Excitatory amino acids and memory: evidence from research on Alzheimer's disease and behavioral pharmacology.
The excitatory amino acid transmitter (EAA) system is believed to play a crucial role in a variety of physiological processes related to neuronal plasticity. Substantial neurophysiological evidence suggests that, under normal physiological conditions. EAAs may be involved in mechanisms underlying learning and memory. However, overactivity of this system produces excitotoxic damage to neurons which is believed to be an etiological factor in various neurological conditions, such as epilepsy, and stroke-induced impairments. The fact that EAAs have been implicated in both, normal cognitive function and in degenerative neurological conditions suggests that they may contribute to the etiology of Alzheimer's disease (AD), because AD is characterized by memory deficits and specific histopathological signs of neuronal damage. This paper summarizes information regarding 1) the involvement of EAAs in Alzheimer's disease and 2) results from psychopharmacological studies of EAAs in laboratory animal models of learning. Investigations of the pathophysiology of AD indicate that glutamatergic deficits are associated with this syndrome. However, there is controversy concerning the nature of this defect. As a result, it is unclear whether it is a consequence of excitotoxic changes produced by glutamatergic overactivity or result from a decrease in glutamatergic function. Evidence from behavioral studies is consistent with the conclusion that EAAs may be involved in the acquisition of conditioned responses. However, in parallel with the clinical findings, learning impairments have been produced by treatments which either increase or decrease activity within this transmitter system. Therefore, although present results suggest that the EAAs play a role in cognition and in clinical syndromes in which such function is compromised, the specific nature of that role needs to be elucidated by future research.
Advokat
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Department of Psychology, Louisiana State University, Baton Rouge 70803.
Pellegrin
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D000544:Alzheimer Disease / Q000503:physiopathology / Q000523:psychology*; D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D001519:Behavior / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D006801:Humans; D008568:Memory / Q000502:physiology*
D000596:Amino Acids