor aminoguanidine on the behavioral effects of chronic perinatal caffeine exposure. Administration of caffeine in the prenatal and early postnatal periods led to the development of anxiolytic, stimulating, and analgesic effects. Administration of aminoguanidine attenuated the anxiolytic and stimulating effects and potentiated the analgesic effect of perinatal administration of caffeine. Chronic perinatal administration of caffeine leads to significant changes in the level of anxiety, motor activity, and pain sensitivity, and inhibition of iNOS has a pronounced multidirectional effect on these effects.

Caffeine improves memory and cognition via modulating neural progenitor cell survival and decreasing oxidative stress in Alzheimer's rat model.

Caffeine possesses potent antioxidant, anti-inflammatory and anti-apoptotic activities against a variety of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). The goal of this study was to investigate the protective role of a psychoactive substance like caffeine on hippocampal neurogenesis and memory functions in streptozotocin (STZ)-induced neurodegeneration in rats. Caffeine is a natural CNS stimulant, belonging to the methylxanthine class, and is a widely consumed psychoactive substance. It is reported to abate the risk of various abnormalities that are cardiovascular system (CVS) related, cancer related, or due to metabolism dysregulation. Short-term caffeine exposure has been widely evaluated, but its chronic exposure is less explored and pursued. Several studies suggest a devastating role of caffeine in neurodegenerative disorders. However, the protective role of caffeine on neurodegeneration is still unclear. Here, we examined the effects of chronic caffeine administration on hippocampal neurogenesis in intracerebroventricular STZ injection induced memory dysfunction in rats. The chronic effect of caffeine on proliferation and neuronal fate determination of hippocampal neurons was evaluated by co-labeling of neurons by thymidine analogue BrdU that labels new born cells, DCX (a marker for immature neurons) and NeuN that labels mature neurons. STZ (1 mg/kg, 2 μl) was injected stereotaxically into the lateral ventricles (intracerebroventricular injection) once on day 1, followed by chronic treatment with caffeine (10 mg/kg, i.p) and donepezil (5 mg/kg, i.p.). Protective effect of caffeine on cognitive impairment and adult hippocampal neurogenesis was evaluated. Our findings show decreased oxidative stress burden and amyloid burden following caffeine administration in STZ lesioned SD rats. Further, double immunolabeling with bromodeoxyuridine+/doublecortin+ (BrdU+/DCX+) and bromodeoxyuridine+/ neuronal nuclei+ (BrdU+/NeuN+) has indicated that caffeine improved neuronal stem cell proliferation and long term survival in STZ lesioned rats. Our findings support the neurogenic potential of caffeine in STZ induced neurodegeneration.

Effects of chronic caffeine intake and withdrawal on neural activity assessed via resting-state functional magnetic resonance imaging in mice

Caffeine is a psychoactive substance that not only improves wakefulness, but also slows the cognitive decline caused by aging. However, at present, there are no reports about the effects of caffeine withdrawal, including headaches and changes in brain functional networks (nerve activity). Headache may occur approximately 24 h after discontinuing caffeine intake in chronic caffeine drinkers.The current study aimed to examine the brain functional activity via resting-state functional magnetic resonance imaging in chronically caffeinated and decaffeinated groups to investigate changes in brain activity caused by caffeine.C57BL/6J mice were included in the analysis, and they underwent 9.4-T ultrahigh-field magnetic resonance imaging. The mice were classified into the control, chronic caffeinated, and caffeine withdrawal grsoups. Mice were divided into three groups: 1) not exposed to caffeine (control); 2) treated with caffeine at a concentration of 0.3 mg/mL for 4 weeks (chronic caffeinated); and 3) treated as before with caffeine and withdrawn from caffeine for 24 h. After the three groups were examined, functional connectivity matrices were calculated using brain imaging analysis tools, and independent component analysis was performed.The results showed that caffeine administration activated neural activity areas in the stress response system. Furthermore, 24h after caffeine withdrawal, the results showed an increase in pain-related neural activity. In addition, caffeine administration was shown to activate the dentate gyrus, one of the hippocampal regions, and to decrease the neural activity in the olfactory bulb and anterior cingulate cortex.In the current research, the neural activity of specific brain regions changed after chronic caffeine administration and withdrawal.

