Effects of a selective 5-HT1B/1D receptor agonist on spinal and trigeminal reflexes in the anaesthetized rabbit

1 The effects of the 5-HT1B/1D receptor agonist L-741,604 on a trigeminally-mediated (law depressor) reflex and a spinally-mediated (flexion withdrawal) reflex have been compared between spinalized and intact, anaesthetized rabbits. 2 L-741,604 depressed the jaw depressor reflex dose-dependently in all animals, to a median of 5% (inter-quartile range, IQR, 3-28%, n=18) of pre-drug levels after a cumulative dose of 3.1 mu mol kg(-1) i.v. This effect was reversed by the 5-HT1B/1D antagonist GR 127,935 (1-2 mu mol kg(-1) i.v.). 3 The flexion withdrawal reflex was depressed by L-741,604 in non-spinalized animals, to a median of 22% (IQR 10-36%, n = 10) of pre-drug levels after the highest dose, an action that was reversed by GR 127,935. 4 In spinalized rabbits, L-741,604 up to 0.3 mu mol kg(-1) i.v. cumulative increased the flexion reflex to a median of 189% (IQR 169-198%, n = 8) of pre-drug controls. With higher doses the reflex decreased, so that after 3.1 mu mol kg(-1) it was 75% (IQR 55-96%) of pre-drug levels. Subsequent GR 127,935 increased reflexes to a median of 180% (IQR 136-219%) of controls. 5 L-741,604 increased arterial blood pressure and decreased heart rate in both preparations, effects that were reversed by GR 127,935. 6 Thus, when the spinal cord was intact L-741,604 inhibited spinal and trigeminal reflexes in the same way. Although spinalization enabled a non-5-HT1B/1D-mediated excitatory effect of L-741,604 on spinal reflexes, there was a clear inhibitory effect of the drug at high doses. These data suggest that L-741,604 inhibits spinal reflexes by increasing descending inhibition and by a direct action in the cord. The same processes could apply to inhibition of trigeminally-mediated events.