The noradrenergic cell groups provide neural inputs to almost all brain areas including the respiratory network. Developmental dysfunctions in these neurons are linked to pathological conditions such as Rett syndrome and Sudden Infant Death, which can impair the control of the cardio-respiratory system and coordination of the sleep-waking cycle. We have been evaluating the involvement of A5 and A6 (locus coeruleus – LC) cell groups in the cardiorespiratory response to central (7-10% CO2 in air) and peripheral (7-10% O2) chemoreflex stimulation. A reduction of approximately 80% of noradrenergic (NA) neurons of LC is associated with a large decrease in the respiratory response to CO2 of approximately 64%, indicating that this nucleus exerts a profound effect on the CO2-drive to breathe, but no effect is observed during low O2 conditions (Biancardi et al., 2008; 2010). These data suggests the specific role of LC NA neurons in the ventilatory response to high CO2 rather than to hypoxia. Many neurotransmitters/neuromodulators have been demonstrated to be involved in the modulation of the LC response, such as serotonin, orexin, glutamate, ATP and also the GAP junctions (Gargaglioni et al., 2010). As to cardiovascular response, chemical lesion of the LC with 6-hydroxydopamine (6-OHDA) does not affect mean arterial pressure and heart rate during normocapnia and hypercapnia, indicating that noradrenergic LC neurons are unlikely to play a significant role in the control blood pressure and heart rate. However, lesion of LC using substance P-saporin conjugate (SP-SAP), that kills NK-1 immunoreactive (NK1R-ir) neurons, increase the heart rate during hypercapnia, suggesting that NK1R-ir neurons in the LC, probably the GABAergic ones, may modulate heart rate during CO2 exposure, since Glutamic Acid Decarboxylase immunoreactivity decreases after SP-SAP lesion (de Carvalho et al., 2010). Regarding A5 region, the role of this NA group in central and peripheral chemoreflex is strongly dependent on the state of the animal, anesthetized or unanesthetized. In unanesthetized animals, A5 noradrenergic neurons exert an excitatory modulation on the ventilatory response to hypoxia but do not affect cardiorespiratory control during CO2 exposure. However, in urethane-anesthetized animals, A5 noradrenergic neurons contribute to the sympathoexcitation and the increase in phrenic nerve activity produced by raising the end-expiratory CO2 (Taxini et al., 2011). In addition, under anesthesia, these noradrenergic neurons are not involved in autonomic regulation elicited by peripheral chemoreflex activation.