Adenosine has been widely recognized as an inhibitory modulator of the CNS.26 It acts as a homeostatic modulator at synapses26,27 and participates in neurotransmitter release,28 neuronal excitability, synaptic plasticity,29 and local inflammatory processes.30,31 Adenosine is complicated in neurobiology of learning and memory29,32,33 by overstimulating the N-methyl-d-aspartic acid (NMDA) receptors34,35 that influence long-term potentiation (LTP) and long-term depression (LTD).29 Additionally, adenosine participates in modulation of neurotransmissions exerted by dopamine (DA) and acetylcholine (Ach).36-48 Consumption of drugs of abuse and psychostimulants, either acutely or chronically, has shown to modify adenosine level in the brain.49 As such, a more clear understanding of the involvement of adenosine signaling pathway during addiction might help to explore potential treatments for substance use dependence.50 Several reports have indicated the involvement of adenosine in neuropathological conditions including stroke,51,52 epilepsy,53 PD,54-57 and other neurodegeneration disorders.31
