Behavioral effects of withdrawal of fluphenazine after long-term treatment

Male Wistar rats were treated i.p. with 10-(3-[4-(2-hydroxyethyl)-1-piperazinyl]-propyl)-2-(trifluoromethyl)-phenothiazine (fluphenazine dihydrochloride, FL, Mirenil) in a dose of 1 mg/kg for 28 weeks, or in a dose of 5 mg/kg for 21 weeks, beginning from the 6th day of life. Withdrawal of the drug caused an abstinence syndrome in the form of increased locomotor and exploratory activity and increased irritability of the Animals. Behavioral observation during the period of drug administration indicated the development of tolerance to behavioral effects of FL. Male and female Wistar rats from mothers treated i.p. with 1 mg/kg of FL during pregnancy and lactation period were treated for 32 weeks with 1 mg/kg of FL beginning from the 8th day of life. In males, during the period of withdrawal as well as during renewed treatment, an increase in locomotor and exploratory activity was observed. The behavior of female rats during the withdrawal period was similar to that of control Animals. The abstinence syndrome observed after withdrawal of FL is modified by the time of life at which treatment was started and by the sex of the Animals.