DHPG-induced LTD in area CA1 of juvenile rat hippocampus; characterisation and sensitivity to novel mGlu receptor antagonists

Neuropharmacology. 1999 Oct;38(10):1577-83. doi: 10.1016/s0028-3908(99)00123-9.


We have used extracellular microelectrode recording to characterise a form of long-term depression (LTD) of synaptic transmission that can be induced by metabotropic glutamate (mGlu) receptor activation in the CA1 region of the young (12-18 day old) rat hippocampus. Activation of group I mGlu receptors by the specific agonist 3,5-dihydroxyphenylglyine (DHPG) induced LTD of field excitatory postsynaptic potentials (fEPSPs). The mGlu5 selective agonist 2-chloro-5-hydroxyphenylglycine was also capable of inducing LTD. In contrast, the group II specific agonist DCG-IV had no effect on synaptic transmission, whilst the group III receptor agonist (S)-2-amino-4-phosphonobutyrate elicited a depression that reversed fully upon agonist washout. DHPG-induced LTD could still be generated after prior saturation of electrically-induced NMDA receptor-dependent LTD. DHPG-induced LTD was reversed by tetanic stimulation comprising 100 shocks delivered at 100 Hz. A novel mGlu receptor antagonist, (RS)-2-amino-2-(3-cis and trans-carboxycyclobutyl-3-(9-thioxanthyl)propionic acid) (LY393053) that potently inhibits mGlu1 and mGlu5 receptors, prevented the induction of DHPG-induced LTD. Like other mGlu receptor antagonists, LY393053 also reversed pre-established DHPG-induced LTD. In contrast, a potent mGlu1 selective antagonist (S)-2-methyl-4-carboxyphenylglycine (LY367385) did not prevent the induction of DHPG-induced LTD. In conclusion, DHPG, probably via activation of mGlu5 receptors, is able to induce a robust form of LTD in the CA1 region of the young rat hippocampus that is mechanistically distinct from NMDA receptor-dependent homosynaptic LTD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Phenylacetates / pharmacology
  • Propionates / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists*
  • Structure-Activity Relationship


  • 2-amino-4-phosphono-propinate
  • 2-chloro-5-hydroxyphenylglycine
  • Excitatory Amino Acid Antagonists
  • Phenylacetates
  • Propionates
  • Receptors, Metabotropic Glutamate
  • Methoxyhydroxyphenylglycol
  • Glycine
  • 3,4-dihydroxyphenylglycol