SPINAL 5-HT-RECEPTORS AND TONIC MODULATION OF TRANSMISSION THROUGH A WITHDRAWAL REFLEX PATHWAY IN THE DECEREBRATED RABBIT

1 In decerebrated, non-spinalized rabbits, intrathecal administration of either of the selective 5-HT1A-receptor antagonists (S)WAY-100135 o r WAY-100635 resulted in dose-dependent enhancement of the reflex resp onses of gastrocnemius motoneurones evoked by electrical stimulation o f all myelinated afferents of the sural nerve. The approximate ED(50) for WAY-100635 was 0.9 nmol and that for (S)WAY-100135 13 nmol. Intrat hecal doses of the antagonists which caused maximal facilitation of re flexes in non-spinalized rabbits had no effect in spinalized preparati ons. 2 In non-spinalized animals, intravenous administration of (S)WAY -100135 was significantly less effective in enhancing reflexes than wh en it was given by the intrathecal route. 3 When given intrathecally, the selective 5-HT2A/2C-receptor antagonist, ICI 170,809, produced a b ell-shaped dose-effect curve, augmenting reflexes at low doses (less t han or equal to 44 nmol), but reducing them at higher doses (982 nmol) . Idazoxan, the selective alpha(2)-adrenoceptor antagonist, was less e ffective in enhancing reflex responses when given intrathecally after ICI 170,809 compared to when it was given alone. Intravenous ICI 170,8 09 resulted only in enhancement of reflexes and the facilitatory effec ts of subsequent intrathecal administration of idazoxan were not compr omised. 4 The selective 5-HT4-receptor blocker ondansetron faciliated gastrocnemius medialis reflex responses in a dose-related manner when given by either intrathecal or intravenous routes. This drug was sligh tly more potent when given i.v. and it did not alter the efficacy of s ubsequent intrathecal administration of idazoxan. 5 None of the antago nists had any consistent effects on arterial blood pressure or heart r ate. 6 These data are consistent with the idea that, in the decerebrat ed rabbit, 5-HT released from descending axons has multiple roles in c ontrolling transmission through the sural-gastrocnemius medialis refle x pathway. Thus, it appears 5-HT tonically inhibits transmission betwe en sural nerve afferents and gastrocnemius motoneurones by an action a t spinal 5-HT1A-receptors. Spinal 5-HT2A/2C-receptors may mediate a we ak inhibition of transmission in the spinal cord, but more convincing evidence was obtained for their involvement in descending facilitatory tone. Further, some of the facilitatory consequences of spinal alpha( 2)-adrenoceptor blockade may be mediated through 5-HT2 type receptors. Spinal 5-HT3 receptors do not appear to have a major role in tonic mo dulation of the sural-gastrocnemius medialis reflex.