Journal
NEUROPHARMACOLOGY
Volume 75, Issue -, Pages 437-444Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2013.08.006
Keywords
Operant conditioning; Incentive salience attribution; MP-10; Selective PDE10A Antagonist; Medium spiny neurons; Striatum
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Funding
- Janssen Research Foundation
- federal science fund FWO [G.0746.13N]
- KU Leuven research council (GOA)
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The pharmacological effect of the selective PDE10A inhibitor 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline succinic acid (MP-10) on aversively and appetitively motivated behavior in C57BL/6J mice was examined. MP-10 dose-dependently impaired performance on a highly demanding reward schedule during appetitive conditioning. The compound further affected cue-based, but not contextual aversive conditioning. Finally, dose-dependent impaired performance in an instrumentally conditioned reinforcement (ICR) task was found. This suggests that the observed behavioral effects of MP-10 can be at least partially ascribed to impaired incentive salience attribution. MP-10 administration dose-dependently enhanced striatal expression of the immediate early gene Zif268, which suggest that MP-10 affects the studied motivated behaviors by enhancing PDE10A-regulated striatal signaling. Striatal signaling thus appears to be crucial in processes that control reward-motivated behavior in general, and incentive salience attribution in particular. Continued research will prove valuable towards a better understanding of psychopathologies that affect reward-motivated behaviors, such as drug addiction and schizophrenia. (C) 2013 Elsevier Ltd. All rights reserved.
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