Inhibition of chronic hindlimb flexion in rat: evidence for mediation by 5-hydroxytryptamine

Abstract

Prolonged high-intensity stimulation of the rat hindlimb produces a persistent unilateral flexion. 5-Hydroxytryptamine (5-HT) has been implicated in the modulation of spinal cord mechanisms. Electrical stimulation across the upper hindlimb was used to induce a persistent hindlimb flexion. The flexion was measured after stimulation and at 72 h, both before and after spinal transection at T 7. Transection of the spinal cord typically resulted in an increase in flexion of 3–5 g (rebound). Pretreatment with para-chlorophenylalanine (pCPA) to deplete 5-HT, or the administration of metergoline, a non-specific 5-HT antagonist, had no significant effect on flexion at 72 h in the intact rat but abolished rebound. The 5-HT 1A agonist,(±)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (8-OH-DPAT) and 5-HT 1B agonist, m-trifluoromethylphenylpiperazine-HCl (TFMPP), had no effect on flexion at 72 h in the intact rat but reduced rebound. The 5-HT 2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-HCl (DOI), suppressed post-stimulation flexion and flexion subsequent to spinal section. Furthermore, ketanserin, a 5-HT 2 antagonist, restored flexion suppressed by DOI in the acutely spinalized rat. These results suggest that chronic hindlimb flexion is suppressed in the intact rat by descending, serotonergic fibers which exert an effect through spinal 5-HT 2 receptors. Moreover, 5-HT 1 agonist suppression of rebound implicates these receptors as well in the modulation of chronic hindlimb flexion.