Age-related deficits in the retention of memories for cued fear conditioning are reversed by galantamine treatment

Aging has diverse effects on different behaviors and underlying neural systems. This study utilized fear conditioning to determine if aged mice have deficits in the acquisition and/or retention of memories for contextual or cued fear conditioning, and to determine if galantamine, an acetylcholinesterase (AChE) inhibitor and allosteric modulator of nicotinic acetylcholinergic receptors, would alter acquisition and/or retention of fear conditioning memories in young (2-3 months) and aged (19-20 months) C57BL/6 mice. Mice were trained with two white-noise CS (85 dB, 30 s)-footshock US (0.57 mA, 2 s) presentations. In the initial study, separate groups were tested 24, 48, or 96 h post-training. All mice were retested 1 week after the initial test. Aged mice were impaired in freezing to the CS for the 48 and 96 h train-test intervals, but not the 24-h interval. When retested 1 week after the initial test, freezing to the CS was significantly lower for all train-test intervals. No age-related deficits were found in contextual fear conditioning. In the second study, 2 mg/kg galantamine was administered to young and aged mice before fear conditioning and conditioned fear was assessed 48 h later. No age-related deficits in cued fear conditioning were seen in galantamine-treated aged mice. Thus, aged C57BL/6 mice are impaired in the long-term retention of auditory cued fear conditioning, but not the acquisition of auditory cued or contextual fear conditioning. This retention deficit for cued fear conditioning is ameliorated by treatment with the AChE inhibitor galantamine.