Time and sex-dependent effects of an adenosine A2A/A1 receptor antagonist on motivation to self-administer cocaine in rats

► Adenosine A2A/A1 receptor blockade with ATL444 alters motivation for cocaine. ► In females, ATL444 treatment acutely increased motivation for cocaine. ► In males, ATL444 treatment produced long-term decreases in motivation for cocaine. ► A2A/A1 blockade mediates time and sex-dependent effects on cocaine reinforcement.