restoration of extensor excitability in the Acute spinal cat by the 5-ht 2
Agonist doi.
Miller, J.F., K.D. Paul, R.H. Lee, W.Z. Rymer and C.J. Heckman.
Department of Physiology, Northwestern University School of Medicine,
Chicago, IL 60611.
APStracts 2:0289N, 1995.
SUMMARY AND CONCLUSIONS
1. The decerebrate cat preparation with an intact spinal cord is characterized
by a high degree of excitability in extensor motoneurons pools, which is
eliminated by acute spinalization. Sub-type specific agonists for serotonin
(5-HT) were investigated in terms of their effectiveness in restoring the
extensor excitability following spinalization. 2. Our hypothesis was that 5-HT
2 receptors have the primary role in enhancement of extensor reflex
excitability, while 5-HT 1A and 5-HT 1B/D receptors are relatively
unimportant. Reflex excitability was assessed from the tonic levels of force
and EMG output from the ankle extensors medial gastrocnemius (MG) and soleus
(SOL) and from the reflex forces in both these muscles generated by ramp and
hold stretches of the MG. 3. Prior to spinal transection, MG and SOL usually
exhibited a small amount of tonic background EMG activity and force output.
Ramp and hold stretch of the MG generated a large amplitude reflex response.
Spinal transection at the level of T10 virtually abolished tonic background
activity in both extensors and greatly attenuated the MG stretch reflex.
Ventral topical application of the selective 5-HT 2A/2C agonist DOI restored
the amplitude of the MG stretch reflex in a dose-dependent fashion. However, a
considerable portion of the DOI-mediated restoration of MG stretch reflex
force was due to elevation of tonic background force levels above previous
intact cord levels. 4. The DOI-induced increase in extensor tonic background
excitability and facilitation of MG stretch reflex were reversed by ventral
topical administration of the selective 5-HT 2 antagonist ketanserin. No
increase in extensor excitability was observed in spinalized preparations
after administration of either the 5-HT 1A agonist 8-OH-DPAT or the 5-HT 1B/1D
agonist CGS-12066B. These data strongly suggest that the DOI-induced
facilitation of extensor stretch reflex and tonic activity in spinalized
preparations is mediated through an action on spinal 5-HT 2 receptors. 5. One
important difference between the actions of DOI in spinalized vs. 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 discrepancy was probably due to the effects of clasp knife
inhibition from muscular free nerve endings, which have potent reflex actions
in the spinalized but not intact states. Thus DOI elevated excitability levels
but did not alter the effects of spinalization on stretch reflex patterns.
Received 17 March 1995; accepted in final form 14 September 1995.
APS Manuscript Number J177-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95