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

Abstract

A behavioral preparation that affords concurrent measurement of forelimb force and tremor in rats was used to assess the effects of dantrolene sodium, a muscle relaxant and potential neuroprotective drug. Rats that were trained to press downward on an isometric force transducer while simultaneously licking water reinforcement were administered dantrolene (5.0 mg/kg, 7.5 mg/kg, and 10.0 mg/kg). Dantrolene diminished force output at the 7.5 mg/kg and 10.0 mg/kg doses and decreased tremor at all three doses. Dantrolene decreased the ratio of forelimb tremor to force output at all three doses. Dantrolene did not suppress operant behavioral output at these doses. These results suggest that dantrolene may affect fine motor control and decrease tremor at doses that do not produce behavioral suppression.

Young and middle-aged rats exhibit isometric forelimb force control deficits in a model of early-stage Parkinson's disease

“…Behavioral training and experimental sessions were conducted in modified operant chambers that were enclosed in individual sound-attenuating cubicles as previously described [14, 45]. In each chamber, a cylindrical recess provided access to the 0.5 ml cup of a solenoid-operated dipper.…”

“…The goal of the current study was to determine whether partial unilateral nigrostriatal DA depletion affects isometric force control in rats in a manner similar to the effects of early-stage PD in humans. Rats were trained to produce sustained press-hold-release forelimb responses that allowed for analyses of force output and spectral analysis of stability and tremor [45, 48]. Although the effects of DA-blocking drugs have been measured in this task [13, 14, 42], the effects of nigrostriatal DA depletion on isometric force control have not been assessed in a model of PD.…”

Forelimb Resistance Exercise Protects Against Neuromuscular Junction Denervation in the SOD1-G93A Rat Model of ALS

“…We then calculated force-related tremor (integrated power) by summing the area in the power spectrum between the 10–25 Hz frequency band, as determined by Fourier analysis of the 3.36 s stationary component of the force-time waveforms, as in our previous studies. 16 , 17 The ratio of tremor to force output was also calculated to normalize these two related variables as we have found this measure to decrease with repeated resistance exercise. 18 …”

“…Rats were bred in our colony and genotyped by Transnetyx. At approximately 2 months of age, rats were gradually water restricted and placed in modified Gerbrands operant chambers for training (chambers are described in detail in 16,17). It should be noted that all rats received sufficient water to avoid dehydration (per our animal protocol) and maintain weight gain throughout the experiment until SOD1-G93A rats exhibited disease-related weight loss.…”