Effect of 5-HT A receptor agonist, 8-OH-DPAT, on cough responses in the conscious guinea-pig

Abstract

We have studied the role for 5-hydroxytryptamine (5-HT) in the modulation of the cough reflex by examining the effect of a selective 5-HT 1A receptor agonist, 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT) on cough and respiratory rate in conscious guinea pigs. Animals were placed in a box and exposed to the tussive agent citric acid (0.5 M) for 10 min, 3 min after terbutaline (0.05 mg/kg i.p.) was administered to prevent bronchoconstriction. 8-OH-DPAT inhibited at low doses (0.008 and 0.016 mg/kg) but potentiated at high doses (0.25 and 0.5 mg/kg) the citric acid-induced number of coughs, but dose-dependently increased respiratory rate. Methysergide (0.05–5 mg/kg), a 5HT 1 and 5HT 2 receptor antagonist, and ketanserin (0.05 mg/kg), a 5HT 2 receptor antagonist, had no effects on cough or respiratory rate. Methysergide inhibited the increased cough responses and respiratory rate induced by 8-OH-DPAT at high doses, while ketanserin was without effect. These results suggest that 8-OH-DPAT may induce both an inhibition and activation of the cough reflex, the latter involving central 5HT 1-receptor activation.