Chronic caffeine ingestion improves memory and learning and increases neuronal population and dendritic length in the hippocampus of adult mice

Caffeine is the most widely consumed psychoactive drug in the world, ingested as natural components of chocolate, coffee and tea and as added components to soda and energy drinks. Here we assessed behavioural changes caused by chronic caffeine administration as well as morphological changes within specific regions of the adult mice brain: the hippocampus and amygdala. Twenty-four adult male albino mice were randomly divided into three groups. Caffeine was administered daily by gavage for 8 weeks at a dosage of 20 mg/kg for low dose (LD) group and 60 mg/kg for high dose (HD) group while the third group served as control (CNT). After the period of administration, neurobehavioural tasks were carried out; Morris water maze for learning and memory open field test and elevated plus maze test for anxiety. The mice were sacrificed; their brain tissues were harvested and processed for H&E, Cresyl violet and Golgi staining, and assessed qualitatively and quantitatively. Quantitative data from the neurobehavioural tests and neuronal cell counts were expressed as means ± standard errors of means and compared across the groups using analysis of variance (ANOVA). Significance was set at p< 0.05. Mice in the high dose group learnt faster and had significantly increased number of platform crossings in the Morris water maze test. There was, however, a slightly increased level of anxiety in the caffeine-treated mice, compared to controls. Histo-morphometric analysis revealed significantly increased number of pyramidal neurons in the hippocampus in the low dose group, but a decreased neuronal count in the amydala of the low dose and high dose groups compared to controls. The pyramidal neurons in the hippocampus of the caffeine-treated mice had increased apical dendritic length compared to the controls. Our findings strengthen the available data suggesting that prolonged caffeine intake improves cognition, and this process could be mediated by promoting the growth of dendrites and increased number of neurons. However, this is coupled with an increased tendency to be anxiogenic.

Chronic administration of caffeine alters acesulfame-K intake and features of fungiform taste buds in mice

The objective of this study was to investigate the effects of chronic administration of caffeine on the anatomical characteristics of taste buds, the expression level of taste receptor protein in mice, and preference for a palatable solution. We found that following a 21-day administration of caffeine, mice showed increased behavioural responses to sweet stimuli (acesulfame-K solution). Mirroring this behavioural change, chronic caffeine treatment evidently decreased the maximal cross-sectional area and height of the longitudinal axis of fungiform taste buds, the number of taste cells per fungiform taste bud, and the expression of G protein α-gustducin, while the expression of the sweet taste receptors T1R2 and T1R3 was reversed. Our findings demonstrate that chronic administration of caffeine has an impact on taste sensitivity and changes in taste bud features, which may contribute to the alteration of taste behaviour.

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.

Chronic and Acute Oral Administration of Caffeine Enhance Performance of Olfactory Learning in Crickets

Crickets were arbitrarily fed a caffeine-containing diet during their lifetime or were orally administered caffeine in solution once during the conditioning session. These chronically or acutely treated crickets were used to test whether there were positive effects of caffeine on their learning performance. The effects of chronic exposure to caffeine on crickets' growth were also examined by measuring their body weight and counting the number of adults that emerged from larvae. Chronic treatment with relatively high concentrations of caffeine (5 mg/g and 0.5 mg/g in the diet) impaired the growth of crickets. Mortality was higher with 5 mg/g caffeine, and the survivors could not attain the final molt (eclosion). Body weight gain and eclosion rate were also negatively influenced in the group fed 0.5 mg/g caffeine. The olfactory learning paradigm was used to examine the effects of chronic caffeine treatment. Of the caffeine concentrations tested (0.5 µg/g to 0.5 mg/g), significant improvement in long-term memory (LTM) formation was observed only with 50 µg/g caffeine. Acute effects on olfactory learning were examined after oral administration of 0.1 nM to 10 µM caffeine solutions during the conditioning session. Administration of caffeine ≥ 1 nM consistently resulted in a significant improvement in LTM formation. These results suggest that chronic exposure to caffeine enhances learning performance in crickets at a specific dose (50 µg/g in the diet), although it inhibits their growth at higher doses (≥ 0.5 mg/g). In contrast, acute oral administration of caffeine in naive crickets may enhance their learning performance even at a very low (nanomolar) concentration.

Effects of Chronic Caffeine Administration on Behavioral and Molecular Adaptations to Sensory Contact Model Induced Stress in Adolescent Male Mice.

