Adenosine A2AR blockade increases the nicotine-induced [3H]DA release from rat striatal synaptosomes. (A) Time course and (B) bar graph displaying the averaged release of [3H]DA induced by nicotine alone or in the presence of the A2AR antagonist, ZM (100 nM). The co-administration of ZM and nicotine occurred as indicated by the horizontal bar in (A). (C) In a similar experimental paradigm, the non-selective adenosine receptor antagonist, caffeine (50 μM), failed to mimic the action of ZM, that is, to facilitate the effect of nicotine. (D) This lack of caffeine effect may be due to the involvement of A2BRs because the selective A2BR antagonist MRS (200 nM) inhibited the effect of nicotine and prevented the facilitatory action of ZM when the two antagonists were combined. Data are mean ± SEM of 6–13 experiments performed in duplicate. *P < 0.05 and ***P < 0.001 versus 0 FR% (i.e. no change in baseline); $P < 0.05 and $$P < 0.01 between the indicated bars in (B) and (C) and when compared to control (nicotine in the absence of any adenosine receptor antagonist, displayed with the leftmost bar) in (D); n.s., not significant.