Acute ethanol administration affects memory reactivation: a look at the neuronal density and apoptosis in the rat hippocampus.

This study is an attempt to examine whether administration of ethanol after memory reactivation will modulate expression of memory in rats or not. We further examined whether this administration alters the number of tunnel positive cells in hippocampus. Adult male Wistar rats were trained in a fear conditioning system using two 1s , 0.6 mA shock with an interval of 180 s. 24 h later the rats were returned to the chamber for reactivation, and then they were injected with ethanol (0.5, 1, 1.5 mg/kg) or saline, ip. Again, one, seven and fourteen days after reactivation, the rats were returned to the context for 5 min. The freezing time (absence of all movements except respiration) was scored in seconds. In the second experiment, after test 1, the animals were anesthetized and a transcardial perfuse with phosphate buffer and paraformaldehyde 4% was conducted. After post-fixation of brains 5-µm sections were stained with cresyl violet. Finally, paraffin-embedded sections of 10 µm were cut out throughout the tissue and each sample was processed with TUNEL. The number of apoptotic cells in a 130 µm-long segment of the hippocampal CA1 and CA3 fields and dentate gyrus was counted. The data demonstrate that ethanol exposure impairs post retrieval processes. Rats receiving ethanol (1.5 mg/kg) showed lower freezing levels during the first test. Moreover, ethanol decreases the density of CA1, CA3 and DG cells and increases the density of apoptotic cells in all regions of hippocampus. Therefore, ethanol exposure impairs reconsolidation of contextual fear conditioning probably via decreasing the density of CA1, CA3 and DG cells.

Administration of corticosterone after memory reactivation disrupts subsequent retrieval of a contextual conditioned fear memory: dependence upon training intensity.

Reactivation of stabilized memories returns them to a labile state and causes them to undergo extinction or reconsolidation processes. Although it is well established that administration of glucocorticoids after training enhance consolidation of contextual fear memories, but their effects on post-retrieval processes are not known. In this study, we first asked whether administration of corticosterone after memory reactivation would modulate subsequent expression of memory in rats. Additionally, we examined whether this modulatory action would depend upon the strength of the memory. We also tested the effect of propranolol after memory reactivation. Adult male Wistar rats were trained in a fear conditioning system using moderate (0.4 mA) or high shock (1.5 mA) intensities. For reactivation, rats were returned to the chamber for 90 s 24h later. Immediately after reactivation, rats were injected with corticosterone (1, 3 or 10mg/kg) or vehicle. One, 7 and 14 days after memory reactivation, rats were returned to the context for 5 min, and freezing behavior was scored. The findings indicated that corticosterone when injected after memory reactivation had no significant effect on recall of a moderate memory, but it impaired recall of a strong memory at a dose of 3mg/kg. Propranolol (5mg/kg) given after the reactivation treatment produced a modest impairment that persisted over three test sessions. Further, the results showed that corticosterone, but not propranolol deficit was reversed by a reminder shock. These findings provide evidence that administration of glucocorticoids following memory reactivation reduces subsequent retrieval of strong, but not moderate, contextual conditioned fear memory likely via acceleration of memory extinction. On the other hand, propranolol-induced amnesia may result from blockade of reconsolidation process. Further studies are needed to determine the underlying mechanisms.