ISSN:
1460-9568
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Anatomical, biochemical and electrophysiological studies have previously shown that cortico-striatal terminals contain abundant presynaptic group 2 metabotropic glutamate (mGlu) receptors. Using brain slices we have previously shown that these receptors inhibit depolarization-induced transmitter release. Using microdialysis in freely moving rats, we now report the effects of group 2 mGlu receptor agonists and antagonists on glutamate concentration in the caudate extracellular fluid. A mild decrease (20–30%) in glutamate concentration in caudate dialysates was observed when 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid or (2S,3S,4S)-α-carboxycyclopropyl-glycine (L-CCG-1), mGlu receptor agonists, was locally administered. On the contrary, α-methyl-4-carboxyphenylglycine, an antagonist of type 1 and type 2 mGlu receptors, increased the glutamate concentration in dialysates by up to 3.5-fold, and its effects were prevented by the simultaneous administration of L-CCG-1, a preferential type 2 mGlu receptor agonist. A significant increase of glutamate output in striatal dialysate was also found after local administration of (2S,1′S,2′S,3′R)-2-(2′-carboxy-3′-phenylcyclopropyl)glycine, another structurally unrelated, relatively selective and potent type 2 mGlu receptor antagonist. The results suggest that type 2 mGlu receptors tonically inhibit transmitter release from corticostriatal terminals. Since the cortico-striatal pathway profoundly affects the function of a large percentage of caudate neurons, it is reasonable to predict that the use of selective type 2 mGlu receptor agents will be helpful for scientific and therapeutic studies on the physiopathology of basal ganglion disorders.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1460-9568.1997.tb01489.x
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