TY - JOUR
T1 - Adenosine A 2A receptor antagonism and genetic deletion attenuate the effects of dopamine D 2 antagonism on effort-based decision making in mice
AU - Pardo, M.
AU - Lopez-Cruz, L.
AU - Valverde, O.
AU - Ledent, C.
AU - Baqi, Y.
AU - Müller, C. E.
AU - Salamone, J. D.
AU - Correa, M.
N1 - Funding Information:
John D. Salamone has received compensation from Merck-Seronno and Pfizer. Christa E. Müller has received funding by UCB Pharma within the Biopharma collaborative project Neuroallianz funded by the German Federal Ministry of Education and Research (BMBF).
Funding Information:
This work was supported by a grant to Mercè Correa from Fundació Bancaixa-UJI ( P1.1B2010-43 ), to John D. Salamone from the National Institute of Mental Health ( MH078023 ), to Olga Valverde from MCINN ( SAF2010-1593 ) and ISCIII RTA ( RD06/0001/1001 ). Christa E. Müller and Younis Baqi were funded by the BMBF , 01EW0911 in the framework of ERA-NET-NEURON. Marta Pardo and Laura Lopez-Cruz were supported by personal grants awarded by Fundació Bancaixa-UJI .
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - A receptor knockout
KW - Anergia
KW - Behavioral activation
KW - Behavioral economics
KW - Motivation
KW - T-maze task
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U2 - 10.1016/j.neuropharm.2011.12.033
DO - 10.1016/j.neuropharm.2011.12.033
M3 - Article
C2 - 22261384
AN - SCOPUS:84857055627
SN - 0028-3908
VL - 62
SP - 2068
EP - 2077
JO - Neuropharmacology
JF - Neuropharmacology
IS - 5-6
ER -