2-chloro-5-hydroxyphenylglycine and (alpha-carboxycyclopropyl)glycine

The role of metabotropic glutamate receptors (mGluRs) in long-term potentiation (LTP) has remained controversial. However, it has recently been shown that group I mGluR activation, prior to high frequency stimulation (HFS), can facilitate or 'prime' LTP in the area CA1 of the hippocampus. Here we report that, in the dentate gyrus in vitro, activation of both group I and group II mGluRs primes LTP. Control LTP, 60 min after HFS was 145.4+/-3.6% of control. The group I mGluR agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 100 microM), resulted in LTP of 180.1+/-12.1% of control, which was significantly greater than control LTP (n=4; P<0.05). The group I/II mGluR agonist 1S, 3R-1-aminocyclopentate-1,3-dicarboxylic acid (1S,3R-ACPD, 10 microM), and the group II mGluR agonist (2S,3S, 4S)-alpha-(carboxy-cyclopropyl)-glycine (L-CCG-1, 20 microM) also produced LTP that was significantly greater than control LTP (177. 7+/-11.5% and 183.2+/-9.1% of control respectively; n=5; P<0.05). The group III mGluR agonist l-2-amino-4-phosphonobutyric acid (L-AP4, 20 microM), failed to significantly prime LTP (153.8+/-5.9% of control; n=5). It also proved difficult to depotentiate the primed LTP. Following low frequency stimulation (LFS), control LTP was reduced to 101.1+/-3.6% of control, and to 145.0+/-2.1%, 141.2+/-14. 7% and 134.0+/-8.7% of control for CHPG, ACPD and L-CCG-1 primed LTP respectively. We conclude that LTP may be primed by mGluR activation in the dentate gyrus and that this priming is mediated through group I and II mGluRs.

Topics: Amino Acids, Dicarboxylic; Animals; Cycloleucine; Dentate Gyrus; Excitatory Amino Acid Agonists; Excitatory Postsynaptic Potentials; Glycine; In Vitro Techniques; Long-Term Potentiation; Membrane Potentials; Neuroprotective Agents; Phenylacetates; Propionates; Rats; Receptors, Metabotropic Glutamate