Acute selective serotonin-reuptake inhibition elevates basal ventilation and attenuates the rebreathing ventilatory response, independent of cerebral perfusion

Serotonin (5-HT) is integral to signaling in areas of the brainstem controlling ventilation and is involved in central chemoreception. Selective serotonin reuptake inhibitors (SSRIs), used to effectively increase 5-HT concentrations, are commonly prescribed for depression. The effects of SSRIs on the control of breathing and the potential influence of cerebral blood flow (CBF) have not been directly assessed. We hypothesized that a single SSRI dose in healthy adults would not impact resting ventilation, global CBF, or brainstem blood flow reactivity to CO2 but would steepen the slope of the hypercapnic ventilatory response (HCVR). In 15 young, healthy adults (6 females, 25 +/- 5 yr, 70 +/- 10 kg, 172 +/- 15 cm, 24 +/- 4 kg/cm(2)), using a placebo-controlled, double-blind, randomized design, we assessed baseline cardiorespiratory and CBF (duplex ultrasound) responses to SSRI (40 mg citalopram), as well as to hyperoxic hypercapnic rebreathing (as an index of central chemoreception). Baseline measures of mean arterial pressure, heart rate, minute ventilation, CBF, and the pressures of end-tidal oxygen and carbon dioxide were all not influenced by SSRI. Likewise, the sum of blood flowing through both vertebral arteries (as an index of brainstem blood flow) during hypercapnia was also unchanged. In contrast, basal ventilation (during rebreathing following hyperventilation and during hyperoxia) was elevated from 9.5 +/- 4.1 to 11.5 +/- 5.5 L/min (interaction P = 0.023); and counter to our hypothesis, the central chemoreceptor-mediated ventilatory response to CO2 was reduced following SSRI from 7.5 +/- 5.3 to 5.1 +/- 4.1 L/min/mmHg (interaction P = 0.027). The implications of these findings in health and pathology remain to be determined. NEW & NOTEWORTHY Acute inhibition of serotonin reuptake with citalopram diminishes the ventilatory response to hyperoxic hypercapnic rebreathing, possibly indicating decreased sensitivity of the central chemoreceptors and respiratory control centers. Additionally, ventilation during minimal chemoreceptor activation-i.e., following hypocapnia during hyperoxia-is elevated, perhaps signifying an increased tonic activity of the respiratory control areas. These changes appear to be independent of brainstem blood flow. These findings may have implications for antidepressant drug use.