The behavioral sensitization induced by fencamfamine is not related to plasma drug levels

Fencamfamine (FCF) is a CNS stimulant that facilitates central dopaminergic transmission primarily though blockade of dopamine uptake. In the present study we evaluated the relationship between plasma FCF concentration and behavioral sensitization effect. Adult male Wistar rats (250-300 g) received FCF (10 mg/Kg, ip) or saline oince or daily for 10 consecutive days (N = 10 for each group). Blood samples were collected 30 min after injections and plasma FCF was measured by gas chromatography using an electron capture detector. FCF treatment enhanced sniffing duration (16.8 ñ 0.8 vs 26.6 ñ 0.9s) and decreased rearing behavior (8.2 ñ 0.8 vs 3.7 ñ 0.6s) when days 1 and 10 of drug administration were compared. Comparison of pair of means by the Student t-test did not show significant differences in plasma FCF concentration (390 ñ 40 vs 420 ñ 11 ng/ml) when blood samples were collected 30 min after acute FCF administration or after daily administration of 10 mg/Kg for 10 days. In conclusion, the behavioral sensitization to FCF could not be correlated with plasma drug levels, and changes in the activity of dopaminergic systems should be considered to explain the sensitization to the effect of FCF

Daily variation in plasma concentration of fencamfamine and striatal dopamine receptors in rats

Fencamfamine (FCF) is a psychostimulant drug classified as an indirect dopamine agonist. In the present study we evaluated the daily variation in plasma FCF concentration and in striatal dopamine receptors. Adult male Wistar rats (250-300 g) maintained on a 12-h light/12-h dark cycle (lights on at 07:00 h) were used. Rats received FCF (10.0 mg/kg, ip) at 09:00, 15:00, 21:00 or 03:00 h and blood samples were collected 30 (N = 6) or 60 (N = 6) min after the injections. Plasma FCF was measured by gas chromatography using an electron capture detector. Two-way ANOVA showed significant differences in FCF concentration when blood samples were collected 30 min after the injection, and the highest value was obtained following injection at 21:00 h. Moreover, at 15:00, 21:00 and 03:00 h, plasma FCF levels were significantly lower 60 min after injection when compared to the 30-min interval. Two other groups of rats (N = 6) were decapitated at 09:00 or 21:00 h and the striata were dissected for the binding assays. The Bmax for [3H]-spiroperidol binding to striatal membranes was higher at 21:00 h, without changes in affinity constant (Kd). In conclusion, plasma FCF levels and dopamine receptors undergo daily variation, a phenomenon that should be considered to explain the circadian time-dependent effects of FCF