Previous studies have shown that caffeine attenuates stress-induced mood dysfunction and memory deterioration through neuronal adenosine A2A receptors antagonism. However, whether caffeine exerts this effect through modulating other molecular targets, which interfere with the resilience to social defeat stress in adolescent male mice is unknown. This study was conducted to investigate the role of caffeine in the behavioral responses to social stress induced by the sensory contact model (SCM) and the possible alteration of the gene expression level of Na/K ATPase pump. Adolescent male mice were exposed to SCM for 12 days. Caffeine was administered intraperitoneal daily for 14 days after SCM. The time spent in interaction zone, social interaction ratio, preference index to novel objects, time spent in the open arms and immobility time in forced swimming test were used to measure the locomotor activity, social avoidance, short-term memory, anxiety and depression in mice. The results showed that chronic treatment with caffeine for 14 days improved locomotor activity, reversed the avoidance of social behavior, improved preference to novel objects, and reversed depression induced by social defeat stress in adolescent male mice, suggesting the enhancement of the resilience to social defeat stress induced by caffeine. Moreover, caffeine treatment did alter gene expression levels of Na/K ATPase isoforms in both prefrontal cortex and hippocampus. Altered gene expression was significant in most cases and correlates with the observed behavioral changes. Taken together, our findings provide new insight into the effects of chronic caffeine administration on locomotor activity, social avoidance, short-term memory and depression in adolescent male mice exposed to SCM.

Trait specific modulatory effects of caffeine exposure on compulsive-like behaviors in a spontaneous mouse model of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by recurring intrusive thoughts and repetitive compulsive behaviors, ultimately interfering with their quality of life. The complex heterogeneity of symptom dimensions across OCD patient subgroups impedes diagnosis and treatment. The core and comorbid symptomologies of OCD are thought to be modulated by common environmental exposures such as consumption of the psychostimulant caffeine. The effect of caffeine on the expression of obsessions and compulsions are unexplored. The current study utilized mouse strains (HA) with a spontaneous, predictable, and stable compulsive-like phenotype that have face, predictive, and construct validity for OCD. We demonstrate that an acute high dose (25 mg/kg) of caffeine decreased compulsive-like nest-building behavior in the HA strains in the first hour after injection. However, nest-building scores increased in hours 3, 4, and 5 after administration finally decreasing over a 24 h period. In contrast, a high dose of chronic caffeine (25 mg/kg/d) increased nest-building behavior. Interestingly for compulsive-like digging behavior, acute exposure to a high dose of caffeine decreased the number of marbles buried, while chronic exposure had little effect. An acute high dose of caffeine decreased anxiety-like and motor activity in open field behaviors whereas chronic caffeine administration did not have any overall effect on open field activity. The results, therefore, suggest a complex role of caffeine on compulsive-like, anxiety-like, and locomotor behaviors that is dependent on the duration of exposure.

Effects of chronic caffeine exposure during adolescence and subsequent acute caffeine challenge during adulthood on rat brain serotonergic systems

Caffeine is the most commonly used drug in the world. However, animal studies suggest that chronic consumption of caffeine during adolescence can result in enhanced anxiety-like behavioral responses during adulthood. One mechanism through which chronic caffeine administration may influence subsequent anxiety-like responses is through actions on brainstem serotonergic systems. In order to explore potential effects of chronic caffeine consumption on brainstem serotonergic systems, we evaluated the effects of a 28-day exposure to chronic caffeine (0.3 g/L; postnatal day 28–56) or vehicle administration in the drinking water, followed by 24 h caffeine withdrawal, and subsequent challenge with caffeine (30 mg/kg; s.c.) or vehicle in adolescent male rats. In Experiment 1, acute caffeine challenge induced a widespread activation of serotonergic neurons throughout the dorsal raphe nucleus (DR); this effect was attenuated in rats that had been exposed to chronic caffeine consumption. In Experiment 2, acute caffeine administration profoundly decreased tph2 and slc22a3 mRNA expression throughout the DR, with no effects on htr1a or slc6a4 mRNA expression. Chronic caffeine exposure for four weeks during adolescence was sufficient to decrease tph2 mRNA expression in the DR measured 28 h after caffeine withdrawal. Chronic caffeine administration during adolescence did not impact the ability of acute caffeine to decrease tph2 or slc22a3 mRNA expression. Together, these data suggest that both chronic caffeine administration during adolescence and acute caffeine challenge during adulthood are important determinants of serotonergic function and serotonergic gene expression, effects that may contribute to chronic effects of caffeine on anxiety-like responses.

