title: Impairments of exploration and memory after systemic or prelimbic D1-receptor antagonism in rats.
abstract: D1-receptor antagonism is known to impair rodent memory but also inhibits spontaneous exploration of stimuli to be remembered. Hypo-exploration could contribute to impaired memory by influencing event processing. In order to explore this effect, the D1 receptor antagonist, SCH23390, was administered to rats via routes that either did or did not affect spontaneous exploration: systemic or prelimbic administration, respectively. Effects were tested in spatial and non-spatial memory tasks selected for their requirements for self-initiated exploration of stimuli to be remembered in order to examine the effects on memory: cross-maze and object recognition task. Systemic administration reduced spatial exploration in cross-maze as well as in an open field test, and also reduced object exploration. Spatial (hippocampus-dependent) short-term memory was inhibited in the cross-maze and non-spatial short-term object retention was also impaired. In contrast to these systemic effects, bilateral injections of SCH23390 into the prelimbic cortices altered neither spatial nor object exploration, but did inhibit short-term memory in both cross-maze and object recognition task. Therefore, the inhibiting effects of SCH23390 on both spatial and non-spatial memory were not mediated indirectly via reduced exploration of stimuli to be remembered, but through antagonism of a prelimbic D1-R function that is directly involved in memory formation. Finally, a cooperative regulation of spatial exploration between D1-R and mGlu5 was indicated by a synergistic effect of the antagonists SCH23390 and MPEP.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bettina
authors.initials: B
authors.lastname: Clausen
authors.forename: Todd R
authors.initials: TR
authors.lastname: Schachtman
authors.forename: Louise T
authors.initials: LT
authors.lastname: Mark
authors.forename: Mette
authors.initials: M
authors.lastname: Reinholdt
authors.forename: Gert R J
authors.initials: GR
authors.lastname: Christoffersen
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004789:Enzyme Activation / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008032:Limbic System / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000502:physiology*; D008845:Microinjections; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D001552:Benzazepines; D017362:Cyclic AMP Response Element-Binding Protein; D018492:Dopamine Antagonists; D004343:Drug Implants; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D017447:Receptors, Dopamine D1; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; C534628:SCH 23390; C121465:6-methyl-2-(phenylethynyl)pyridine; D019950:Mitogen-Activated Protein Kinase 1; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases