A COMPARATIVE-STUDY OF THE ANORECTIC AND BEHAVIORAL-EFFECTS OF FENPROPOREX ON MALE AND FEMALE RATS

The anorectic and behavioral effects of fenproporex (Fenp, 10 mg/kg, i p) and methamphetamine (Met, 2.5 mg/kg, ip), a prototypical example of an amphetamine-like drug, were studied in male and female Wistar rats (5 and 3 months of age, respectively, at the beginning of the experim ents) after acute (immediately after a single dose) or chronic treatme nt (after 60 days of administration). For the evaluation of the experi mental parameters six groups of eight rats each were utilized for food intake and stereotyped behavior and six groups of nine rats each for body weight and motor activity. Similar anorectic effects (decreased f ood intake in grams: saline (Sal): 12.8 +/- 2.5, Met: 4.7 +/- 4.0, and Fenp: 4.4 +/- 20; decreased weight gain: Sal: 38 +/- 10, Met: 25 +/- 1.0, and Fenp: 27 +/- 3.0) were induced by both drugs in male rats. Fe male rats, however, required larger doses (20 mg/kg Fenp and 5.0 mg/kg Met) for a complete blockade of food intake. The behavioral tests wer e carried out 30, 60, 120, 180 and 300 min after drug administration a nd on day 1 and day 60 immediately after the treatment, for stereotypy and motor activity, respectively (male rats: Met: 3.8 +/- 0.3, Fenp: 6.0 +/- 0.9, and female rats: Met: 15.4 +/- 1.9, Fenp: 9.7 +/- 1.3). T hough stereotyped behavior such as sniffing, continuous licking, and f alse bites was observed in all animals, this was more evident and prol onged in female rats. Both drugs also increased motor activity (male r ats, acute treatment: Met: 608 +/- 419, Fenp: 677 +/- 354; chronic tre atment: Met: 701 +/- 423, Fenp: 908 +/- 479; female rats, acute treatm ent: Met: 817 +/- 350, Fenp: 1177 +/- 282; chronic treatment: Met: 623 +/- 274, Fenp: 1511 +/- 573) with female rats once again showing grea ter sensitivity both after acute and chronic treatment. Our data indic ate that fenproporex, like methamphetamine, has a stimulating effect o n the central nervous system, indicating an action on the dopaminergic systems. These data further suggest that its therapeutic use as an ap petite moderator should be prescribed with caution, especially to wome n, since, at least in the species studied, the female organism seems t o show higher susceptibility to the central effects of this substance.