title: L-2-amino-4-phosphonobutanoic acid and 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid reduce paired-pulse depression recorded from medial perforant path in the dentate gyrus of rat hippocampal slices.
abstract: The perforant path is the major excitatory cortical projection to the hippocampal dentate gyrus. Field potentials from the medial perforant path exhibit paired-pulse depression when evoked at interstimulus intervals of 40 to 800 msec. We found that an early component of paired-pulse depression recorded at interstimulus intervals of 40 to 100 msec from slices of rat hippocampus was reduced by L-2-amino-4-phosphonobutanoic acid (L-AP4) (20 microM) without a change in the size of the first field potential in the pair. Paired-pulse depression evoked at intervals of 200 to 800 msec was not reduced. 1S,3R-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), DL-2-amino-3-phosphonopropionic acid and carbachol also reduced paired-pulse depression in a manner similar to L-AP4. Picrotoxin, phaclofen, theophylline or atropine did not reduce paired-pulse depression. Furthermore, paired-pulse depression (40-100 msec) does not appear to involve glutamate uptake or N-methyl-D-aspartate receptors as L-alpha-aminoadipate did not alter paired-pulse depression and neither trans-L-pyrrolidine-2,4-dicarboxylate and L-alpha-aminoadipate nor D-2-amino-5-phosphonopropionic acid blocked the effect of L-AP4 on paired-pulse depression. 4-Aminopyridine inhibits a potassium current that has a similar time course to the L-AP4-induced reduction of paired-pulse depression, however, paired-pulse depression was increased with exposure to 4-aminopyridine. These results indicate that the mechanism underlying paired-pulse depression consists of two components, the early component being reduced by L-AP4, 1S,3R-ACPD, DL-2-amino-3-phosphonopropionic acid and carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Psychobiology, Irvine Research Unit in Brain Aging, University of California.
authors.forename: J S
authors.initials: JS
authors.lastname: Kahle
authors.forename: C W
authors.initials: CW
authors.lastname: Cotman
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003864:Depression, Chemical; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013806:Theophylline / Q000494:pharmacology
chemical_list: D000613:Aminobutyrates; D001285:Atropine; D001418:Baclofen; D002217:Carbachol; D003515:Cycloleucine; D005971:Glutamates; D018698:Glutamic Acid; D014179:Neurotransmitter Uptake Inhibitors; D010852:Picrotoxin; D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D013806:Theophylline; C052329:phaclofen; C036361:1-amino-1,3-dicarboxycyclopentane; C012729:2-amino-4-phosphonobutyric acid