Adenosinergic system: an assorted approach to therapeutics for drug addiction

Abstract

Adenosine is an endogenous purine nucleoside and it is extensively present in the brain. It exerts several metabolic and neuromodulatory roles in the body. Adenosine also acts as an important messenger molecule for extracellular signaling and shows a homeostatic neuromodulatory function at the synaptic level. Extracellular adenosine exerts a wide variety of biological actions through four cell surface G-protein-coupled receptor subtypes, namely A1, A2A, A2B and A3 adenosine receptors. The extracellular levels of adenosine have been found to be enhanced in several neuropathological conditions, including drug addiction, and thus a neuroprotective role of adenosine was perceived by various experimental studies. The aversive withdrawal symptoms emanating from drug discontinuation provokes rebound drug intake patterns. In addition, alteration of neurotransmitter(s) release and changes in receptor expression contribute to the behavioral changes of drug withdrawal. Furthermore, the abuse of major drugs such as alcohol and opioids are reported to modulate extracellular adenosine levels. In this context, the neuromodulatory functions of adenosine would be valuable if projected to the clinical applications and thus, an increasing attention is currently given to the functional role of adenosine in human addictive disorders. This review will focus on recent clinical and experimental studies that reveal the actions of adenosine and related ligands in drug addiction and various drug-withdrawal syndromes. The evidence and reports provided in this review highlight the looming therapeutic potential of purinergic drugs, with a hope that new therapeutic interventions based on the adenosinergic concept will emerge in the coming years for the management of drug withdrawal syndrome.