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Background Objective Methods Results Conclusion Adenosinergic system has been implicated in the pathophysiology of bipolar disorder and drugs that affect adenosine neurotransmission have shown some efficacy as add‐on therapy in manic patients.Thus, the aim of the present study was to screen adenosinergic drugs for antimanic‐like effect in methylphenidate (MPH)‐induced hyperlocomotion in mice.Male and female Swiss mice received a single allopurinol (50 and 200 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) administration before an acute MPH challenge (5 mg/kg, sc). In experiments with repeated treatment, male mice received a daily administration of allopurinol (25 and 50 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) for 14 days. Finally, pretreatment with aminophylline (2 mg/kg, sc), an unspecific adenosine receptor antagonist, was used to evaluate a putative adenosinergic mediation. Locomotor activity was measured in the automated activity chamber for 20 min.Acute and repeated dipyridamole reduced the increase in locomotor activity induced by MPH, while allopurinol and inosine had no effect. Aminophylline blocked the effect of dipyridamole in MPH‐induced hyperlocomotion.The present results suggest that dipyridamole may have an antimanic‐like effect through adenosine receptors and reinforce the proposal that the adenosine system may be an interesting target for new antimanic drugs. [ABSTRACT FROM AUTHOR]