title: Hippocampal and prefrontal dopamine D1/5 receptor involvement in the memory-enhancing effect of reboxetine.
abstract: Dopamine modulates cognitive functions through regulation of synaptic transmission and plasticity in the hippocampus and prefrontal cortex (PFC). Thus, dopamine dysfunction in depression may be particularly relevant for the cognitive symptoms. The norepinephrine transporter inhibitor reboxetine facilitates memory processing in both healthy volunteers and in depressed patients and increases dopamine release in both the hippocampus and PFC. We investigated the potential involvement of the hippocampal and PFC dopamine D1/5 receptors in the cognitive effects of reboxetine using the object recognition test in rats. Infusion of the D1/5 antagonist SCH23390 into the dorsal hippocampus or medial PFC prior to the exploration of the objects impaired memory. Conversely, infusion of the D1/5 agonist SKF81297 into the dorsal hippocampus or medial PFC facilitated memory. Reboxetine similarly facilitated recognition memory in healthy rats and the D1/5 antagonist SCH23390 reversed this effect when infused into the dorsal PFC, but not when infused into the hippocampus. Moreover, systemic reboxetine increased the levels of the NMDA subunit GluN2A in the PFC but not in the hippocampus. Finally, we demonstrate that a single dose of reboxetine does not affect immobility in the forced swim test but improves recognition memory in the Flinders sensitive line (FSL) rat model for depression. The present data in rats are in line with effects of reboxetine on memory formation in healthy volunteers and depressed patients and indicate the involvement of PFC dopamine D1/5 receptors.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Dimitri
authors.initials: D
authors.lastname: De Bundel
authors.forename: Teresa
authors.initials: T
authors.lastname: Femenía
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: DuPont
authors.forename: Åsasa
authors.initials: Å
authors.lastname: Konradsson-Geuken
authors.forename: Kritin
authors.initials: K
authors.lastname: Feltmann
authors.forename: Björn
authors.initials: B
authors.lastname: Schilström
authors.forename: Maria
authors.initials: M
authors.lastname: Lindskog
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects*; D013550:Swimming; D013997:Time Factors
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009025:Morpholines; D018697:Nootropic Agents; D000077593:Reboxetine; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D016194:Receptors, N-Methyl-D-Aspartate; C493607:Drd5 protein, rat