PharmacologyBtochemtstry&Behavtor, Vol 10, pp 505--512 Prmtedm the U S A Behavioral Effects of Aluminum Ingestion On Animal and Human S u b j e c t s 1"2 NOELLE C. BOWDLER 3, DEBBIE S. BEASLEY, E. CRISTINA FRITZE, ANN M. GOULETTE, JAMES D. HATTON, JAMES HESSION, DAVID L. OSTMAN, DAVID J. RUGG AND CHARLES J. SCHMITTDIEL Michigan State Universtty, Departments of Psychology and Zoology East Lansing, MI 48824 (Received 2 June 1978) BOWDLER, N C, D S BEASLEY, E C FRITZE, A M GOULETTE, J D HATTON, J HESSION, D L OSTMAN, D J RUGG AND C J SCHMITTDIEL Behavtora/effects of aluminum mgestton on aroma/and human subjects PHARMAC BIOCHEM BEHAV 10(4)505-512, 1979--Abnormallyhlghbrmnalummumconcentratlonshave been detected m hemodialysls patients who &ed of an unexplained encephalopathy As a result, this study was undertaken to examine whether the mgestaon of aluminum produces behavioral aberrations m non-dtalysed human subjects and rats with ostensibly normal renal function Rats were fed A1CI~ by mtubatlon m varying doses, and tests measunng learning abdlty, v~sual temporal acmty, motor coordination and actlwty were administered It was found that orally ingested alurmnum Is absorbed by rats and deposited m the brmn High brmn alurmnum levels are assocmted with rapid general acUwty, decreased abd~ty to mamtmn roto-rod activity, and increased sensmv~ty to fl~cker Behavioral tests were also given to elderly human subjects and performance correlated with serum aluminum level High serum levels of aluminum in elderly humans are assocmted with impaired VlSUO-motor coordination, poor long-term memory, and increased sensmv~ty to flicker Alurmnum Behavior Toxlc~ty Antacids PRIOR research has suggested that aluminum ingestion may be causally related to various neurological and behavioral abnormalmes. Several studies of hemo&alysls patients re- ceiving alummum-containlng phosphate-bmdmg gels have reported patients to develop a progressive form of dementm which results m death [1, 8, 12]. The dementm is char- acterized by such clinical symptoms as paranom, confusion, impaired ability to perform numerical tasks, and delirium [12]. In one invesUgatlon of patient deaths preceded by encephalopathy, unusually high levels of aluminum were de- tected in the patients' muscle, bone and brain tissue [1] An analysis of cerebral grey matter revealed an aluminum level of 25 parts per rmllion (ppm) in the dialysis patients with the encephalopathy, as opposed to 6.5 ppm m &alysls patients who had died of other disorders. A control group of non- dialyzed subjects was found to have a level of 2.2 ppm. From these results, the authors concluded that the encephalopathy may have been related to aluminum intoxication. Studies employing animal subjects found that oral and parenteral administration of aluminum salts resulted In alu- minum intoxicataon characterized by penorbital bleeding, lethargy, anorexia and death. For both nephrectom~zed and non-nephrectomized rats given daffy alummum salt treat- ments, elevated aluminum levels were reported m plasma, hver, heart, striated muscle, brain and bone [2]. Another study [14], had shown orally ingested aluminum to be depos- ited m measurable amounts in the t~ssues of rats, especmlly when administered as aluminum hydroxide, a major compo- nent of several commercially avadable antacids for human use. Aluminum ingestion has also been shown to be associated with neurological and behavioral disorders in normal animal subjects. A team of investigators [6,7] found aluminum to reduce neurofibrillary degeneration (NFD) when rejected into the h~ppocampus, entorhmal cortex, and neocortex of cats. Another study [10] reported an absence m the cat visual cortex of neurons with spontaneous finng frequencies be- tween 7 and 12 spikes per second 10 days after hippocampal injections of A1CI 3 This finding was attributed as an effect of NFD caused by elevated aluminum concentrations m the lateral gyrus The clinical features observed m the cats of these studies were slmdar to those seen m patients with Alzhelmer's &s- ease, which ~s characterized by dementia It was noted that some brain regions m the victims of Alzhe~mer's &sease contmned rinsed aluminum concentrations, particularly the regions of the cerebral cortex likely to exhibit NFD [1,9]. That paUents with Alzhelmer's &sease also showed an 1This research was supported by Grant No 77-05159from the National Science Foundation 2Repnnts may be requested m care of Dr James Zacks, Department of Psychology, Michigan State University, East Lansing, M148824 aproJect D~rector Copyright © 1979 ANKHO International Inc.--0091-3057/79/040505-08501.30/0