To determine whether EEG synchronization in sleep has a metabolic equivalent, we investigated state-dependent changes in extracellular concentrations of amino acids. In vivo microdialysis studies were performed in the ventroposterolateral (VPL) nuclei of the thalamus of cats during natural slow wave sleep (SWS), waking (W) and carbachol-induced paradoxical sleep (PS) like episodes. About two-fold increases in aspartate, glutamate, asparagine, glycine, alanine and gamma-aminobutyric acid (GABA) were observed in SWS compared with control samples collected in W, but serine increased to 487 +/- 211%. In the PS-like state, glutamine increased and GABA decreased. These results suggest changes in intracellular processes reflected by amino acid release in the thalamus, specific to slow wave generation in EEG during natural sleep.