Glutamate-mediated excitotoxicity has been shown to contribute to cellular 
dysfunction following traumatic brain injury (TBI). Increasing inhibitory 
function through stimulation of gamma-aminobutyric acid (GABA(A)) receptors may 
attenuate excitotoxic effects and improve outcome. The present experiment 
examined the effects of diazepam, a positive modulator at the GABA(A) receptor, 
on survival and cognitive performance in traumatically brain-injured animals. In 
experiment 1, 15 min prior to central fluid percussion brain injury, rats (n=8 
per group) were injected (i.p.) with saline or diazepam (5 mg/kg or 10 mg/kg). 
Additional rats (n=8) were surgically prepared but not injured (sham-injury). 
Rats pre-treated with the 5 mg/kg dose of diazepam had significantly lower 
mortality (0%) than injured, saline-treated rats (53%). Also, diazepam-treated 
(5 mg/kg) rats had significantly shorter latencies to reach the goal platform in 
the Morris water maze test performed 11-15 days post-injury. In experiment 2, at 
15 min post-injury, rats were given either saline (n=5) or 5 mg/kg diazepam 
(n=6). Rats treated with diazepam did not differ in mortality from injured rats 
treated with vehicle. However, rats treated with diazepam at 15 min post-injury 
had significantly shorter latencies to reach the goal platform in the Morris 
water maze than injured, vehicle-treated rats. In experiment 3, the post-injury 
administration of bicuculline (1.5 mg/kg, n=8), a GABA(A) antagonist, increased 
Morris water maze goal latencies compared to injured animals treated with saline 
(n=8). These results suggest that enhancing inhibitory function during the acute 
post-injury period produces beneficial effects on both survival and outcome 
following experimental TBI.