p-Chlorophenylalanine eliminates long-term modulation of the exercise ventilatory response in goats

Repeated hypercapnic exercise augments future exercise ventilatory responses, an effect termed long-term modulation. We hypothesized that serotonin depletion with p-chlorophenylalanine (PCPA, 100 mg  kg⁻¹ i.v.) would attenuate long-term modulation. Ventilation, CO₂ production and arterial blood gases were measured at rest and during exercise (4 km h⁻¹, 5% grade) in goats before and after training (14 hypercapnic exercise trials). Six post-training exercise trials were performed. Trials 1–3 and 4–6 were grouped for analysis (post-training 1 and 2, respectively). Without PCPA, training exaggerated the Pa_CO2 decrease from rest to exercise (pre-training: $\text{1.4±0.3}\text{mmHg}\text{;}$ post-training 1: $\text{3.1±0.3}\text{mmHg}\text{;}$ post-training 2: $\text{2.3±0.3}\text{mmHg}\text{; P<0.05),}$ indicative of long-term modulation. The Pa_CO2 decrease from rest to exercise was unaffected by training following PCPA (pre-training: $\text{1.4±0.1}\text{mmHg}\text{;}$ post-training 1: $\text{1.4±0.3}\text{mmHg}\text{;}$ post-training 2: $\text{1.1±0.5}\text{mmHg}\text{; P>0.05).}$ Thus, PCPA abolishes long-term modulation, implicating serotonin in its underlying mechanism.