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, 100mg kg(-1) i.v.) would attenuate long-term modulation. Ventilation, CO(2) production and arterial blood gases were measured at rest and during exercise (4kmh(-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(CO(2)) decrease from rest to exercise (pre-training: 1.4+/-3mmHg; post-training 1: 3.1+/-3mmHg; post-training 2: 2.3+/-3mmHg; P<0.05), indicative of long-term modulation. The Pa(CO(2)) decrease from rest to exercise was unaffected by training following PCPA (pre-training: 1.4+/-1mmHg; post-training 1: 1.4+/-3mmHg; post-training 2: 1.1+/-5mmHg; P>0.05). Thus, PCPA abolishes long-term modulation, implicating serotonin in its underlying mechanism.