Amphetamine modulation of long term object recognition memory in rats: Influence of stress

Amphetamine is a potent psychostimulant which increases the release of norepinephrine, a neurotransmitter crucially involved in the regulation of memory for stressful experiences. Here we investigated amphetamine effects on consolidation of long term object recognition memory in rats exposed to different stressful conditions. In a second set of experiments, we evaluated whether such effects were dependent on the activation of the peripheral adrenergic system. Immediately after training, adult male Sprague Dawley rats were injected with amphetamine (0.5 – 1 mg/Kg), and submitted to 1 min (25 ± 1 °C) or to 5 min (19 ± 1 °C) forced swim stress (mild and strong stressful conditions, respectively). Retention tests were performed 24 h later. Amphetamine enhanced memory consolidation in rats subjected to the mild stress condition while impairing it in rats subjected to strong stress after training. These dichotomic effects seem to depend on the stress induced activation of the peripheral adrenergic response. In rats unable to synthetize epinephrine (subjected to surgical removal of adrenal medulla) we found opposite effects. In the mild stress condition amphetamine not only lost the capability to enhance memory consolidation but it impaired memory performances, whereas in rats subjected to strong stress after training it ameliorated memory discrimination. Our results are in line with the inverted U-shaped relationship existing between stress levels and memory performances, underlining that the peripheral adrenergic response is a key player in the modulation of amphetamine modulation of long term memory.