ACPD-mediated slow-onset potentiation is associated with cell death in the rat CA1 region in vivo.
Slow-onset potentiation of synaptic transmission in the hippocampus in vitro and in vivo is induced by application of the metabotropic glutamate receptor (mGluR) agonist, 1S,3R-amino cyclopentane 2,3-dicarboxylic acid (ACPD). This study investigated the cellular response in the CA1 region of freely moving rats to ACPD application. Drugs were applied via the lateral cerebral ventricle, and measurements were obtained from the CA1 region via permanently implanted electrodes. ACPD (20 nmol/5 microl) produced a dose-dependent slow-onset potentiation in the CA1 region which lasted over 4 h. Histological evaluation at either 4 h or 7 days following ACPD-injection indicated that slow-onset potentiation was associated with gradual but marked cell death in the CA1 region. Whereas 20 nmol ACPD produced significant CAI neurotoxicity, concentrations which did not induce potentiation had little or no neurotoxic effect. Both the general mGluR antagonist R,S-alpha-methyl-carboxyphenylglycine (1 micromol/5 microl), and the group 1 mGluR antagonist (S)-4-carboxyphenylglycine (4CPG, 100 nmol/5 microl) significantly inhibited ACPD-induced neuropathology. In addition, 4CPG inhibited the expression of ACPD-mediated slow-onset potentiation. These results confirm previous findings that in the CA1 region in vivo, slow-onset potentiation is mediated group 1 mGluRs, and indicate that slow-onset potentiation may involve pathological processes.
Manahan-Vaughan
D
D
Department of Neurophysiology, Federal Institute for Neurobiology, Magdeburg, Germany. manahan@ifn-magdeburg.de
Behnisch
T
T
Reymann
K G
KG
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; C079693:4-carboxyphenylglycine; D005998:Glycine