Hypertension and sympathetic overactivity observed after chronic exposure to intermittent hypoxia (CIH) in rats involve alterations in central coupling of respiratory and sympathetic activities. Here, we explored possible alterations in glutamatergic and purinergic mechanisms in the caudal aspect of nucleus of tractus solitarius (cNTS) as well as in the rostral aspect of ventrolateral medulla (rVLM) of juvenile rats submitted to CIH (6% of O2 every 9 min, 8 h/day, for 10 days) or maintained in normoxia (control). Rats of both groups were prepared for the working heart-brainstem preparation (Paton, 1996) by anaesthetizing with halothane until loss of paw withdrawal reflex and then bisecting sub-diaphragmatically. The animals were decerebrated at the precollicular level and phrenic (PN), central vagus (cVN), abdominal (Abd) and thoracic sympathetic nerves (tSN) were isolated and recorded. Glutamate microinjections (1, 3 and 10 mM; 20-30 nL) into the cNTS (caudal to calamus scriptorius) of CIH rats (n=10) evoked minor increase in cVN, no reductions in PN frequency and higher tSN excitation in comparison to control responses (n=8). These altered responses of CIH rats were accompanied by a significant increase of 10% in the density of NMDAR1 and GluR2/3 receptor subunities in the cNTS (P<0.05; CIH: n=7 vs control: n=7) evaluated by western-blot (WB). In relation to rVLM, microinjections of ATP (1, 10 and 50 mM; 20-30 nL) were performed in a region caudal to the facial nucleus, which contains mostly the pre-sympathetic neurons of rostral ventrolateral medulla and the Bötzinger respiratory neurons. We observed that tSN excitatory responses evoked by ATP were higher in CIH (n=8) than in control group (n=7), whilst no changes were observed in the magnitude of Abd excitatory and PN inhibitory responses. WB analysis showed an increase of approximately 20% in P2X3 and P2X4 receptor density (P<0.05; CIH: n=8 vs control: n=8) at the rVLM level of CIH rats. Together, pharmacological and WB data pointed out that glutamatergic and purinergic signaling are facilitated in dorsal and ventral medullary regions, respectively, of rats submitted to CIH. The contribution of these neurochemical mechanisms in the CIH-induced sympathetic and respiratory dysfunctions is matter for further investigation.