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 variati on in plasma FCF concentration and in striatal dopamine receptors. Adu lt male Wistar rats (250-300 g) maintained on a 12-h light/12-h dark c ycle (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 mea sured by gas chromatography using an electron capture detector. Two-wa y ANOVA showed significant differences in FCF concentration when blood samples were collected 30 min after the injection, and the highest va lue was obtained following injection 21:00 h. Moreover, at 15:00, 21:0 0 and 03:00h, plasma FCF levels were significantly lower 60 min after injection when compared to the 30-min interval. Two other groups of ra ts (N = 6) were decapitated at 09:00 or 21:00 h and the striata were d issected for the binding assays. The Bmax for [H-3]-spiroperidol bindi ng to striatal membranes was higher at 21:00 h, without changes in aff inity constant (Kd). In conclusion, plasma FCF levels and dopamine rec eptors undergo daily variation,a phenomenon that should be considered to explain the circadian time-dependent effects of FCF.