Previous electrophysiological experiments have shown that brain noradrenaline neurons in the locus ceruleus are activated by thermal cutaneous stimuli. In the present study a putative involvement of excitatory amino acids (EAA) in cutaneous LC activation was analyzed. Intraventricular administration of kynurenic acid (1 mumol), a broad spectrum EAA antagonist, or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 0.1 mumol) as well as subcutaneous administration of the specific NMDA antagonist MK 801 (2 mg/kg) almost totally abolished the response of LC neurons to both non-noxious and noxious cutaneous sensory stimuli. We propose that the activation of LC neurons following thermal cutaneous stimuli is mediated via release of EAA from nerve terminals emanating from nucleus paragigantocellularis (PGi).