title: Disrupting effect of drug-induced reward on spatial but not cue-guided learning: implication of the striatal protein kinase A/cAMP response element-binding protein pathway.
abstract: The multiple memory systems hypothesis posits that different neural circuits function in parallel and may compete for information processing and storage. For example, instrumental conditioning would depend on the striatum, whereas spatial memory may be mediated by a circuit centered on the hippocampus. However, the nature of the task itself is not sufficient to select durably one system over the other. In this study, we investigated the effects of natural and pharmacological rewards on the selection of a particular memory system during learning. We compared the effects of food- or drug-induced activation of the reward system on cue-guided versus spatial learning using a Y-maze discrimination task. Drug-induced reward severely impaired the acquisition of a spatial discrimination task but spared the cued version of the task. Immunohistochemical analysis of the phosphorylated form of the cAMP response element binding (CREB) protein and c-Fos expression induced by behavioral testing revealed that the spatial deficit was associated with a decrease of both markers within the hippocampus and the prefrontal cortex. In contrast, drug reward potentiated the cued learning-induced CREB phosphorylation within the dorsal striatum. Administration of the protein kinase A inhibitor 8-Bromo-adenosine-3',5'-cyclic monophosphorothioate Rp isomer (Rp-cAMPS) into the dorsal striatum before training completely reversed the drug-induced spatial deficit and restored CREB phosphorylation levels within the hippocampus and the prefrontal cortex. Therefore, drug-induced striatal hyperactivity may underlie the declarative memory deficit reported here. This mechanism could represent an important early step toward the development of addictive behaviors by promoting conditioning to the detriment of more flexible forms of memory.
authors.affiliation: Université de Bordeaux and  Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5287, 33405 Talence, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Baudonnat
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guillou
authors.forename: Marianne
authors.initials: M
authors.lastname: Husson
authors.forename: Matthias
authors.initials: M
authors.lastname: Vandesquille
authors.forename: Marc
authors.initials: M
authors.lastname: Corio
authors.forename: Laurence
authors.initials: L
authors.lastname: Decorte
authors.forename: Angélique
authors.initials: A
authors.lastname: Faugère
authors.forename: Yves
authors.initials: Y
authors.lastname: Porte
authors.forename: Nicole
authors.initials: N
authors.lastname: Mons
authors.forename: Vincent
authors.initials: V
authors.lastname: David
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001931:Brain Mapping; D050882:CREB-Binding Protein / Q000378:metabolism*; D002755:Choice Behavior / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003463:Cues; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004192:Discrimination, Psychological / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections / Q000379:methods; D009020:Morphine / Q000008:administration & dosage; D009294:Narcotics / Q000008:administration & dosage; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects
chemical_list: D009294:Narcotics; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D009020:Morphine; D000242:Cyclic AMP; D050882:CREB-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases
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