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

The effects of the 5-HT(1B/1D) receptor agonist L-741,604 on a trigeminally-mediated (jaw depressor) reflex and a spinally-mediated (flexion withdrawal) reflex have been compared between spinalized and intact, anaesthetized rabbits. 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 micromol kg(-1) i.v. This effect was reversed by the 5-HT(1B/1D) antagonist GR 127,935 (1 - 2 micromol kg(-1) i.v.). 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. In spinalized rabbits, L-741,604 up to 0.3 micromol 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 micromol 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. L-741,604 increased arterial blood pressure and decreased heart rate in both preparations, effects that were reversed by GR 127,935. 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-HT(1B/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.