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 complic ation 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 tempe rature, and high serum creatine phosphokinase (CPK) level. Administrat ion of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increas e in electromyographic activity with muscle rigidity similar to that o bserved in patients with NMS. Such rabbits also showed elevated body t emperature and serum CPK value. In addition to the similarity of the s igns and symptoms, all parameters measured (muscle rigidity, body temp erature, 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 NM S.