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NMDA Receptor‐ Mediated Release of Norepinephrine and Dopamine in Rat Brain: Effects of Ageing
Author(s) -
Aljohani Yousef,
Dezfuli Ghazaul,
Vernik Daniel,
Kellar Kenneth
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05270
Subject(s) - glutamate receptor , dopamine , nmda receptor , amphetamine , neurotransmitter , neuroscience , medicine , chemistry , norepinephrine , endocrinology , biology , receptor
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.