On the role of 5-HT1B/1D receptors in modulating transmission in a spinal reflex pathway in the decerebrated rabbit.

1. In decerebrated rabbits, the selective 5-HT1B/1D receptor antagonist GR 127,935 had no significant effects on reflexes evoked in medial gastrocnemius motoneurones by electrical stimulation of the sural nerve, or on arterial blood pressure or heart rate when given by the intrathecal (up to 543 nmol cumulative) or intravenous (up to 1.8 micromol cumulative) routes. 2. In decerebrated, spinalized rabbits, intrathecal GR 127,935 in doses of up to 543 nmol, had no effect on the sural-gastrocnemius reflex. Furthermore, this drug failed to alter enhancement of the sural-gastrocnemius reflex induced by 8-hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), given at 300 nmol kg-1 i.v. 3. In decerebrated, spinalized rabbits, the selective 5-HT1B/1D receptor agonists L-694,247 (cumulative doses of 2 - 243 nmol kg-1 i.v.) and L-741,604 (cumulative doses of 3 - 307 nmol kg-1 i.v.), each caused the sural-gastrocnemius reflex to increase to 140% of pre-drug levels, and arterial blood pressure to rise by about 10 mmHg. Subsequent administration of GR 127,935 at 0.9 - 1.8 micromol kg-1 reversed the pressor effect of the agonists but not the increase in reflexes. The 5-HT1A receptor antagonist WAY-100,635 (185 nmol kg-1 i.v.) also failed to reverse the increase in reflexes, but the 5-HT1B/1D/5-HT2/5-HT7 ligand ritanserin (1.6 micromol kg-1 i.v.) restored reflexes to pre-drug control values after L-741,604 (it was not tested against L-694,247). 4. These data indicate that 5-HT1B/1D receptors do not significantly modulate transmission in the sural-gastrocnemius reflex pathway, and that the enhancement of reflexes by 8-OH-DPAT and L-741,604 is probably mediated by 5-HT7 receptors.