Inhibition of tryptophan hydroxylase abolishes fatigue induced by central tryptophan in exercising rats

<jats:p>Fatigue during prolonged exercise is related to brain monoamines concentrations, but the mechanisms underlying this relationship have not been fully elucidated. We investigated the effects of increased central tryptophan (<jats:styled-content style="fixed-case">TRP</jats:styled-content>) availability on physical performance and thermoregulation in running rats that were pretreated with parachlorophenylalanine (<jats:styled-content style="fixed-case">p</jats:styled-content>‐<jats:styled-content style="fixed-case">CPA</jats:styled-content>), an inhibitor of the conversion of <jats:styled-content style="fixed-case">TRP</jats:styled-content> to serotonin. On the 3 days before the experiment, adult male Wistar rats were treated with intraperitoneal (<jats:styled-content style="fixed-case">ip</jats:styled-content>) injections of saline or <jats:styled-content style="fixed-case">p</jats:styled-content>‐<jats:styled-content style="fixed-case">CPA</jats:styled-content>. On the day of the experiment, animals received intracerebroventricular (<jats:styled-content style="fixed-case">icv</jats:styled-content>) injections of either saline or <jats:styled-content style="fixed-case">TRP</jats:styled-content> (20.3 <jats:styled-content style="fixed-case">μM</jats:styled-content>) and underwent a submaximal exercise test until fatigue. Icv <jats:styled-content style="fixed-case">TRP</jats:styled-content>‐treated rats that received ip saline presented higher heat storage rate and a 69% reduction in time to fatigue compared with the control animals. Pretreatment with ip <jats:styled-content style="fixed-case">p</jats:styled-content>‐<jats:styled-content style="fixed-case">CPA</jats:styled-content> blocked the effects of <jats:styled-content style="fixed-case">TRP</jats:styled-content> on thermoregulation and performance. Moreover, <jats:styled-content style="fixed-case">ip p</jats:styled-content>‐<jats:styled-content style="fixed-case">CPA</jats:styled-content> administration accelerated cutaneous heat dissipation when compared with saline‐pretreated rats. We conclude that an elevated availability of central <jats:styled-content style="fixed-case">TRP</jats:styled-content> interferes with fatigue mechanisms of exercising rats. This response is modulated by serotonergic pathways, because <jats:styled-content style="fixed-case">TRP</jats:styled-content> effects were blocked in the presence of <jats:styled-content style="fixed-case">p</jats:styled-content>‐<jats:styled-content style="fixed-case">CPA</jats:styled-content>. Our data also support that a depletion of brain serotonin facilitates heat loss mechanisms during exercise.</jats:p>