Behavioral and electrophysiological brain effects of aspartame on well-nourished and malnourished rats

Metab Brain Dis. 2019 Apr;34(2):651-658. doi: 10.1007/s11011-018-0361-9. Epub 2018 Dec 13.


The non-caloric sweetener aspartame can be potentially harmful to the developing brain, as some studies suggest an association between aspartame intake and adverse neural effects. This study aimed to evaluate the possible effects of aspartame, with or without associated early nutritional deficiency, on behavioral parameters suggestive of anxiety and electrophysiological features of the excitability-related phenomenon known as cortical spreading depression (CSD). Newborn Wistar rats (n = 80) were suckled under favorable (L9; n = 40) or unfavorable lactation conditions (L15; n = 40), consisting of litters with 9 or 15 pups, respectively. In each lactation condition, animals were divided into 4 groups that received per gavage, from postnatal day 8 to 28, 75 mg/kg/d or 125 mg/kg/d aspartame (groups ASP75 and ASP125), or water (vehicle group), or no treatment (naive group). Behavioral tests (elevated plus-maze [EPM]) were performed at postnatal days 86-95 and CSD was recorded between postnatal days 96-115. Compared to the control groups, aspartame dose-dependently reduced body weight, suggesting a negative impact on animal development; aspartame also caused behavioral changes suggestive of anxiety (shorter stay in the open arms in the EPM) and decelerated CSD (lower propagation speed). Some of these parameters were more affected in L15 animals, suggesting an interaction among aspartame and lactation condition. We concluded that early consumption of aspartame adversely affects development of the organism (weight loss), with actions on behavioral (anxiety-like) and cerebral electrophysiological (CSD) parameters. The data suggest caution in aspartame consumption by lactating mothers and their infants.

Keywords: Anxiety; Aspartame; Brain excitability; Lactation conditions; Nervous system; Spreading depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Anxiety / drug therapy
  • Aspartame / pharmacology*
  • Behavior, Animal / drug effects*
  • Body Weight / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Cortical Spreading Depression / drug effects
  • Electrophysiological Phenomena / drug effects*
  • Electrophysiological Phenomena / physiology
  • Lactation / physiology
  • Male
  • Rats, Wistar


  • Aspartame