Neuroleptic-like effects of the ι-isomer of fenfluramine on striatal dopamine release in freely moving rats

Abstract ι-Fenfluramine (ι-F) was studied for its ability to release dopamine (DA) and its metabolites in freely moving rats through the trans-striatal dialysis technique. ι-F's effect on striatal DA release was also studied in animals made tolerant to the effect of haloperidol by chronic treatment (1 mg/kg i.p. twice daily for 11 days and 48 hr wash-out) with the neuroleptic or pretreated with 300 mg/kg i.p. gamma-butyrolactone (GBL). Five and 10 mg/kg ι-F dose-dependently increased the release of DA and its metabolites with a pattern of effects similar to that observed with neuroleptic drugs. The dose of 20 mg/kg ι-F had the same effect as 10 mg/kg. Repeated haloperidol treatment reduced the basal release of DA and its metabolites and a much smaller amount of DA and metabolites was released by ι-F (10 mg/kg i.p.) and haloperidol (0.1 mg/kg i.p.) in animals treated with haloperidol than in controls. GBL 300 mg/kg i.p. reduced basal DA release by about 50%. When 10 mg/kg ι-F, 0.1 mg/kg haloperidol and 0.25 mg/kg d -amphetamine were injected i.p. 40 min after GBL, ι-F and haloperidol did not significantly raise DA release in GBL-treated rats whereas a significant effect was observed at various times after d -amphetamine. The data show that ι-F resembles haloperidol in its ability to release DA and its metabolites from the corpus striatum of freely moving rats. The cross-tolerance between haloperidol and ι-F for their effect on DA release suggests that a common site is involved in the mechanism of these drugs.