Characterizing the therapeutic application of amphetamine in age‐associated cognitive decline

Abstract

Memory impairment often accompanies normal aging and is thought to involve hypofunctional glutamatergic systems in the cerebral cortex and hippocampus. Glutamate, the major excitatory neurotransmitter in the brain, plays a fundamental role in functions such as cognition, motor behavior and emotion (Meldrum, 2000). Along with glutamate, norepinephrine (NE) is an important modulator of memory, especially emotional memory (Tully et al., 2010). Our previous study demonstrated a marked deficit in glutamate-stimulated NE release in slices from the cortex and hippocampus of aged (22-24 months old) male Fischer 344 rats, which is rescued by addition of amphetamine (Dezfuli et al., 2019). Thus, amphetamine potentiates glutamate-stimulated NE release (and possibly release of other monoamines). The purpose of our current study was to test the cognitive effects of amphetamine treatment in aged rats. To do this, we investigated whether memory performance as measured in the novel object recognition task (NOR) is enhanced by acute treatment with amphetamine in aged Fischer 344 rats. An additional goal of this study, is to test the effects of chronic amphetamine treatment on the NOR task. Our initial results indicate that in aged Fischer 344 rats, acute treatment with amphetamine (0.5 mg/kg) increases object recognition memory in the NOR task. These results set the stage for our chronic studies, which will be reported.