[대학원 생명과학과 세미나 안내]
연사 : 최두섭 교수 (Mayo Clinic College of Medicine)
연제 : Adenosine A2A Receptor Driven Impulsivity and Adult Hippocampal Neurogenesis
일시 : 2016년 7월 7일 (목) 오후 4시
장소 : 하나과학관 A동 109호
초청교수 : 백자현 교수
Abstract
Dampened adenosine A2A receptor (A2AR) function has been implicated in addiction through enhancement of goal-directed behaviors. However, the contribution of the A2AR to the control of impulsive reward seeking remains unknown. Using mice that were exposed to differential reward of low rate (DRL) schedules during Pavlovian conditioning, second-order schedule discrimination, and the 5-choice serial reaction time task (5-CSRTT), we demonstrate that deficits of A2AR function promote impulsive responses. Antagonism of the A2AR lowered ERK1/2 phosphorylation in the dorsal hippocampus (dHip) and potentiated impulsivity during Pavlovian conditioning and the 5-CSRTT. Remarkably, inhibition of ERK1/2 phosphorylation by U0126 in the dHip prior to Pavlovian conditioning exacerbated impulsive reward seeking. Interestingly, we found decreased A2AR expression and reduced ERK1/2 phosphorylation in the dHip of ENT1–/– mice, a rodent model of excessive alcohol consumption which naturally displayed exacerbated impulsivity. To determine whether impulsive response behavior is associated with adult hippocampal neurogenesis, we examined BrdU and doublecortin-x (DCX) expression following 5-CSRTT testing. These studies revealed that impulsive behavior driven by inhibition of the A2AR is accompanied by increased DCX+ expression in the hippocampus, suggesting that aberrant hippocampal neurogenesis may contribute to the development of maladaptive reward-seeking behaviors.