Progressive
muscle weakness accompanied by progressive
muscle atrophy was investigated in rats administered
beta,beta'-iminodipropionitrile (IDPN) chronically in the
drinking water. Spontaneous running wheel activity declined slowly and reached a constant low level before postural
muscle weakness was apparent. The rats being offered IDPN in the
drinking water showed definite postural
muscle weakness about 25 weeks after first being given IDPN, and muscle strength declined gradually throughout the remainder of the experiment (to 66 weeks). Flaccid
paralysis became apparent in the hind limbs in the later stages of the experiment. Neurogenic
muscle atrophy, measured by group
atrophy of the muscle fibers, also progressed slowly, almost in parallel with the loss of muscle strength. At the end of the experiment, muscle weight of the gastrocnemius had decreased to about 20% that of control [F(2, 12) = 40.4, p < 0.05]. Plasma
creatinine in the rats given IDPN in the
drinking water for 66 weeks was significantly elevated over that of controls [F(2, 12) = 20.1, p < 0.05]. On the other hand, in rats given IDPN intraperitoneally, postural
muscle weakness and
muscle atrophy were less apparent, and plasma
creatinine was normal. However, in these animals, abnormal behaviors, such as hyperexcitement, circling, and
choreic movement (ECC syndrome), were apparent. These results suggest that the present model, which administers IDPN chronically in the
drinking water ad lib and does not show
involuntary movements and ECC syndrome, is of potential importance for investigation of
chronic diseases of progressive
muscle weakness with progressive
muscle atrophy, and for assessing the efficacy of drugs and
therapies for treating chronic
neuromuscular diseases.