EFFECT OF D-FENFLURAMINE ON CORTICAL SPREADING DEPRESSION IN RATS

We investigated the effect of a single ip injection of d-fenfluramine (d-fen; 5-10 mg/kg), a serotonin reuptake blocker, on cortical spreadi ng depression (SD) in 17 male Wistar rats (300-360 g body weight). SD was elicited at the right frontal cortex by 1-min application of 2% KC l at 20-min intervals. SD propagation was monitored (electrocorticogra m and DC-recording) at 2 points on the right parietal surface for 3 h. After a ''baseline'' recording period (1 h), d-fen was injected and t he recording session was continued for 2 h. When compared to the predr ug SD velocities (t = 0 min) the values measured after d-fen decreased significantly at t = 20 min (3.44 +/- 0.63 vs 2.66 +/- 0.51 mm/min; N = 17, P<0.001), at t = 40 min (3.32 +/- 0.58 vs 2.53 +/- 0.52 mm/min; N = 14, P<0.001), at t = 60 min (3.68 +/- 0.63 vs 2.92 +/- 0.72 mm/mi n; N = 11, P<0.001) and at t = 80 min (3.57 +/- 0.61 vs 3.03 +/- 0.83 mm/min; N = 12, P<0.05) but not at t = 100 min (3.47 +/- 0.72 vs 3.31 +/- 0.88 mm/min; N = 12) nor at t = 120 min (3.44 +/- 0.67 vs 3.37 +/- 0.76 mm/min; N = 11). Furthermore, in 19 of 48 KCl stimulations (40%) performed after d-fen in 8 rats (47%), SD velocity could not be evalu ated since the phenomenon, after reaching the recording electrode near est the stimulating point, interrupted the propagation before the seco nd recording electrode was reached. The reduction of the propagation o f cortical SD and its blockade by d-fen probably are related to an inc rease in the availability of extracellular brain serotonin.