Chronic postinjury administration of MDL 26,479 (Suritozole), a negative modulator at the GABAA receptor, and cognitive impairment in rats following traumatic brain injury

The present experiment examined the efficacy of postinjury administration of MDL 26,479 (Suritozole), a negative modulator at the gamma-aminobutyric acidA (GABAA) receptor that enhances cholinergic function, in attenuating spatial memory deficits after traumatic brain injury in the rat. Two experiments were performed. In the delayed-dosing experiment, rats received a moderate level (2.1 ATM) of fluid-percussion brain injury and were tested in the Morris water maze 11 to 15 days following injury. These rats were injected with either 5 mg/kg (eight rats) or 10 mg/kg (eight rats) of MDL 26,479 60 minutes before each water maze test. Additional rats were injured and treated with saline (eight rats) or were surgically prepared but not injured (eight rats). In the second experiment, an early postinjury dosing procedure was followed. Rats were injured in the same manner but drug treatment began 24 hours after injury and continued daily through Day 15. Results indicated that the rats in the delayed chronic dosing regimen did not differ from the injured, saline-treated rats in their latency to reach the goal platform (p > 0.05). However, those treated chronically beginning 24 hours after injury had significantly shorter latencies than the injured, saline-treated rats (p < 0.05). These results suggest that administration of agents that enhance cholinergic function may be an appropriate strategy for promoting cognitive recovery when given after traumatic brain injury. Furthermore, prolonged treatment may be necessary to elicit beneficial effects.