Adenosine transiently modulates stimulated dopamine release in the caudate putamen via Al receptors

摘要

Adenosine modulates dopamine in the brain via A(1) and A(2A) receptors, but that modulation has only been characterized on a slow time scale. Recent studies have characterized a rapid signaling mode of adenosine that suggests a possible rapid modulatory role. Here, fast-scan cyclic voltammetry was used to characterize the extent to which transient adenosine changes modulate stimulated dopamine release (5 pulses at 60Hz) in rat caudate-putamen brain slices. Exogenous adenosine was applied and dopamine concentration monitored. Adenosine only modulated dopamine when it was applied 2 or 5s before stimulation. Longer time intervals and bath application of 5M adenosine did not decrease dopamine release. Mechanical stimulation of endogenous adenosine 2s before dopamine stimulation also decreased stimulated dopamine release by 417%, similar to the 54 +/- 6% decrease in dopamine after exogenous adenosine application. Dopamine inhibition by transient adenosine was recovered within 10min. The A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the dopamine modulation, whereas dopamine modulation was unaffected by the A(2A) receptor antagonist SCH 442416. Thus, transient adenosine changes can transiently modulate phasic dopamine release via A(1) receptors. These data demonstrate that adenosine has a rapid, but transient, modulatory role in the brain.