Chronic treatment with caffeine and its withdrawal modify the antidepressant-like activity of selective serotonin reuptake inhibitors in the forced swim and tail suspension tests in mice. Effects on Comt, Slc6a15 and Adora1 gene expression

Recent preclinical and clinical data suggest that low dose of caffeine enhances the effects of common antidepressants. Here we investigated the effects of chronic administration of caffeine (5mg/kg, twice daily for 14days) and its withdrawal on day 15th on the activity of per se ineffective doses of fluoxetine (5mg/kg) and escitalopram (2mg/kg) given on day 15th. We found decreased immobility time in the forced swim and tail suspension tests in mice in which caffeine was administered simultaneously with antidepressants on day 15th following a 14-day caffeine treatment and no alterations in the spontaneous locomotor activity. A decrease in the level of escitalopram and an increase in the level of caffeine in serum were observed after concomitant administration of these compounds, while the joint administration of caffeine and fluoxetine was not associated with changes in their levels in serum or brain. Caffeine withdrawal caused a decrease in Adora1 mRNA level in the cerebral cortex (Cx). Administration of escitalopram or fluoxetine followed by caffeine withdrawal caused an increase in this gene expression, whereas administration of escitalopram, but not fluoxetine, on day 15th together with caffeine caused a decrease in Adora1 mRNA level in the Cx. Furthermore, antidepressant-like activity observed after joint administration of the tested drugs with caffeine was associated with decreased Slc6a15 mRNA level in the Cx. The results show that withdrawal of caffeine after its chronic intake may change activity of antidepressants with concomitant alterations within monoamine, adenosine and glutamate systems.

ARE THE SIDE EFFECTS OF PARACETAMOL BOOSTED BY CAFFEINE??

Paracetamol (acetaminophen) with caffeine is a combination medicine indicated for the temporary relief of pain and discomfort associated with a number of conditions such as headache or muscle pain. Paracetamol has a narrow safety margin and there are number of risks associated with paracetamol. It is only safe and effective when used according to directions on OTC (Over- The-Counter) and Rx labelling. However, long-term use of paracetamol increases the risk of kidney and liver failure and makes people more vulnerable to high blood pressure and strokes. Chronic or excessive administration of caffeine has been implicated in a range of dysfunctions involving the liver, renal system, gastrointestinal system, and musculature. A patient taking the combination of paracetamol with caffeine may be more likely to experience adverse effects than to get improved analgesia, compared with paracetamol alone. Keywords : Paracetamol, Caffeine, OTC, Hepatic Toxicity

The Role of Combined Nicotine and Caffeine Administration on the Histological Structure of the Rat Urinary Bladder with a Special Reference to P53

Background: It is difficult to find microscopic studies that can demonstrate the effect of combined administration of nicotine and caffeine on the mucosa of the rat urinary bladder. Aim of work: So, the current study aimed at demonstration of histological and p53 immuno-histochemical expression of the mucosa of rat urinary bladder as a marker sharing in process of apoptosis following the combined administration of nicotine and caffeine. Materials and methods: The animals were divided randomly into 4 groups: control, Nicotine, caffeine and combined Nicotine and Caffeine. The urinary bladder was processed and stained with hematoxylin and eosin stain, histochemically by PAS and immunohistochemically by Anti p53 antibodies. Results: After nicotine there was apparent increase in the layers of epithelium with intraepithelial lymphocytes. The strong PAS positive reaction of the basal layer together with P53 positive expression of few lamina propria cells was evident. After caffeine, the epithelial layers and mononuclear cells of the lamina propria were increased. There was a marked decrease in the PAS positive reacting cells of the superficial cell layer. The groups that have administered combine caffeine and nicotine; there were focal areas of epithelial erosion with proliferating basal layers. There was a strong PAS positive reaction under the basal layer and p53 positive expression of many lamina propria cells. Conclusion: The present study had concluded that the chronic administration of combined nicotine and caffeine could result in epithelial hyperplasia associated with positive P53 expression in nuclei of lamina propria cells of the urinary bladder mucosa.

Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling.

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC.

