Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level.
The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.
Tanii
H
H
Department of Neuropsychiatry, Osaka University Medical School, Japan. tanii@psy.med.osaka.u.ac.jp
Taniguchi
N
N
Niigawa
H
H
Hosono
T
T
Ikura
Y
Y
Sakamoto
S
S
Kudo
T
T
Nishimura
T
T
Takeda
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D001285:Atropine / Q000633:toxicity*; D001833:Body Temperature Regulation / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000633:toxicity*; D003402:Creatine Kinase / Q000097:blood; D003620:Dantrolene / Q000627:therapeutic use; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000633:toxicity*; D004576:Electromyography / Q000187:drug effects; D006220:Haloperidol / Q000633:toxicity*; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D009125:Muscle Relaxants, Central / Q000627:therapeutic use; D009127:Muscle Rigidity / Q000139:chemically induced; D009459:Neuroleptic Malignant Syndrome / Q000209:etiology*; D011817:Rabbits
D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists; D018492:Dopamine Antagonists; D009125:Muscle Relaxants, Central; D001285:Atropine; D003402:Creatine Kinase; D003620:Dantrolene; D006220:Haloperidol