NMDA Receptor‐ Mediated Release of Norepinephrine and Dopamine in Rat Brain: Effects of Ageing

Abstract

A greater understanding of the neural changes occurring in the aging brain can facilitate the identification of possible molecular target(s) for pharmacological intervention to offset age-related cognitive deficits. Selective age-related vulnerabilities of glutamate neurotransmission have been found, as well as studies indicating age-related changes in the interaction between glutamate and other neurotransmitters (e.g. norepinephrine, dopamine). Previously, we have demonstrated that in brains from aged Fischer 344 rats, a model of neurocognitive aging, there is a marked deficit in glutamate-stimulated norepinephrine (NE) release measured in vitro in the hippocampus and cerebral cortex, and that this deficit is rescued by the addition of d-amphetamine sulfate (Dezfuli et al., 2019). Thus, amphetamine potentiates glutamate-stimulated NE release (and possibly release of other neurotransmitters). The purpose of the present study was to expand on our previous findings by (a) determining if glutamate-stimulated NE release is mediated by NMDA receptors and (b) investigating if there is a comparable deficit in glutamate-stimulated dopamine (DA) release in the aged Fischer 344 rat brain and whether it can also be rescued by amphetamine. To this end, experiments were performed in both young (2-3 months old) and aged Fischer 344 rats (18-22-month-old). The cerebral cortex was used for measuring glutamate-stimulated NE release, and the olfactory tubercle and striatum were used for measuring glutamate-stimulated DA release. Our results show that glutamate-stimulated NE release in the rat cortex is mediated exclusively by NMDA receptors. Results from the dopamine studies are ongoing and will be reported.