Development of degenerative muscle weakness by chronic administration of beta,beta'-iminodipropionitrile in the drinking water to rats: a model for motorneuropathy.
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.
Kitahara
Y
Y
Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
Maki
T
T
Torii
K
K
D000818:Animals; D004195:Disease Models, Animal; D004326:Drinking; D008297:Male; D016472:Motor Neuron Disease / Q000139:chemically induced* / Q000473:pathology; D018908:Muscle Weakness / Q000139:chemically induced* / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009133:Muscular Atrophy / Q000139:chemically induced; D009498:Neurotoxins / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009498:Neurotoxins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile