Search for a command to run...
P77 D-amphetamine can facilitate recovery after cortical injury, however, little is known of its neuroregenerative properties following proximal middle cerebral aretery occlusion (MCAO). The aim of this experiment was to investigate the recovery promoting effects of d-amphetamine following transient MCAO in the rat. Rats were pre-trained on the beam-walking test and then underwent 90 min of MCAO using an intraluminal filament and randomly assigned to receive either d-amphetamine (Amp, 2 mg/kg i.p) or vehicle (Veh, 0.9 % saline, i.p.) at 1, 3 and 5 days post-surgery. Performance on the beam-walking test was assessed at 1, 7, 14, 21 and 28 days post-surgery. A graded 21-point neurological score (21 = normal)and body weight were also assessed. There was a significant Group x Time Interaction [F (5,70) = 2.61, p = 0.032] for the effects of Amp on total distance travelled by MCAO rats. Post-hoc t -tests revealed both groups of rats were matched for impairments on the beam at 1 day prior to drug administration (Mean ± SEM (in cm): Amp = 8.90 ± 6.56; Veh = 21.56 ± 11.85, p s<0.001 relative to pre-op baseline, 100 ± 0), but the effect of Amp significantly impaired the recovery process throughout the post-operative testing period (7 days = 20.19 ± 11.75; 14 days = 36.94 ± 14.31; 21 days = 47.00 ± 15.72; and 28 days = 51.25 ± 15.04, p s < 0.05). The significant impairment displayed by Amp-treated animals was in direct contrast to Veh-treated animals which improved dramatically in performance from 7–28 days (7 days = 63.88 ± 16.73; 14 days = 86.25 ± 11.16; 21 days = 88.31 ± 11.68; and 28 days = 89.38 ± 10.62). The deficits attributed to Amp animals were also reflected in impaired neurological performance at 21 days (Median + IQR (total score): Amp = 14 ± 1.5; Veh = 16.5 ± 2.5; p<0.05) and 28 days (Amp = 15 ± 2; Veh = 17 ± 3; p<0.05). Total body weight for Amp-treated animals was significantly reduced relative to Veh-treated animals throughout post-operative testing, from 7 to 28 days (Mean ± SEM (in g): e.g 7 days, Amp = 316 ± 14, Veh = 361 ± 6; and 28 days, Amp = 377 ± 17, Veh = 449 ± 9, p s < 0.05). Results indicate amphetamine impairs neurological recovery in a model where extensive sub-cortical damage exists.