Caffeine is an adenosine receptor antagonist and the most commonly used psychostimulant functioning through enhancing striatal dopamine signaling. In vitro evidence reveals that adenosine 1A (A₁R) and 2A receptors (A_2AR) in the striatum form functional heterodimers respectively with dopamine D1 (D₁R) and D2 receptors (D₂R) and exert allosteric antagonism. Adenosinergic modulation therefore is believed to be critically involved in dopamine-associated psychiatric disorders. However, in vivo characterization of adenosine-dopamine interactions and its modulation of neurocognitive functions remain scarce. In a joint project between Mass General Hospital and University Psychiatric Clinics Basel, we characterized adenosine-dopamine interactions using multimodal pharmacological imaging and pharmacobehavioral models. First, we examined changes in D₂R availability and the associated hemodynamic response to rewards, using [¹¹C]Raclopride PET/fMRI after acute caffeine administration. Further, to understand the adaption in adenosine-dopamine modulation over chronic adenosine antagonism, we measured positive and negative reinforcement learning after subchronic caffeine intake compared to acute caffeine and placebo. We found that caffeine acutely increased striatal D₂R availability and elevated neural activity in medial prefrontal cortex, anterior and middle cingulate cortices, and hippocampus during reward feedback. Furthermore, caffeine generally improved learning outcomes, with an accelerated learning curve in acute caffeine condition. Interestingly, subchronic caffeine enhanced positive reinforcement learning whereas acute caffeine worsened it. Exploratory analyses suggested that acute caffeine elevated salience towards positive reinforcers, thereby blurring the distinction between different reinforcement strengths. Our data highlight the adenosine-dopamine interaction and its modulation of neurocognitive functions.