A comparative study of the anorectic and behavioral effects of fenproporex on male and female rats

RESUMO

The anorectic and behavioral effects of fenproporex (Fenp, 10 mg/kg, ip) 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 experiments) after acute (immediately after a single dose) or chronic treatment (after 60 days of administration). For the evaluation of the experimental 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 food intake in grams saline(Sal) 12.8 ñ 2.5, Met 4.7 ñ 4.0, and Fenp 4.4 ñ 20; decreased weight gain Sal 38 ñ 10, Met 25 ñ 1.0, and Fenp 27 ñ 3.0) were induced by both drugs in male rats. Female 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 were carried out 30, 60, 120, 180 and 300 min after drug administration and on day 1 and day 60 immediately after the treatment, for stereotypy and motor activity, respectively (male rats Met 3.8 ñ 0.3, Fenp 6.0 ñ 0.9, and female rats Met 15.4 ñ 1.9, Fenp 9.7 ñ 1.3). Though stereotyped behavior such as sniffing, continuous licking, and false bites was observed in all animals, this was more evident and prolonged in female rats. Both drugs also increased motor activity (male rats, acute treatment Met 608 ñ 419, Fenp 677 ñ 354; chronic treatment Met 701 ñ 423, Fenp 908 ñ 479; female rats, acute treatment Met 817 ñ 350, Fenp 1177 ñ 282; chronic treatment Met 623 ñ 274, Fenp 1511 ñ 573) with female rats once again showing greater sensitivity both after acute and chronic treatment. Our data indicate that fenproporex, like methamphetamine, has a stimulating effect on the central nervous system, indicating an action on the dopaminergic systems. These data further suggest that its therapeutic use as an appetite moderator should be prescribed with caution, especially to women, since, at least in the species studied, the female organism seems to show higher susceptibility to the central effects of this substance.