Transient activation of the CA3 Kappa opioid system in the dorsal hippocampus modulates complex memory processing in mice.
The hippocampus plays a central role in various forms of complex learning and memory. Opioid peptides and receptors are abundant in the hippocampus. These peptides are co-released with glutamate from mossy fiber- and lateral perforant path-synapses. In this study, we evaluated the functional relevance of the CA3 Kappa opioid receptors (KOR) by transient pharmacological activation or inactivation using single bilateral intrahippocampal microinjections of a selective agonist (U50,488H, 1 or 2.5 nmol), a selective antagonist (nor-binaltorphimine, norBNI 5 nmol) or a mixture of both. C57Bl/6J mice were tested in a fear conditioning paradigm (FC) or in a modified version of the water maze task thought to reveal how flexibly animals can learn and manipulate spatial information (WM). In FC, the agonist (2.5 nmol) decreased context-induced (but not tone-induced) freezing whereas norBNI had no effect. The impairment caused by the agonist U50,488H was blocked by the injection of norBNI, suggesting that overstimulation of CA3-KOR impairs the acquisition and consolidation of contextual fear-related memory. In the WM task, mice were trained repeatedly each day to find a hidden platform. After having reached this goal, the platform position was changed the next day for a new task. U50,488H injection before the last task abolished the previously acquired ability to find rapidly a new platform location, whereas adding norBNI reversed this impairment. Thus, in the mouse, even partial and topographically restricted activation of CA3-KOR entails impairments in two different hippocampus-dependent tasks, indicating functional relevance of the kappa opioid system.
Daumas
Stéphanie
S
Centre de Recherches sur la Cognition Animale, CNRS UMR 5169, Université Paul Sabatier, Bâtiment 4R3 UFR SVT, Toulouse cedex, France. sdaumas@staffmail.ed.ac.uk <sdaumas@staffmail.ed.ac.uk>
Betourne
Alexandre
A
Halley
Hélène
H
Wolfer
David P
DP
Lipp
Hans-Peter
HP
Lassalle
Jean-Michel
JM
Francés
Bernard
B
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005239:Fear; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer