By coupling glutamate to the IP3 signaling pathway, group I metabotropic receptors can increase intracellular Ca2+ concentration, and might thus contribute to excitotoxicity. To identify neurons that might be vulnerable to such injury, we performed immunofluorescence histochemistry for metabotropic glutamate receptor 1 alpha (mGluR1 alpha) in the cerebral cortex of adult rat. mGluR1 alpha was in somata and dendrites of a subset of non-pyramidal neurons scattered throughout the cerebral cortex. To further characterize mGluR1 alpha-positive neurons, we investigated its colocalization with several neurochemical markers. Nearly all mGluR1 alpha-positive cells were interneurons immunopositive for gamma-aminobutyric acid. The majority (70-80%) of mGluR1 alpha-immunopositive neurons were double-labeled for somatostatin. Approximately half of calretinin-positive neurons and 30% of calbindin-positive neurons expressed mGluR1 alpha. In contrast, parvalbumin-expressing neurons were rarely positive for mGluR1 alpha. Neurons staining strongly for mGluR1 alpha were also positive for GluR1. These results indicated that mGluR1 alpha is expressed by specific classes of GABAergic neurons in the neocortex, and suggests a mechanism by which these neurons may be especially vulnerable to excitotoxic injury. (C) 2000 Elsevier Science B.V. All rights reserved.