PDE5 inhibition improves object memory in standard housed rats but not in rats housed in an enriched environment: implications for memory models?

Drug effects are usually evaluated in animals housed under maximally standardized conditions. However, it is assumed that an enriched environment (EE) more closely resembles human conditions as compared to maximally standardized laboratory conditions. In the present study, we examined the acute cognition enhancing effects of vardenafil, a PDE5 inhibitor, which stimulates protein kinase G/CREB signaling in cells, in three different groups of male Wistar rats tested in an object recognition task (ORT). Rats were either housed solitarily (SOL) or socially (SOC) under standard conditions, or socially in an EE. Although EE animals remembered object information longer in the vehicle condition, vardenafil only improved object memory in SOL and SOC animals. While EE animals had a heavier dorsal hippocampus, we found no differences between experimental groups in total cell numbers in the dentate gyrus, CA2-3 or CA1. Neither were there any differences in markers for pre- and postsynaptic density. No changes in PDE5 mRNA- and protein expression levels were observed. Basal pCREB levels were increased in EE rats only, whereas ß-catenin was not affected, suggesting specific activation of the MAP kinase signaling pathway and not the AKT pathway. A possible explanation for the inefficacy of vardenafil could be that CREB signaling is already optimally stimulated in the hippocampus of EE rats. Since previous data has shown that acute PDE5 inhibition does not improve memory performance in humans, the use of EE animals could be considered as a more valid model for testing cognition enhancing drugs.

Long-term effects of prenatal allopurinol treatment on brain plasticity markers in low and normal birth weight piglets.

In this study, we investigated the effect of antenatal allopurinol (ALLO) treatment on levels and expression of plasticity markers in the dorsal hippocampus of low (LBW) and normal (NBW) birth weight piglets. ALLO treatment given daily in the last trimester to pregnant sows had a protective effect on neuronal plasticity markers in their piglets. ALLO increases protein levels of BDNF and the postsynaptic marker PSD95 in LBW and NBW piglets. ALLO treatment increases the pCREB/CREB ratio in LBW piglets to a similar level as that found in untreated NBW piglets. In conclusion, antioxidant treatment administered in the last trimester might be a promising treatment for LBW neonates.