Adenosine A 2A receptor antagonism and genetic deletion attenuate the effects of dopamine D 2 antagonism on effort-based decision making in mice

M. Pardo, L. Lopez-Cruz, O. Valverde, C. Ledent, Y. Baqi, C. E. Müller, J. D. Salamone, M. Correa

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Brain dopamine (DA) and adenosine interact in the regulation of behavioral activation and effort-related processes. In the present studies, a T-maze task was developed in mice for the assessment of effort-related decision making. With this task, the two arms of the maze have different reinforcement densities, and a vertical barrier is positioned in the arm with the higher density (HD), presenting the animal with an effort-related challenge. Under control conditions mice prefer the HD arm, and climb the barrier to obtain the larger amount of food. The DA D 2 receptor antagonist haloperidol decreased selection of the HD arm and increased selection of the arm with the low density of reinforcement. However, the HD arm was still the preferred choice in haloperidol-treated mice trained with barriers in both arms. Pre-feeding the mice to reduce food motivation dramatically increased omissions, an effect that was distinct from the actions of haloperidol. Co-administration of theophylline, a nonselective adenosine receptor antagonist, partially reversed the effects of haloperidol. This effect seems to be mediated by the A 2A receptor but not the A 1 receptor, since the A 2A antagonist MSX-3, but not the A 1 antagonist CPT, dose dependently reversed the effects of haloperidol on effort-related choice and on c-Fos expression in the dorsal striatum and nucleus accumbens. In addition, adenosine A 2A receptor knockout mice were resistant to the effects of haloperidol on effort-related choice in the maze. These results indicate that DA D 2 and adenosine A 2A receptors interact to regulate effort-related decision making and effort expenditure in mice.

Original languageEnglish
Pages (from-to)2068-2077
Number of pages10
JournalNeuropharmacology
Volume62
Issue number5-6
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Adenosine A2A Receptors
Haloperidol
Dopamine
Decision Making
Purinergic P1 Receptor Antagonists
Food
Nucleus Accumbens
Theophylline
Health Expenditures
Knockout Mice
Adenosine
Motivation
Brain

Keywords

  • A receptor knockout
  • Anergia
  • Behavioral activation
  • Behavioral economics
  • Motivation
  • T-maze task

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Adenosine A 2A receptor antagonism and genetic deletion attenuate the effects of dopamine D 2 antagonism on effort-based decision making in mice. / Pardo, M.; Lopez-Cruz, L.; Valverde, O.; Ledent, C.; Baqi, Y.; Müller, C. E.; Salamone, J. D.; Correa, M.

In: Neuropharmacology, Vol. 62, No. 5-6, 04.2012, p. 2068-2077.

Research output: Contribution to journalArticle

Pardo, M. ; Lopez-Cruz, L. ; Valverde, O. ; Ledent, C. ; Baqi, Y. ; Müller, C. E. ; Salamone, J. D. ; Correa, M. / Adenosine A 2A receptor antagonism and genetic deletion attenuate the effects of dopamine D 2 antagonism on effort-based decision making in mice. In: Neuropharmacology. 2012 ; Vol. 62, No. 5-6. pp. 2068-2077.
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