The effect of dantrolene sodium on the discharge of alpha and gamma motoneurones to the soleus muscle in the decerebrate rat

Abstract

The effects of intravenous infusion of the direct acting muscle relaxant, dantrolene sodium (5 mg kg−1), on tension, integrated EMG, soleus muscle motor unit discharge frequency and gamma nerve fibre discharge were measured in the decerebrate rat. Dantrolene sodium did not have any detectable direct effect upon the discharge of the gamma nerve fibres. The soleus muscle of the decerebrate preparations exhibited spontaneous tension and reflex responses. With the muscle held at constant length, dantrolene sodium caused an increase in the integrated EMG in 15 out of 18 experiments and a decrease in muscle tension in 15 out of 17. The results from these experiments showed great variability. Dantrolene sodium caused a slight reduction in the tension response to tonic stretch; this was accompanied by an increase in the integrated EMG. Dantrolene sodium also caused a shift in the relationship between tension and integrated EMG during the phasic component of the stretch reflex, with a greater integrated EMG being associated with a reduced tension. Motor unit discharge frequencies were found to increase but not sufficiently to overcome the action of dantrolene sodium. It is concluded that motor unit recruitment must play an important role in the compensation for the muscle weakening action of dantrolene sodium.

Dantrolene diminishes forelimb force-related tremor at doses that do not decrease operant beahvior in the rat.

“…The fact that dantrolene altered the relationship between isometric force output and force-related tremor at all doses tested demonstrates that in healthy animals the drug's effects on the activity of motor unit ensembles may be present at doses below those that produce measurable force dampening effects. This is contrary to the hypothesis that increased EMG activity compensates for the muscle-weakening effect of dantrolene (Farquhar & Part, 1988). However, in the current study, animals emitted isometric forces that were well below their maximum force production in this task.…”

“…Although the effects of dantrolene on isometric force output were modest (a 12% decrease in Hold force at the 10 mg/kg dose) but significant, its tremor dampening effects were more robust (a 35% decrease at the highest dose). These effects were not expected on the basis of previous findings suggesting that dantrolene increases EMG measures while decreasing muscle tension (Farquhar & Part, 1988).…”

The effect of EU4093 (azumolene sodium) on the contraction of intrafusal muscle in the soleus muscle of the anaesthetized rat

“…However, this is not a possibility with EU4093 because this drug still has an effect on intrafusal contraction at a stimulation frequency of 200s '. In the decerebrate rat, dantrolene sodium does not have any effect upon the discharge of gamma nerve fibres to the de-afferented soleus muscle (Farquhar & Part, 1988). Hence in this preparation, at least, the nervous system is not compensating for the action of dantrolene sodium on intrafusal muscle and so the fact that EU4093 has a s 11 .1.…”

“…At present there are no data on the effect of EU4093 on the tetanic contraction of extrafusal muscle in the anaesthetized rat. However in the anaesthetized and decerebrate rat the nervous system compensates for the effect of dantrolene sodium (Farquhar et al, 1986;Farquhar & Part, 1988) only to a limited extent by increasing the frequency of discharge of the alpha motoneurones; more important are recruitment of additional motor units and modification of the patterns of discharge. It is possible therefore that dantrolene sodium and EU4093 would have a similar muscle relaxant action in the intact animal even if the effect of EU4093 on extrafusal muscle had a similar frequency dependency as that on intrafusal muscle.…”

Clinical Pharmacology of Motor Neurons

“…This action is more marked in the musele fibres of fast-than of slow-twiteh motor units (Jami et al 1983;Everts and Van Hardeveld 1987). No direet effeet on the diseharge of gamma nerve fibres to the soleus musele was found in the deeerebrate rat nor is there evidenee of a direet action on alpha motoneuron diseharge rate (Farquhar and Part 1988). The inhibitory effeet of dantrolene on the musele eelI is markedly redueed when the stimulus frequeney is inereased so that fused tetanic eontraetions are less inhibited than subtetanic and twiteh eontraetions (Ellis and Bryant 1972;Leslie and Part 1981).…”