Group II and III metabotropic glutamate receptors modulate paired pulse depression in the rat dentate gyrus in vitro

• Published in: European journal of pharmacology Vol. 340; no. 1; pp. 35 - 44
• Main Authors: O'Leary, Deirdre M, Cassidy, Eugene M, O'Connor, John J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.12.1997; Elsevier
• Subjects: 1 S,3 R-ACPD (1 S,3 R-1-aminocyclopentate-1,3-dicarboxylic acid); Amino Acids, Dicarboxylic - pharmacology; Aminoacid receptors (glycine, glutamate, gaba); Aminobutyrates - pharmacology; Animals; Benzoates - pharmacology; Biological and medical sciences; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cycloleucine - analogs & derivatives; Cycloleucine - pharmacology; Cyclopropanes - pharmacology; DCG-IV ((2 S,1′ R,2′ R,3′ R)-2-2′,3′-dicarboxy cyclopropylglycine); Dentate Gyrus - drug effects; Dentate Gyrus - metabolism; Evoked Potentials, Somatosensory - drug effects; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Fundamental and applied biological sciences. Psychology; Glycine - analogs & derivatives; Glycine - pharmacology; Hippocampal slice; In Vitro Techniques; l-AP4 ( l-2-amino-4-phosphonobutyric acid); MCPG ( α-methyl carboxy–phenylglycine); mGlu receptor; Molecular and cellular biology; Neuroprotective Agents - pharmacology; Paired pulse depression; Rats; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Resorcinols - pharmacology; Vertebrates: nervous system and sense organs; α-Methyl- l-AP4 ( α-methyl- l-amino-4-phosphonobutyric acid); 1 S,3 R-ACPD (1 S,3 R-1-aminocyclopentate-1,3-dicarboxylic acid); l-AP4 ( l-2-amino-4-phosphonobutyric acid); DCG-IV ((2 S,1′ R,2′ R,3′ R)-2-2′,3′-dicarboxy cyclopropylglycine); Hippocampal slice; α-Methyl- l-AP4 ( α-methyl- l-amino-4-phosphonobutyric acid); Paired pulse depression; mGlu receptor; MCPG ( α-methyl carboxy–phenylglycine); Rat; Depressions; Rodentia; Central nervous system; Electrophysiology; Glutamate receptor; In vitro; Neuromodulation; Mechanism; Vertebrata; Dentate gyrus; Regulation(control); Mammalia; Metabotropic receptor; Paired stimulation; Synaptic transmission; Animal; Synaptic plasticity; Subtype; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)01405-2

We have investigated the effect of a number of group I, II and III metabotropic glutamate (mGlu) receptor agonists and antagonists on paired pulse depression in the medial perforant path of the rat dentate gyrus in vitro. A triphasic pattern of a large depression at short intervals (10–50 ms), a reduction of this depression at intermediate intervals (50–200 ms) and again a large depression at late intervals (>200 ms) was observed. The group I mGlu receptor agonist, ( S)-3,5-dihydroxy phenylglycine (( S)-DHPG; 20 μM) had no significant effect on paired pulse depression at any interstimulus intervals. The mGlu receptor group II and III agonists, l-CCG-1 ((2 S,3 S,4 S)- α-(carboxy–cyclopropyl)-glycine), DCG-IV ((2 S,1′ R,2′ R,3′ R)-2-2′,3′-dicarboxy cyclopropylglycine), 1 S,3 R-ACPD (1 S,3 R-1-aminocyclopentate-1,3-dicarboxylic acid) and l-AP4 ( l-2-amino-4-phosphono butyric acid) reduced paired pulse depression at interstimulus intervals of 200 ms or less. Application of the non specific mGlu receptor antagonist, MCPG ( α-methyl carboxy–phenylglycine; 200 μM) completely inhibited the 1S,3R ACPD-induced reduction in paired pulse depression but was without effect on the l-AP4 response. The relatively specific group II antagonist MCCG ((2 S,3 S,4 S)-2-methyl-2-carboxy cycloproprylglycine) at 200 μM and 500 μM, attenuated but did not completely inhibit the DCG-IV induced reduction of paired pulse depression. The putative group III pre-synaptic mGlu receptor antagonist α-methyl- l-AP4 and MSOP (( R S)- α-methylserine- O-phosphate) both at 200 μM inhibited the l-AP4-induced reduction in paired pulse depression at intermediate phase interstimulus intervals but not at early interstimulus intervals. These results specifically demonstrate the involvement of group II and III mGlu receptor ligands in the modulation of paired pulse depression in the medial perforant pathway.