Behavioral assessment of the toxicity of aspartame

Mark D. Holder*, Raz Yirmiya

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Six experiments with rats assessed the toxicity of aspartame with behavioral measures. The first three experiments used a conditioned taste aversion procedure since taste aversions are typically observed after a taste is followed by a toxin. Thirty min after thirsty rats drank a sweet solution they were intraperitoneally injected (Experiment 1) or intragastrically intubated (Experiment 2) with saline or 176, 352, or 704 mg/kg of aspartame. Relative to rats given saline, rats injected with 704 and 352 mg/kg aspartame showed strong and mild aversions, respectively. Rats injected with 176 mg/kg of aspartame or intubated with any dose of aspartame did not show taste aversions. In Experiment 3, rats voluntarily consumed an aspartame solution sweetened with saccharin for 7 hr each day. Consumption of the taste paired with aspartame was not reduced. When 352 mg/kg aspartame was injected (Experiment 4), but not when intubated (Experiment 5), 5 min prior to access to a running wheel, running was reduced. Wheel running was not affected by the voluntary consumption of aspartame (Experiment 6). The route of administration effect (intraperitoneal vs. intragastric) on behavior corresponded with the amino acid levels in blood plasma (Experiment 7). Aspartate, phenylalanine, tyrosine and glutamate levels increased more after the injection, than the intubation, of aspartame (176 mg/kg). Overall, the results suggest that aspartame may have adverse effects when intraperitoneally injected but not when the route of administration is oral.

Original languageAmerican English
Pages (from-to)17-26
Number of pages10
JournalPharmacology Biochemistry and Behavior
Issue number1
StatePublished - Jan 1989
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by grants MRC MA-6635 awarded to Margaret Brosnan, USPHS NIH NSI1618 and HDO5958 awarded to John Garcia and NSERC A1221 awarded to Mark D. Holder as well as a gift from the David H. Murdock Foundation for Advanced Brain Studies. We wish to thank G. D. Searle and Co. for generously supplying us with aspartame. We also wish to thank Alma Lopez and David Chang for their careful assistance in conducting the behavioral experiments and Barry Waiters for his help in obtaining the blood samples for Experiment 7. We appreciate the expert assistance of Douglas Hall who conducted the amino acid assays reported in Experiment 7.


  • Aspartame
  • Behavioral toxicology
  • Conditioned taste aversion
  • Large neutral amino acids
  • Rat
  • Wheel running


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