Adenosine fine tuning neuromodulation is a very subtle change, similar to what e.g., a pianist does, modulating a sound through insertion of another sound; so, modifying the characteristics of the previous sound. This is what adenosine does to modulate neurotransmitter actions. Adenosine neuromodulation is operated through high affinity inhibitory A1 and excitatory A2A receptors. These receptor...

There is mounting evidence that the neuropeptide oxytocin is a possible candidate for the treatment of drug addiction. Oxytocin was shown to reduce methamphetamine self-administration, conditioned place-preference, hyperactivity and reinstatement in rodents, highlighting its potential for the management of methamphetamine addiction. Thus, we hypothesised that the central endogenous oxytocinergi...

The synthesis of a new series of 2-(aryl)alkylthio derivatives of N-ethylcarboxamido adenosine (NECA) is described, in comparison with the corresponding derivatives of adenosine. Binding studies (A1, A2A, and A3) and adenylyl cyclase activity (A2B) at human adenosine receptor subtypes stably transfected in Chinese hamster ovary (CHO) cells showed that the 2(aryl)alkylthioadenosine derivatives a...

Zhan E, McIntosh VJ, Lasley RD. Adenosine A2A and A2B receptors are both required for adenosine A1 receptor-mediated cardioprotection. Am J Physiol Heart Circ Physiol 301: H1183–H1189, 2011. First published July 8, 2011; doi:10.1152/ajpheart.00264.2011.—All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be ex...

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease leading to motor neuron dysfunction resulting in impairment of neuromuscular transmission. A2A adenosine receptors have already been considered as a potential therapeutical target for ALS but their neuromodulatory role at the neuromuscular junction in ALS remains to be clarified. In the present work, we evaluated the effects of ...

Behavior is guided by motivation; such motivation includes effort and reward. The striatum plays a central role in integrating value of reward and effort associated with behavior, through converging inputs from multiple areas of the brain. Two antagonistic pathways within the striatum are involved in this process; the direct pathway which executes behavior that is rewarded and the indirect path...

In this opinion paper, we provide scientific-based reasons about the huge therapeutic potential of adenosine A2A receptor antagonists, and about the huge challenges to demonstrate efficacy in clinical trials, i.e., to provide data now required to approve a new medication by the regulatory bodies, such as U.S. Food and Drug Administration (FDA). Adenosine is an autacoid present in all tissue and...

Intraocular pressure is directly dependent on aqueous humor flow into, and resistance to flow out of, the eye. Adenosine has complex effects on intraocular pressure. Stimulation of A1 and A2A adenosine receptors changes intraocular pressure oppositely, likely through opposing actions on the outflow of aqueous humor. While the cellular sites regulating outflow resistance are unknown, the cells l...

Caffeine is the most widely used stimulant in Western countries. Some people voluntarily reduce caffeine consumption because it impairs the quality of their sleep. Studies in mice revealed that the disruption of sleep after caffeine is mediated by blockade of adenosine A2A receptors. Here we show in humans that (1) habitual caffeine consumption is associated with reduced sleep quality in self-r...

Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we inv...