The effect of metabotropic glutamate receptor (mGluR) agonists and antagonists on the spinal cord network underlying locomotion in the lamprey has been analysed. The specific group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) and the broad-spectrum mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) both increased the burst frequency of N-methyl-d-aspartic acid (NMDA)-induced fictive locomotion and depolarized grey matter neurons. The burst frequency increase induced by the mGluR agonists was counteracted by the mGluR antagonists (+)-alpha-methyl-4-carboxyphenylglycine
((+)-MCPG), cyclopropan[b]chromen-1a-carboxylic acid ethylester (CPCCOEt) and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA). Application of CPCCOEt alone reduced the locomotor burst frequency, indicating that mGluRs are endogenously activated during fictive locomotion. The mGluR antagonist CPCCOEt had no effect on NMDA-, or (S)-α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA)-induced depolarizations. The mGluR agonists 1S,3R-ACPD and DHPG increased the amplitude of NMDA-induced depolarizations, a mechanism which could account for the increase in burst frequency. The group III mGluR agonist L-2-amino-4-phosphonobutyric acid reduced intraspinal synaptic transmission and burst frequency.