Substance P‐saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity

All medullary central chemoreceptor sites contain neurokinin‐1 receptor immunoreactivity (NK1R‐ir). We ask if NK1R‐ir neurons and processes are involved in chemoreception. At one site, the retrotrapezoid nucleus/parapyramidal region (RTN/Ppy), we injected a substance P‐saporin conjugate (SP‐SAP; 0.1 pmol in 100 nl) to kill NK1R‐ir neurons specifically, or SAP alone as a control. We made measurements for 15 days after the injections in two groups of rats. In group 1, with unilateral injections made in the awake state via a pre‐implanted guide cannula, we compared responses within rats using initial baseline data. In group 2, with bilateral injections made under anaesthesia at surgery, we compared responses between SP‐SAP‐ and SAP‐treated rats. SP‐SAP treatment reduced the volume of the RTN/Ppy region that contained NK1R‐ir neuronal somata and processes by 44 % (group 1) and by 47 and 40 % on each side, respectively (group 2). Ventilation (V̇E) and tidal volume (VT) were decreased during air breathing in sleep and wakefulness (group 2; P < 0.001; two‐way ANOVA) and Pa,CO2 was increased (group 2; P < 0.05; Student's t test). When rats breathed an air mixture containing 7 % CO2 during sleep and wakefulness, V̇E and VT were lower (groups 1 and 2; P < 0.001; ANOVA) and the ΔV̇E in air containing 7 % CO2 compared to air was decreased by 28‐30 % (group 1) and 17‐22 % (group 2). SP‐SAP‐treated rats also slept less during air breathing. We conclude that neurons with NK1R‐ir somata or processes in the RTN/Ppy region are either chemosensitive or they modulate chemosensitivity. They also provide a tonic drive to breathe and may affect arousal.

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