Caffeine increases food intake while reducing anxiety-related behaviors

The objective of this study was to determine the effects of different doses of caffeine on appetite and anxiety-related behavior. Additionally, we sought to determine if withdrawal from chronic caffeine administration promotes anxiety. In this study, we utilized rodent open field testing and feeding behavior assays to determine the effects of caffeine on feeding and anxiety-related behavior (n = 8 mice; 4–8 weeks old). We also measured 2 h and 24 h food intake and body-weight during daily administration of caffeine (n = 12 mice; 4–8 weeks old). To test for caffeine withdrawal induced anxiety, anxiety-related behavior in rodents was quantified following withdrawal from four consecutive days of caffeine administration (n = 12 mice; 4–8 weeks old). We find that acute caffeine administration increases food intake in a dose-dependent manner with lower doses of caffeine more significantly increasing food intake than higher doses. Acute caffeine administration also reduced anxiety-related behaviors in mice without significantly altering locomotor activity. However, we did not observe any differences in 24 h food intake or body weight following chronic caffeine administration and there were no observable differences in anxiety-related behaviors during caffeine withdrawal. In conclusion, we find that caffeine can both increase appetite and decrease anxiety-related behaviors in a dose dependent fashion. Given the complex relationship between appetite and anxiety, the present study provides additional insights into potential caffeine-based pharmacological mechanisms governing appetite and anxiety disorders, such as bulimia nervosa.

CHRONIC CAFFEINE'S EFFECTS ON BEHAVIOURAL CHANGES IN STREPTOZOTOCIN-INDUCED DIABETIC RATS.

Memory deficits, anxiety and depression are often associated with diabetes, worsening diabetic patients' prognosis. Caffeine, a worldwide used psychoactive substance, is a candidate for improving these conditions. The aim of this study was to assess the behaviour in streptozotocin-induced diabetic Wistar rats and to evaluate the behavioural effects of caffeine administration. Diabetes was induced by a single intraperitoneal injection of 50 mg/kg BW streptozotocin (n=10), while control rats received the vehicle (n=9). After six weeks, behavioural tests for anxiety, memory and depression were performed: elevated plus maze (EPM) test, novel object recognition (NOR) test and forced swimming test (FST), respectively. The tests were repeated after further 2 weeks of continuous caffeine administration (20 mg/kg BW/day in drinking water). Diabetic rats manifested a high anxiety level, showed by a reduced exploratory activity compared to control rats (p<0.05) and long-term memory impairment, spending more time near the old object in NOR test. Caffeine administered for 2 weeks did not modify glycemic values in either group, and attenuated the behavioural changes observed in the EPM test. Also, in NOR test for long-term memory, caffeine administration induced an increased time spent with the novel object than with the old one in both groups. Our data suggest that chronic caffeine administration has an anxiolytic effect in diabetic rats and improves long-term memory in both diabetic and control rats.

Effects of chronic caffeine administration at two different times of the day on sleep in rat

Effects of chronic caffeine administration at two different times of the day on sleep in rat

Chronic caffeine exposure attenuates blast-induced memory deficit in mice

ObjectiveTo investigate the effects of three different ways of chronic caffeine administration on blast-induced memory dysfunction and to explore the underlying mechanisms. MethodsAdult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR. ResultsAll of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption. ConclusionSince caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

Bicuculline Enhances Basal Ventilation in 12 Day‐Old Rats Chronically Treated with Caffeine.

Caffeine is the 1st line pharmacological treatment for apnea of prematurity and can be administered for days to weeks. Because of the close interaction between adenosine and GABA on respiratory control in newborn subjects, we tested here the hypothesis that chronic inhibition of adenosine receptors by daily caffeine administration modulates GABAa receptors function. In 12-day-old rats that were daily gavaged with water (control) or caffeine (15mg/kg) from postnatal day 3-12, we measured respiratory frequency, tidal volume, minute ventilation and metabolism (oxygen consumption and CO2 production) in normoxia while rats were awake and un-anesthetized (plethysmography). These measurements were performed following a single i.p. injection of vehicle (DMSO) or bicuculline (2mg/kg, specific GABAa receptor antagonist). In control rats, basal ventilation was not different between vehicle and bicuculline. In caffeine rats, bicuculline increased basal ventilation (+50%) compared to vehicle. No changes in metabolism were observed in control or caffeine rats. These results show that chronic caffeine administration induces important changes in GABAa receptor response that may be related to an increase in receptor density and/or in their sensitivity to GABA. Funded by CIHR (MOP 119272).