Metabotropic glutamate (mGlu) receptors modulating amino acid outflow were examined in a model system in order to further characterize the pharmacological nature of the mGlu receptors involved in viscerosensory processing in the nucleus tractus solitarii. The actions of a number of subtype-selective mGlu receptor agonists and antagonists were monitored on the K+-evoked outflow of [3H]D-aspartate and [14C]gamma-aminobutyric acid (GABA) from superfused slices of rat nucleus tractus solitarii. (+/-)1S,3R-1-Amino-cyclopentane-1,3-dicarboxylate (10-300 microM), produced a concentration-dependent increase in outflow, which was attenuated by a number of phenylglycine antagonists. (2S,3S,4S)-alpha-(Carboxycyclopropyl)-glycine (30-300 microM) had mixed effects on outflow. The type I-selective agonist (RS)-3,5-dihydroxyphenylglycine (300 microM) also increased outflow and these effects were reversed by the type I antagonist (RS)-1-aminoindan-1,5-dicarboxylate (100 microM). Activation of type II mGlu receptors with (2R,4R)-aminopyrrolidine-2,4-dicarboxylate (300 microM), however, decreased outflow, and this effect was antagonized by the type II antagonist LY307452 (200 microM). Interestingly, LY307452 (200 microM) alone, enhanced outflow of [3H]D-aspartate, but not [14C]GABA. Type III mGlu receptors may not be involved in outflow of [3H]D-aspartate and [14C]GABA in the nucleus tractus solitarii, as L-2-amino-4-phosphonobutyrate (30-300 microM) had no effect under the present experimental conditions. These in vitro studies provide new evidence for roles for Type I and II mGlu receptors in viscerosensory processing in nucleus tractus solitarii.