1. No specific regimen has been developed to treat post-traumatic
amnesia in man. In the present study, we examined the effects of (+)-eburnamenine-14-
carboxylic acid (2-nitroxyethyl)
ester (VA-045), a novel derivative of
apovincaminic acid, on learning and
memory deficits associated with a
mild traumatic brain injury (TBI) in mice. 2. Two kinds of
amnesia, TBI-induced
retrograde amnesia (TRA) and
anterograde amnesia (TAA), were produced by means of post- and pre-acquisition
head injury, respectively, by a simple weight-drop device. A novel procedure of water-finding task was used to assess learning and memory functions. 3. Both TRA and TAA mice were dramatically impaired in the task performance, with prolonged latencies for finding and drinking in either retention test or retest, indicating that retention was impaired in TRA mice while learning and retention were impaired in TAA mice. 4.
VA-045 administered 30 min post-
trauma in TRA mice dramatically shortened the prolonged latencies for finding and drinking in both retention test and retest, indicating that
VA-045 significantly improved the retention deficit observed in TRA mice. 5.
VA-045 administered 30 min post-
trauma in TAA mice dramatically attenuated the prolonged latencies for finding and drinking in both retention test and retest, indicating that
VA-045 significantly improved the learning and retention deficits observed in TAA mice. 6. Administration of
VA-045 30 min pre-
trauma in normal mice markedly attenuated the delay of latencies for finding and drinking after
trauma in both retention test and retest, which shows that
VA-045 significantly prevented learning and retention deficits after TBI. 7. Motor activities were not significantly affected by either the TBI or the chemical treatment at the time of task examination in either experimental model. 8. It is concluded that
VA-045 may have potential effects on learning and
memory deficits observed in either TBI-induced retrograde or
anterograde amnesia.