Effect of 8-OH DPAT and ketanserin on the ventilatory acclimatization to hypoxia in awake goats

We have previously reported that broad-spectrum serotonergic blockade increased the acute hypoxic ventilatory response in awake goats. The purpose of the present study was to examine the putative serotonin (5-HT) receptor subtype(s) that may have contributed to this response. Following the administration of the selective 5-HT_1A-receptor agonist, 8-hydroxy-(2-di-n-propylamino) tetralin (8-OH DPAT, 0.1 mg·kg^-1 i.v.), there was an increase in normoxic expired minute ventilation (V̇E) that was due to an increased breathing frequency. V̇E increased during hypoxia but the change in V̇E (ΔV̇E) associated with hypoxic exposure was not different from the ΔV̇E of saline treated goats. The combination of 8-OH DPAT and a selective 5-HT_2A/2C receptor antagonist, ketanserin (0.1 and 1.0 mg·kg^-1 i.v., respectively), also increased normoxic V̇E but did not alter the hypoxia induced ΔV̇E. Both 8-OH DPAT alone and in combination with ketanserin attenuated the change in V̇E associated with sustained hypoxia but neither was able to attenuate the increased hypoxic ventilatory response that occurs following acclimatization. The augmented acute hypoxic ventilatory response that we previously reported does not appear to be mediated via the activation of the 5-HT_1A receptor or through the combination of 5-HT_1A activation and 5-HT_2A/2C blockade. The results of this study further suggest that while 5-HT may modulate hypoxic ventilation it does not appear to be necessary for the development of ventilatory acclimatization to hypoxia.