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

The possible involvement of the mu-opioid receptor subtype in mechanisms of long-term potentiation (LTP) of the lateral perforant pathway to the denta te gyms neurons, as well as of the Schaffer collateral-commissural input of CA1 neurons, was investigated using mu-opioid receptor-deficient mutant mi ce. In transversal hippocampal slices from mice lacking the mu-opioid recep tor (MOR) only a short potentiation in the dentate gyms after tetanization of the lateral perforant pathway was found. In contrast, the loss of the mu -opioid receptor in the CA1 region did not affect the potentiation of the f ield potentials induced by tetanization of the Schaffer collaterals. In par allel experiments, the application of 10 mu M of the selective MOR-antagoni st, funaltrexamine, decreased LTP in the dentate gyrus of wild-type mice bu t 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 i n D2-binding sites indicating a possible compensatory role of the dopaminer gic system. The D1- and glutamate binding was not affected. Those observati ons confirm earlier results with pharmacological blockade of opioid recepto rs 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 necess arily in the CA1 region. (C) 2000 Elsevier Science Ltd. All rights reserved .