PROLONGED STIMULATION OF RESPIRATION BY BRAIN-STEM METABOTROPIC GLUTAMATE RECEPTORS

Stimulation of metabotropic glutamate receptors (mGluRs) in the retrot rapezoid nucleus (RTN) of chloralose-urethan-anesthetized rats by the mGluR agonist (1S,3R)-aminocyclopentanedicarboxylic acid [(1S,3R)-ACPD ; 10 nl, 1 mM] increases integrated phrenic nerve amplitude (PNA) for >60 min. Here we ask if the mGluR antagonist (+/-)-alpha w-methyl-4-ca rboxyphenyl-glycine [(+/-)-MCPG] can block this effect. Using multibar reled micropipettes, we first identified RTN sites that affect respira tion by noting short-lived stimulation of PNA produced by brief-durati on injection of glutamate (10 nl, 100 mM), a presumed ionotropic recep tor response. We then injected the active or inactive isomer of(+/-)-M CPG (10 nl, 10 mM) followed by (1S,3R)-ACPD or by a long-duration (60- s) injection of glutamate (10 nl, 100 mM) at the same site. Each injec tion location was verified anatomically. The active antagonist (+/-)-M CPG itself had no significant effect on PNA, but it blocked 1) subsequ ent (1S,3R)-ACPD-induced PNA stimulation for 99 +/- 11 (SE) min and 2) the PNA response to 60-s glutamate injection for 66 +/- 6 min. The in active form (+/-)-MCPG had no effect on (1S,3R)-ACPD-induced PNA stimu lation. We conclude that 1) RTN mGluRs may be involved in respiratory control, 2) RTN mGluRs are not active in eupnea, and 3) stimulation of RTN mGluRs may require prolonged glutamate release.