Appetitive-based learning in rats: Lack of effect of chronic exposure to fluoride

Gary M. Whitford, Jennifer L. Whitford, Stephen H. Hobbs

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background: Chronic ingestion of optimally fluoridated water (ca. 1.0 mg/L) has not been associated with any adverse health effects. Possible effects on the nervous system, however, have received little attention. One study with rats given high doses of fluoride reported subtle behavioral changes. The authors suggested that the ability of humans to learn might be reduced and recommended further study with humans and rats. The present study was done to provide data with which to assess this suggestion. Methods: Weanling, female rats (n = 32) were provided with water containing graded doses of fluoride (0, 2.9, 5.7, 11.5 mg/kg body weight/day) for eight months. While under restricted food access they were tested for their ability to learn an operant response for food and to adjust their responding under schedules of reinforcement requiring high rates of responding (5 days) and then low rates of responding (10 days). Bone, plasma and seven regions of brain were analyzed for fluoride. Results: There were no significant differences among the groups in learning or performance of the operant tasks. Tissue fluoride concentrations were directly related to the levels of exposure. In the 11.5 mg/kg/day group the bone, plasma and brain concentrations were 99, 305 and 221 times higher, respectively, than those in the control group. The average brain-to-plasma fluoride concentration ratios in each of the seven brain sections fell within a narrow range and did not exceed 0.40. There was no consistent evidence for the preferential uptake of fluoride by any given brain section. Conclusion: Chronic ingestion of fluoride at levels up to 230 times more than that experienced by humans whose main source of fluoride is fluoridated water had no significant effect on appetitive-based learning.

Original languageEnglish (US)
Pages (from-to)210-215
Number of pages6
JournalNeurotoxicology and Teratology
Issue number4
StatePublished - Jul 1 2009


  • Brain
  • Fluoride
  • Learning

ASJC Scopus subject areas

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience


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