Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal neuroblast proliferation

A. Oliveros, C. H. Cho, A. Cui, S. Choi, D. Lindberg, D. Hinton, Mi-Hyeon D Jang, Doo Sup Choi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Dampened adenosine A2A receptor (A2A R) function has been implicated in addiction through enhancement of goal-directed behaviors. However, the contribution of the A2A R 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 A2A R function promote impulsive responses. Antagonism of the A2A R lowered ERK1 and ERK2 phosphorylation in the dorsal hippocampus (dHip) and potentiated impulsivity during Pavlovian-conditioning and the 5-CSRTT. Remarkably, inhibition of ERK1 and ERK2 phosphorylation by U0126 in the dHip prior to Pavlovian-conditioning exacerbated impulsive reward seeking. Moreover, we found decreased A2A R expression, and reduced ERK1 and ERK2 phosphorylation in the dHip of equilibrative nucleoside transporter type 1 (ENT1-/-) null mice, which displayed exacerbated impulsivity. To determine whether impulsive response behavior is associated with hippocampal neuroblast development, we investigated expression of BrdU+ and doublecortin (DCX+) following 5-CSRTT testing. These studies revealed that impulsive behavior driven by inhibition of the A2A R is accompanied by increased neuroblast proliferation in the hippocampus.

Original languageEnglish (US)
Article numbere1095
JournalTranslational Psychiatry
Volume7
Issue number4
DOIs
StatePublished - Jan 1 2017

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Adenosine A2A Receptors
Impulsive Behavior
Hippocampus
Reward
Reaction Time
Phosphorylation
Appointments and Schedules
Bromodeoxyuridine
Conditioning (Psychology)
Inhibition (Psychology)

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal neuroblast proliferation. / Oliveros, A.; Cho, C. H.; Cui, A.; Choi, S.; Lindberg, D.; Hinton, D.; Jang, Mi-Hyeon D; Choi, Doo Sup.

In: Translational Psychiatry, Vol. 7, No. 4, e1095, 01.01.2017.

Research output: Contribution to journalArticle

Oliveros, A. ; Cho, C. H. ; Cui, A. ; Choi, S. ; Lindberg, D. ; Hinton, D. ; Jang, Mi-Hyeon D ; Choi, Doo Sup. / Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal neuroblast proliferation. In: Translational Psychiatry. 2017 ; Vol. 7, No. 4.
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