Caffeine effect on locomotor activity in the mammalian spinal cord
Caffeine is a potent psychostimulant that can have significant and widely variable effects on the activity of multiple neuronal pathways. The most pronounced caffeine-induced behavioral effect seen in rodents is to increase locomotor activity which has been linked to a dose-dependent inhibition of A1 and A2A receptors. The effects of caffeine at the level of the lumbar spinal central pattern generator (CPG) network for hindlimb locomotion are lacking. We assessed the effects of caffeine to the locomotor function of the spinal CPG network via extracellular ventral root recordings using the isolated neonatal mouse spinal cord preparation. Addition of caffeine and of an A1 receptor antagonist significantly decreased the cycle period accelerating the ongoing locomotor rhythm, while decreasing burst duration reversibly in most preparations suggesting the role of A1 receptors as the primary target of caffeine. Caffeine and an A1 receptor antagonist failed to stimulate ongoing locomotor activity in the absence of dopamine or in the presence of a D1 receptor antagonist supporting A1/D1 receptor-dependent mechanism of action. The use of caffeine or an A1 receptor blocker failed to stimulate an ongoing locomotor rhythm in the presence of a blocker of the cAMP-dependent protein kinase (PKA) supporting the need of this intracellular pathway for the modulatory effects of caffeine to occur. These results support a stimulant effect of caffeine on the lumbar spinal network controlling hindlimb locomotion through the inhibition of A1 receptors and subsequent activation of D1 receptors via a PKA-dependent intracellular mechanism.
Anatomical, biochemical, pharmacological and physiological characterization of functional adenosine A1-dopamine D1 receptor heteromers in mammalian spinal motoneurons
Adenosine is an ubiquitous neuromodulator in the central nervous system (CNS), which is involved in numerous functions. More general functions include the regulation of arousal and its role in neuroprotection. The modulatory role of adenosine on dopaminergic transmission depends largely on the existence of antagonistic interactions mediated by specific subtypes of adenosine and dopamine receptors, the so-called A2AR-dopamine D2 receptor (D2R) and A1R-dopamine D1 receptor (D1R) interactions. These specific adenosine-dopamine receptor interactions seem to be involved in the central effects of caffeine, a non-selective A1R-A2AR competitive antagonist. We have recently found a significant antagonistic interaction between A1R and D1R ligands in the mouse spinal cord that mediates the ability of caffeine to produce locomotor enhancement by acting on spinal circuits, although the molecular mechanisms and cellular localization remained to be determined. We used lumbar slices of the mouse spinal cord to conduct electrophysiological, immunohistochemical and biochemical techniques to detect the presence of A1R-D1R heteromers. In the present study, A1R-D1R heteromerization is first demonstrated in mammalian transfected cells using biophysical techniques. Synthetic peptides with the amino acid sequence of specific transmembrane domains (TMs) of the D1R provided the tool to demonstrate that the antagonistic interaction between A1R and D1R ligands depends on A1R-D1R heteromerization and allowed the specific identification of A1R-D1R heteromers in spinal motoneuron, where they mediate the spinal modulatory control by adenosine and dopamine and the strong spinal pharmacological effects of caffeine.
A Study of Energy Drink Consumption Patterns Among College Students
Caffeine is the most consumed psychoactive substance in the world. It is considered a stimulant drug that can have significant and widely variable effects on the activity of neuronal pathways in the central and peripheral nervous system including the modulation of behaviors such as vigilance, attention, arousal, and locomotor activity. It is also the most common stimulant in the so called “energy beverages” (EB) which are being recently used at an alarming frequency by people looking to extend “peak” activity during working hours or even by athletes seeking a “boost” in performance at endurance events. Since its introduction in 1996 to the US market, energy drink consumption has continued to gain immense popularity especially between adults 18-35 years old. Recent studies in the United States have shown that the consumption of energy drinks among college students has increased dramatically within the last 7-8 years including actual percentage of students consuming these caffeine-containing beverages on a regular basis to be above 50 percent. The purpose of our study was to determine energy drink consumption patterns among students at the University of Puerto-Rio Piedras campus which contains the largest and most diverse student body in Puerto Rico. We wanted to assess the prevalence and frequency of energy drink use among specific situations which included: studying, sporting events, social gatherings, during family related events…among others. Additionally, we assessed the patterns, prevalence and frequency of consumption of energy drinks mixed with alcoholic beverages. Responses were acquired through a 24-item online confidential questionnaire which gathered basic demographic information and acquired data regarding consumption patterns of energy drinks as described above. Future research should identify if college students recognize the amounts of caffeine that are present in the wide variety of caffeine-containing products that they are consuming, the amounts of caffeine that they are consuming in various situations, and the physical side effects associated with caffeine consumption.