Behavior of rats during one-year administration of fluphenazine and subsequent withdrawal period

During one-year administration of fluphenazine [FLU], 1 or 5 mg/kg/d ip. two phases in the behavior of rats were observed. During the first four months of treatment the locomotor and exploratory activities were depressed, while during the following months the reversal of this phenomenon was observed, and the activity of FLU-treated rats increased, particularly in the open-field test. The irritability of rats showed a triphasic change during one year treatment with 5 mg/kg/d FLU. Catalepsy declined with the increase in length of treatment and dose of FLU during the first three months of experiment. During the first 2 weeks of FLU withdrawal the locomotor and exploratory activities and irritability of rats increased. The behavioral differences between controls and FLU-pretreated rats were observed between the 6th and 8th day of withdrawal period. The results demonstrated the occurrence of multiphasic changes in the behavior of rats during one year administration of FLU and after its withdrawal. They warrant further studies on the central nervous system reactivity during a prolonged neuroleptic therapy and after its cessation in man.