G. Martin et al., METABOTROPIC GLUTAMATE RECEPTORS REGULATE N-METHYL-D-ASPARTATE-MEDIATED SYNAPTIC TRANSMISSION IN NUCLEUS-ACCUMBENS, Journal of neurophysiology, 78(6), 1997, pp. 3028-3038
We recorded intracellularly from core nucleus accumbens (NAcc) neurons
in brain slices to study the regulation by metabotropic glutamate rec
eptors (mGluRs) of pharmacologically isolated N-methyl-D-aspartate-med
iated excitatory postsynaptic currents (NMDA-EPSCs). Monosynaptic NMDA
-EPSCs, evoked by local stimulation, were isolated by superfusion of t
he non-NMDA and gamma-aminobutyric acid-4 (GABA(A)) receptor antagonis
ts, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 mu M) and bicuculli
ne (15 mu M), respectively. Trans-1-aminocyclopentane- 1,3-decarboxyli
c acid (trans-ACPD: 50 mu M), a nonspecific group 1 and 2 mGluR agonis
t, had no effect on resting membrane potential (RMP) or input resistan
ce of NAcc neurons. However, it consistently decreased NMDA-EPSC areas
(time integrals) dose dependently (1-100 mu M; EC50 = 8 mu M) and rev
ersibly. The specific group 1 mGluR agonists quisqualate (1-4 mu M) an
d (RS)-3,5-dihydroxyphenylglycine (DHPG; 100 mu M) did not mimic the t
rans-ACPD effect on NMDA-EPSCs, nor did exposure of the slice to the g
roup 1 mGluR antagonist L(+)-2-amino-3-phosphonopropionic acid (L-AP3,
0.4 mM) inhibit the trans-ACPD effect. The putative mGluR1 and mGluR2
antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) at 0.5 mM f
ailed to antagonize trans-ACPD effects but at 1 mM blocked them. Both
the group 2 mGluR agonist (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycin
e (L-CCG-I, 2 mu M) and the group 3 mGluR specific agonist L(+)-2-amin
o-4-phosphonobutyric acid (L-AP4, 20 mu M) attenuated NMDA-EPSC areas;
the effect of L-AP4 was blocked by the group 3 antagonist (S)-2-amino
-2-methyl-4-phosphonobutanoic acid (MAP4; 0.5 mM). Exogenously applied
NMDA, in the presence of tetrodoxin to prevent presynaptic effects, i
nduced inward currents that were decreased by 20 mu M L-AP4 but not by
10 mu M trans-ACPD. These findings suggest that NMDA receptor-mediate
d neurotransmission in NAcc is under dual inhibitory regulation by gro
up 2 and 3 metabotropic receptor subtypes: L-AP4-sensitive receptors l
ocated postsynaptically and those sensitive to trans-ACPD located pres
ynaptically.