Species differences in respiratory rhythm generation in rodents

We examined the role of riluzole (RIL)- and flufenamic acid (FFA)-sensitive mechanisms in respiratory rhythmogenesis in rats and hamsters using the in situ arterially perfused preparation. Based on the hypothesis that respiratory networks in animals capable of autoresuscitation would have a greater prevalence of membrane mechanisms that promote endogenous bursting, we predicted that older (weaned) hamsters (a hibernating species) would be more sensitive to the blockade of RIL- and FFA-sensitive mechanisms than age-matched rats and that younger (preweaned) rats would behave more like hamsters. Consistent with this, we found that respiratory motor output in weaned hamsters [>21 days postnatal (P21)] was highly sensitive to RIL (0.2-20 muM), while in young rats (P12-14) it was less so (only affected at higher concentrations of RIL), and weaned rats were not affected at all. On the other hand, respiratory motor output was equally reduced by FFA (0.25-25 muM) in both young and weaned rats but was unaffected in weaned hamsters. Coapplication of RIL and FFA (RIL + FFA) produced greater inhibition of respiration in both young and weaned rats compared with either drug alone. In contrast, in weaned hamsters, FFA coapplication offset the inhibitory effect of RIL alone. Increasing respiratory drive with hypercapnia/acidosis ameliorated the respiratory inhibition produced by RIL + FFA in weaned rats but had no effect in young rats. Data from the present study indicate that respiratory rhythmogenesis in young rats is more dependent on excitatory RIL-sensitive and FFA-sensitive mechanisms than older rats and that fundamental differences exist in the respiratory rhythmogenic mechanisms between rats and hamsters.