Adenosine A2A receptor (A2AR) antagonists are known to increase hippocampal neurogenesis and goal-directed reward-seeking behaviors. However, the connection between neurogenesis and goal-directed behaviors remained unknown. To study the possible causal relationship, first, we sought to examine whether the A2AR antagonist, istradefylline, which is also recently approved for treating Parkinson’s disease. First, 20 mice were divided into two groups. The first group (10 mice) was injected intraperitoneally (i.p.) daily with istradefylline at 5 mg/kg per day, an hour before behavioral testing. The second group (10 mice) was administered the vehicle. To train the mice toward goal- directed behavior, we used a random ratio (RR) training schedule using a 20% sucrose solution. To evaluate goal-directed or habitual reward-seeking behaviors, we examined nosepoke-based reward-seeking on valued (V) and devalued (DV) conditioning in an extinction test (no reward delivery upon nosepoking) after the training was completed. Goal-directed mice showed a sensitivity to outcome devaluation (stop nosepoking on DV condition). Also, we performed the open field test (OFT) to measure locomotor activity and a Y-maze test to test cognitive function. Our results showed that istradefylline-treated mice exhibited increasing trends of goal-directed behaviors and locomotor activities. Future experiments with additional mice will reveal the role of potentiating goal-directed behaviors and possible correlation with neurogenesis.
