Abstract

Background: We hypothesized that Nucleus Raphe Magnus (NRM) plays a role in the ventilatory and thermal responses to hypercapnia, and that its serotonergic neurons are involved in these responses. Methods: Non-specific lesions of NRM were performed microinjecting ibotenic acid (IBO, 0.4μg/0.2μL) in male Wistar rats. To study the role of NRM serotonergic neurons, rats received microinjections of anti-SERT-SAP (0.2pmol/0.2μL). Measurements of ventilation (VE, body plethysmography) and body temperature (Tb, biotelemetry) were performed in room air, followed by 60 or 120min of 7% CO2. Results: NMR non-specific lesions decreased the ventilatory response to CO2 [VE= 604.43±17.85 (IBO) vs 1275.10±17.64 mL kg-1min-1 (PBS); two-way ANOVA]. Lesions of NMR serotonergic neurons caused hypoventilation during air breathing [VE= 260.18± 45.52 mL kg-1min-1 (anti-SERT-SAP) vs 420.67±33.80 (anti-IgG-SAP, control group)] and a decreased ventilatory response to CO2 [VE= 558.69±64.58 (anti-SERT-SAP) vs 1167.83±68.91 mL kg-1min-1 (anti-IgG-SAP)]. The hypercapnia-induced hypothermia was not affected by lesions. Conclusion: NRM plays a key role in the ventilatory but not in the thermal response to hypercapnia, and serotonergic neurons of this nucleus contribute to a non-CO2 dependent chemical drive to breathe and are involved in the ventilatory response to CO2. Financial Support: FAPESP, CNPq, PROEX, USP.

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