Transient activation of the CA3 Kappa opioid system in the dorsal hippocampus modulates complex memory processing in mice

Neurobiol Learn Mem. 2007 Jul;88(1):94-103. doi: 10.1016/j.nlm.2007.02.001. Epub 2007 Mar 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / administration & dosage
  • Analysis of Variance
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology*
  • Dose-Response Relationship, Drug
  • Fear
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory / drug effects
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Microinjections
  • Naltrexone / administration & dosage
  • Naltrexone / analogs & derivatives
  • Receptors, Opioid, kappa / agonists
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Receptors, Opioid, kappa / physiology*
  • Spatial Behavior / drug effects
  • Spatial Behavior / physiology


  • Receptors, Opioid, kappa
  • norbinaltorphimine
  • Naltrexone
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer