Lack of expression of long-term potentiation in the dentate gyrus but not in the CA1 region of the hippocampus of μ-opioid receptor-deficient mice

• Published in: Neuropharmacology 2000-05, Vol.39 (6), p.952-960
• Main Authors: Matthies, Henry, Schroeder, Helmut, Becker, Axel, Loh, Horace, Höllt, Volker, Krug, Manfred
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Binding assay; Biological and medical sciences; Cell receptors; Cell structures and functions; Central nervous system; Corpus Striatum - metabolism; Corpus Striatum - ultrastructure; Dentate Gyrus - physiology; Electrophysiology; Female; Funaltrexamine; Fundamental and applied biological sciences. Psychology; Hippocampus; Hippocampus - anatomy & histology; Hippocampus - physiology; In Vitro Techniques; Long-Term Potentiation; Male; Mice; Mice, Mutant Strains; Miscellaneous; Molecular and cellular biology; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - metabolism; Receptors, Glutamate - metabolism; Receptors, Opioid, mu - deficiency; Receptors, Opioid, mu - genetics; Synaptic Membranes - metabolism; Synaptic plasticity; Vertebrates: nervous system and sense organs; μ-opioid receptor; μ-opioid-deficient mutant mice
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(99)00203-8

The possible involvement of the μ-opioid receptor subtype in mechanisms of long-term potentiation (LTP) of the lateral perforant pathway to the dentate gyrus neurons, as well as of the Schaffer collateral–commissural input of CA1 neurons, was investigated using μ-opioid receptor-deficient mutant mice. In transversal hippocampal slices from mice lacking the μ-opioid receptor (MOR) only a short potentiation in the dentate gyrus after tetanization of the lateral perforant pathway was found. In contrast, the loss of the μ-opioid receptor in the CA1 region did not affect the potentiation of the field potentials induced by tetanization of the Schaffer collaterals. In parallel experiments, the application of 10 μM of the selective MOR-antagonist, funaltrexamine, decreased LTP in the dentate gyrus of wild-type mice but again did not alter the potentiation of the field potentials in the CA1. The loss of MOR-binding in the hippocampus was accompanied by a reduction in D2-binding sites indicating a possible compensatory role of the dopaminergic system. The D1- and glutamate binding was not affected. These observations confirm earlier results with pharmacological blockade of opioid receptors in the dentate gyrus and demonstrate an essential role of MOR activation for the generation of LTP in the dentate gyrus of the mouse but not necessarily in the CA1 region.