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Vol. 6, No. 2, pp. 138-152, March/April 1999
1 Department of Neurophysiology, 2 Project
Group Neuropharmacology, 3 Laboratory of Behavioral
Pharmacology, Leibniz Institute for Neurobiology
39008, Magdeburg, Germany; 4 Research Institute for
Applied Neurosciences GmbH, 39120 Magdeburg, Germany
Metabotropic glutamate receptors (mGluRs) have
been implicated in long-term potentiation and in learning and memory
formation. In this study, we tested the effects of group I mGluR
inhibition on synaptic plasticity and learning of rats at different
levels of organization (1) in the hippocampal slice preparation; (2) in
freely moving animals implanted with chronic hippocampal electrodes; and (3) in different spatial learning paradigms. To allow a direct comparison of the effects obtained the same doses were used in all
paradigms. Bath-application of the selective group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) impaired a
decremental long-term potentiation (LTP) induced by a weak tetanization
paradigm, but failed to affect a robust LTP generated by strong
tetanization. In contrast, 4-CPG impaired a robust LTP in freely moving
animals if applied 30 min before tetanization. The same dose of 4-CPG only impeded spatial learning mildly in the eight-arm radial maze and
had no effect on a simple configuration of the Y-maze spatial alternation task. In the more difficult configuration of this task,
however, 4-CPG caused complete amnesia. The lack of state-dependent 4-CPG actions and the absence of any 4-CPG effects in the open-field test classify the obtained retention deficit as a selective impairment of memory storage. Our results indicate a specific role of group I
mGluRs in certain types of synaptic plasticity and of spatial learning.
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