Norepinephrine mediates effects of chronic amphetamine on memory performance in aged rats

Abstract

Understanding the neural mechanisms of normal and pathological aging is increasingly important as the average lifespan continues to rise. Memory impairment is attributed to normal aging processes, with the hippocampus and the cerebral cortex playing key roles in the encoding and retrieval of memories. Norepinephrine (NE) is an important modulator of memory, especially emotional memory (Tully et al., 2010). Previously, we demonstrated that acute treatment with amphetamine (0.5mg/kg) enhances memory performance on the novel object recognition (NOR) task in aged Fischer 344 rats, with a reversible and short‐term effect (Scognamiglio et al., 2021). The purpose of this study was to investigate whether chronic amphetamine treatment has a more robust and possible long‐term effect on memory performance in aged rats and whether the effect of amphetamine on object recognition memory is NE‐ dependent. To this end, in the first set of experiments we administered amphetamine for 2 weeks via drinking water at doses of 0.25 mg/kg (week 1) and 0.5 mg/kg (week 2) and tested aged Fischer 344 rats on the NOR task. To determine the extent to which NE influences the cognitive effects of amphetamine, we examined the effects of systemic administration of the β‐ and α‐adrenergic antagonists propranolol, metoprolol, and prazosin prior to the NOR test phase in aged rats chronically treated with amphetamine. The present studies found: (a) aged rats chronically treated with amphetamine displayed improved object recognition memory compared to rats treated acutely, (b) memory performance returned to baseline 2 months after chronic amphetamine treatment, (c)all three of the β‐ and α‐ adrenergic antagonists abolished the effect of amphetamine on memory performance in the NOR test. An additional goal of this study was to assess the outcome of chronic amphetamine treatment on a cellular level by analyzing dendritic spines in the cerebral cortex and hippocampus. The results of those studies will be reported.