We have reported previously that a selective metabotropic glutamate receptor (mGluR) agonist, (1S,3R)-1-aminocyclopentane- 1,9-dicarboxylic acid (1S,3R-ACPD), caused a slow membrane depolarization in rat dorsolateral septal nucleus (DLSN) neurons. Using single electrode voltage-clamp recording methods, we now investigate the pharmacological properties of the receptor that mediates ACPD-induced membrane currents in DLSN neurons recorded from pertussis toxin (PTX)-treated rats. Two pharmacologically distinct inward currents, that is, the ACPD current and Q(m) current, have been identified based on their agonist preference and sensitivity to various antagonists. The ACPD current is blocked by L-2-amino-4-phosphonobutyric acid (L-AP4), but is insensitive to L-aspartic acid-beta-hydroxamate (L-AA beta H), (+)-alpha-methyl-4-carboxyphenylglycine (+)-MCPG), or L-2-amino-3-phosphonopropicnic acid (L-AP3). The Q(m) current is blocked by L-AA beta H and (+)-MCPG, but is insensitive to L-AP3 or L-AP4. These two inward currents distribute differentially within subpopulations of DLSN neurons. The ACPD current is the only current observed in most DLSN ''burster'' neurons, while the Q(m) current is observed more frequently in DLSN ''nonburster'' neurons. The pharmacological profiles of these currents suggest that the Q(m) current is likely mediated by mGluR1 or mGluR5, while the ACPD current is mediated by receptors that are pharmacologically distinct from any of the currently cloned mGluRs.
