Long-term treatment with clozapine on aging mice

To further clarify the relationship between central neurotransmitter systems, organ function and aging, we used mice to study the effects of long-term administration of the antipsychotic agent clozapine (10 and 20 mg/kg) on some age-related behavioral and organ-function tests. Compared to controls, clozapine-treated mice weighed less, had lower white-cell counts in peripheral blood, and had a shorter lifespan. Hexobarbital sleeping time of the clozapine-treated mice was elevated at 12, 16, and 20 months and decreased at 24, 28, and 32 months of age. Clozapine-treated mice had higher locomotor-activity scores (behavioral supersensitivity) at varying intervals from 12 to 24 months of age, but not at 28 and 32 months. A significant change in the total white-cell number in drug-treated mice compared to controls was also first noted at 24 months and the difference progressively increased at 28 and 32 months. These observations indicate that age may be a major factor in the level and even direction of responsiveness to longterm administration of antipsychotic agents like clozapine.