CHRONIC TREATMENT WITH ELTOPRAZINE DOES NOT LEAD TO TOLERANCE IN ITS ANTIAGGRESSIVE ACTION, IN CONTRAST TO HALOPERIDOL

The behavioral effects of eltoprazine and haloperidol during a 4 week treatment period were studied in the resident-intruder model of aggres sion in male rats. Eltoprazine, a serotonergic (5-HT1A/1B) agonist wit h specific anti-aggressive actions in animals, was compared to haloper idol, a neuroleptic often used to control behavioral disorders. Eltopr azine(1 or 3 mg/kg p.o.) and haloperidol (2 mg/kg p.o.) were given 60 min before a 10 min aggression test. Acutely, eltoprazine reduced aggr ession, without adversely affecting other behaviors. Eltoprazine (1 or 3 mg/kg p.o.) was subsequently given daily for 4 weeks and aggression tests were performed each week. The anti-aggressive effects of eltopr azine remained stable over the period of 4 weeks whereas exploration w as increased. After a wash-out period of 1 week aggression had returne d to baseline levels. Acutely given, haloperidol (2 mg/kg p.o.) comple tely reduced aggression concomitant with massive sedation. Significant tolerance developed to the sedatory actions of haloperidol over the 4 week treatment period. Aggression returned slowly, but remained below baseline values. One week after wash-out a new challenge with haloper idol (2 mg/kg p.o.) revealed significant tolerance. After 2 weeks wash -out aggression had returned to baseline. The data demonstrate persist ent and specific anti-aggressive effects after eltoprazine showing no tolerance. In contrast, haloperidol showed tolerance and rebound effec ts for aggression. The development of tolerance after haloperidol has a different course for sedation than for the anti-aggressive action.