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 1 27,935 had no significant effects on reflexes evoked in medial gastrocnemiu s 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 mu mol cumulative) routes. 2 In decerebrated, spinalized rabbits, intrathecal GR 127,935 in doses of u p to 543 nmol, had no effect on the sural-gastrocnemius reflex. Furthermore , this drug failed to alter enhancement of the sural-gastrocnemius reflex i nduced 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 ago nists 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-gastroc nemius reflex to increase to 140% of pre-drug levels, and arterial blood pr essure to rise by about 10 mmHg. Subsequent administration of GR 127,935 at 0.9-1.8 mu mol kg(-1) reversed the presser effect of the agonists but not the increase in reflexes. The 5-HT1A receptor antagonist WAY-100,635 (185 n mol 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 mu mol kg(-1) i.v.) restored re flexes to pre-drug control values after L-741,604 (it was not tested agains t L-694,247). 4 These data indicate that 5-HT1B/1D receptors do not significantly modulat e transmission in the sural-gastrocnemius reflex pathway, and that the enha ncement of reflexes by 8-OH-DPAT and L-741,604 is probably mediated by 5-HT 7 receptors.