RESTORATION OF EXTENSOR EXCITABILITY IN THE ACUTE SPINAL CAT BY THE 5-HT2 AGONIST DOI

1. The decerebrate cat preparation with an intact spinal cord is chara cterized by a high degree of excitability in extensor motoneuron pools , which is eliminated by acute spinalization. Subtype-specific agonist s for serotonin (5-HT) were investigated in terms of their effectivene ss in restoring the extensor excitability following spinalization. 2. Our hypothesis was that 5-HT2 receptors have the primary role in enhan cement of extensor reflex excitability, whereas 5-HT1A and 5-HT1B/D re ceptors are relatively unimportant. Reflex excitability was assessed f rom the tonic levels of force and electromyographic (EMG) output from the ankle extensors medial grastrocnemius (MG) and soleus (SOL), and f rom the reflex forces in both these muscles generated by ramp-and-hold stretches of MG. 3. Before spinal transection, MG and SOL usually exh ibited a small amount of tonic background EMG activity and force outpu t. Ramp-and-hold stretch of MG generated a large-amplitude reflex resp onse. Spinal transection at the level of T-10 virtually abolished toni c background activity in both extensors and greatly attenuated the MG stretch reflex. Ventral topical application of the selective 5-HT2A/2c agonist +/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochlor ide (DOI) restored the amplitude of the MC stretch reflex in a dose-de pendent fashion. However, a considerable portion of the DOI-mediated r estoration of MG stretch reflex force was due to elevation of tonic ba ckground force levels above previous intact cord levels. 4. The DOI-in duced increase in extensor tonic background excitability and facilitat ion of MG stretch reflex were reversed by ventral topical administrati on of the selective 5-HT2 antagonist ketanserin. No increase in extens or excitability was observed in spinalized preparations after administ ration of either the 5-HT1A agonist (+/-)-8-hydroxy-dipropylaminotetra lin hydrobromide or the 5-HT1B/1D agonist 7-trifluoromethyl-4-(4 methy l-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline maleate. These data strongl y suggest that the DOI-induced facilitation of extensor stretch reflex and tonic activity in spinalized preparations is mediated through an action on spinal 5-HT2 receptors. 5. One important difference between the actions of DOI in spinalized versus intact states was that the DOI -induced tonic and reflex forces in the spinalized state were subject to irregular oscillations. In contrast, DOI did not noticeably affect the smoothness of reflex force generation in the intact state. This di screpancy was probably due to the effects of clasp knife inhibition fr om muscular free nerve endings, which have potent reflex actions in th e spinalized but not intact states. Thus DOI elevated excitability lev els but did not alter the effects of spinalization on stretch reflex p atterns.