, 2008, Guyenet et al., 2010 and Nattie and Li, 2009). The retrotrapezoid nucleus (RTN), locus coeruleus, medullary raphe, hypothalamic orexinergic neurons and the NTS neurons are the main sites suggested to be involved with the central chemoreception (Abbott et al., 2009, Biancardi et al., 2008, Dean et al., 1989, Deng et al., 2007, Johnson et al., 2008, Moreira et al., 2007, Mulkey et al., 2004, Nattie

and Li, 2008, Richerson, 2004, Takakura et al., 2006 and Williams et al., 2007). The main focus of the present study is to reexamine the question whether the NTS, particularly the commissural buy Pictilisib division of the NTS caudal to the area postrema, is involved in chemoreception. Studies from the literature have suggested that acid-responsive neurons are located in the NTS and the acidification of the NTS region alters breathing (Dean et al., 1989 and Nattie and Li, 2008). Additionally, previous studies have tested the effects of the lesions or the glutamatergic blockade in the commNTS, suggesting Selleck Bcl-2 inhibitor that this region is essential for the cardiorespiratory responses to the peripheral chemoreceptor activation (Colombari et al., 1996, Sapru, 1996 and Braga

et al., 2007). On the other hand, a more recent study evaluated the effects of muscimol microdialysis in a more rostral portion of the commNTS, suggesting that the rostral portion of the commNTS is involved mainly with respiratory responses to hypercapnia (Nattie and Li, 2008). Based on the assumptions described above, in the present

study, also using muscimol injection to block the neuronal activity, we investigated the importance of the neurons located in a more caudal portion of the commNTS for the cardiorespiratory responses elicited by chemoreflex activation with hypoxia (8–10% O2 in the breathing air) or hypercapnia (8–10% Hydroxychloroquine purchase CO2 in the breathing air) in conscious or anesthetized rats. The experiments were performed on 36 male Holtzman rats weighing 300–330 g. The animals were housed individually in stainless steel cages in a room with controlled temperature (24 ± 2° C) and humidity (55 ± 10%). Lights were on from 7:00 am to 7:00 pm. Standard Guabi rat chow (Paulinia, SP, Brazil) and tap water were available ad libitum. The experimental protocols were approved by the Animal Experimentation Ethics Committee of the Institute of Biomedical Science of University of São Paulo. All efforts were made to minimize animal discomfort and the number of animals used. Rats were anesthetized with intraperitoneal (i.p.) injection of ketamine (80 mg/kg of body wt) combined with xylazine (7 mg/kg of body wt) and placed in a stereotaxic frame (model 1760; David Kopf Instruments). A stainless steel cannula was implanted into the commNTS using the coordinates: 15.0 mm caudal to bregma, in the midline and 7.5 mm below dura mater.