Vagal nerve stimulation (VNS) is used as a treatment for Epilepsy and is currently under investigation as a treatment for depression (see [M.S. George, Z. Nahas, X. Li, F.A. Kozel, B. Anderson, K. Yamanaka, J.H. Chae, M.J. Foust, Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS), Semin. Clin. Neuropsychiatry 7 (2002) 293-304; M.S. George, A.J. Rush, H.A. Sackeim, L.B. Marangell, Vagus nerve stimulation (VNS): utility in neuropsychiatric disorders, Int. J. Neuropsychopharmacol. 6 (2003) 73-83] for reviews). The mechanism of action of VNS is not fully understood [E. Ben-Menachem, Vagus-nerve stimulation for the treatment of epilepsy, Lancet Neurol. 1 (2002) 477-482] despite numerous imaging investigations (see [E. Ben-Menachem, Vagus-nerve stimulation for the treatment of epilepsy, Lancet Neurol. 1 (2002) 477-482; M.S. George, Z. Nahas, X. Li, F.A. Kozel, B. Anderson, K. Yamanaka, J.H. Chae, M.J. Foust, Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS), Semin. Clin. Neuropsychiatry 7 (2002) 293-304; M.S. George, A.J. Rush, H.A. Sackeim, L.B. Marangell, Vagus nerve stimulation (VNS): utility in neuropsychiatric disorders, Int J Neuropsychopharmacol 6 (2003) 73-83; M.S. George, H.A. Sackeim, L.B. Marangell, M.M. Husain, Z. Nahas, S.H. Lisanby, J.C. Ballenger, A.J. Rush, Vagus nerve stimulation. A potential therapy for resistant depression? Psychiatr. Clin. North Am. 23 (2000) 757-783] for reviews). However, there is some evidence to suggest that the locus coeruleus may play a role modulating the effects of VNS. This study investigated the effects of VNS (0.3mA), of sufficient intensity to recruit the A and B fibre components of the vagus [D.M. Woodbury, J.W. Woodbury, Effects of vagal stimulation on experimentally induced seizures in rats, Epilepsia 31 (Suppl. 2) (1990) S7-S19], on the discharge rate of single neurons from the locus coeruleus. This study is the first to demonstrate a direct neuronal response from the locus coeruleus following acute challenge of VNS in the anaesthetised rat. The results of this study indicate that neuronal activity of the locus coeruleus is modulated by VNS. This pathway through the locus coeruleus may be significant for mediating the clinical effects of VNS.