Activation of group II metabotropic glutamate receptors induces depotentiation in amygdala slices and reduces fear-potentiated startle in rats.
There is a close correlation between long-term potentiation (LTP) in the synapses of lateral amygdala (LA) and fear conditioning in animals. We predict that reversal of LTP (depotentiation) in this area of the brain may ameliorate conditioned fear. Activation of group II metabotropic glutamate receptors (mGluR II) with DCG-IV induces depotentiation in the LA. The induction of depotentiation is independent of NMDA receptors, L-type Ca++ channels, and calcineurin activity, but requires presynaptic activity and extracellular Ca++. (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) depotentiation is accompanied by a decrease in the frequency but not the amplitude of miniature excitatory post-synaptic currents (mEPSCs) and could be mimicked by endogenously released glutamate. DCG-IV inhibited the release of glutamate evoked by 4-AP but not that evoked by ionomycin, suggesting that the effect of DCG-IV is not mediated by an action downstream of Ca++ entry. Intra-amygdala infusion of mGluR II agonist blocks the consolidation of fear memory measured with fear-potentiated startle. Taken together, the present results characterize the properties of DCG-IV depotentiation and reveal a close parallel between depotentiation in the amygdala slice and the reduction of conditioned fear in animals.
Lin
Chia-Ho
CH
Department of Pharmacology, National Cheng-Kung University, Tainan, Taiwan 701.
Lee
Chia-Ching
CC
Huang
Ya-Chun
YC
Wang
Su-Jane
SJ
Gean
Po-Wu
PW
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003521:Cyclopropanes / Q000008:administration & dosage; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D005998:Glycine