Enkephalin content in rat striatum during prolonged treatment with fluphenazine

Male Wistar rats were injected with fluphenazine /FLU/ i.p. in doses of 1 or 5 mg/kg for twelve months. Striatal met- and leu-enkephalin contents were determined after 1, 3, 6, 9 and 12 months of treatment, and one week after the drug withdrawal following a 12-month treatment, Enkephalin levels were significantly increased with slight fluctuations in some months and returned to normal one week after the last neuroleptic dose following a 12-month administration. Apomorphine, but not naloxone, prevented elevation of enkephalin levels after a one month FLU administration. Our findings confirm previous observations that prolonged disturbances in functions of the dopaminergic mechanism result in specific disturbances in the endogenous opioid peptide content, release and biosynthesis, and demonstrate that enkephalins are one of the factors with take part in the mechanism of neuroleptic action during a long-term treatment.