Age-related effects of diazepam on retention of inhibitory avoidance and shuttle avoidance tasks in rats

We investigated the effect of diazepam on memory of 30 days-old and 60-70 days-old female Wistar rats, using two behavioral tasks: step-down inhibitory avoidance (IA) and shuttle avoidance (SA). Diazepam (0.2,1.0 or 5.0 mg/kg) or its vehicle were given i.p., 60 min prior to the training session. Training-test interval was 24h. Diazepam impaired the retention of IA in 30 days-old rats at the three doses used, while retention of SA was not impaired by any dose. In the 60-70 days-old animals, diazepam at the dose of 0.2 mg/kg was facilitatory in IA and had no effect on SA, while doses of 1.0 mg/kg and 5.0 mg/kg impaired retention of both tasks. We suggest that these age-dependent effects of diazepam on memory of IA and SA could be related to developmental changes in brain GABA(A) receptors.

Experiments suggesting a role for the platelet-activating factor in hippocampal and amygdala synapses in memory in rats

Platelet-activating factor (1-O-alky1-2-acetyl-sn-glycero-3-phosphocholine, PAF) is present in brain, is released from neurons in culture and, in hippocampal slices, enhances glutamate release and long-term potentiation (LTP) through an action on membrane receptors sensitive to the antagonist, BN 52021. This led to the proposal that PAF may be a retrograde messenger in the genesis of LTP. LTP has been, in turn, proposed as a mechanism of memory. Male Wistar rats were implanted bilaterally with cannulae aimed at the amygdala and the dorsal hippocampus. After recovery from surgery, the animals were trained in step-down inhibitory avoidance using a 0.5 mA footshock, and tested for retention 24 h later. BN 52021 (0.5 mug) was amnestic when given into the hippocampus or the amygdala either before or immediately after training but not 30 min later. The findings support the idea that memory of this task depends on the generation of LTP at the time of training in hippocampus and amygdala, and further suggest that PAF is involved in the development of this LTP.