Group II and III metabotropic glutamate receptors suppress excitatory synaptic transmission in the dorsolateral bed nucleus of the stria terminalis

Neuropsychopharmacology. 2005 Jul;30(7):1302-11. doi: 10.1038/sj.npp.1300672.

Abstract

Conditions such as anxiety, drug abuse, and post-traumatic stress disorder are thought to reflect alterations in central nervous system stress and reward circuitry. Recent evidence suggests a key component of this circuitry is the bed nucleus of the stria terminalis (BNST). In particular, regulation of glutamatergic transmission in the BNST plays a critical role in animal performance on anxiety tasks. Metabotropic glutamate receptors (mGluRs) have been implicated in stress and drug addiction and are known to regulate glutamatergic transmission in many brain regions. We have utilized both extracellular field potential and whole-cell patch-clamp recording in an in vitro slice preparation of mouse dorsal anterolateral BNST to determine whether G(i/o)-linked mGluRs modulate excitatory transmission in this region. We find that activation of group II and group III mGluRs in an in vitro slice preparation of the dBNST causes a depression of excitatory transmission. The depression evoked by group II mGluR activation may represent a form of synaptic plasticity as prolonged activation of the receptor produces a long-term depression of glutamatergic transmission. Based on paired-pulse ratio analysis, initiation of depression by group II and group III mGluR subfamilies appears to, at least in part, involve decreased glutamate release. In total, our data suggest a plausible site of action for some of the anxiolytic effects of group II and group III mGluR agonists.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Drug Interactions
  • Electric Stimulation / methods
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Mice
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Patch-Clamp Techniques / methods
  • Presynaptic Terminals / drug effects
  • Receptors, Metabotropic Glutamate / physiology*
  • Septal Nuclei / cytology
  • Septal Nuclei / drug effects
  • Septal Nuclei / physiology*
  • Sodium Channel Blockers / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Tetrodotoxin / pharmacology
  • Time Factors

Substances

  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • Sodium Channel Blockers
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
  • Tetrodotoxin