Genetically Selected High Capacity Runners Have Altered Serotonergic and Dopaminergic Receptor mRNA in the Brain

Abstract

Although adaptations in peripheral systems such as liver function and skeletal muscle composition can contribute to ones capacity to sustain aerobic activity, central neural circuits regulating fatigue may also play a critical role. We evaluated possible differences in central fatigue pathways, including the serotonergic (5-HT) and dopaminergic (DA) systems, between two contrasting rat-lines selectively bred for endurance treadmill running capacity. The lines were designated as Low Capacity Runners (LCR) and High Capacity Runners (HCR). Using in situ hybridization, we examined baseline differences in central serotonergic (5-HT transporter, 5-HT1A, 5-HT1B) and dopaminergic (DR-D1, DR-D2) receptor mRNA in LCR versus HCR. Rats were tested on a treadmill 3 weeks prior to sacrifice to verify trait differences. HCR ran 2 times faster,10 times farther, and 5 times longer than the LCR. Interestingly, HCR had higher levels of 5-HT1B mRNA in the dorsal and median raphe nuclei relative to LCR, but similar levels of 5-HT transporter and 5-HT1A mRNA in these areas. Furthermore, HCR expressed higher levels of DR-D2 mRNA than LCR in only the rostral-mid nucleus accumbens, but not other levels of the nucleus accumbens or caudate putamen. There was no difference in DR-D1 mRNA levels in the nucleus accumbens or caudate putamen between HCR and LCR. These data suggest that constraint of the central serotonergic and dopaminergic responses, via 5-HT1B and DR-D2 inhibitory autoreceptors, during exercise may be involved in the mechanisms by which HCR have delayed onset of fatigue.