Juvenile Administration of Methylphenidate Attenuates Adult Hippocampal Neurogenesis

Diane C. Lagace, Jessica K. Yee, Carlos A. Bolaños, Amelia J. Eisch

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Background: The neural consequences of early-life exposure to methylphenidate (MPH; Ritalin) are of great interest given the widespread, and sometimes inappropriate, use in children. Here we examine the impact of juvenile MPH exposure on adult hippocampal neurogenesis. Methods: Rats received MPH (2.0 mg/kg, intraperitoneal, twice daily) or saline (SAL) during preadolescence (postnatal days 20-35). Hippocampal cell proliferation (Experiment 1), neurogenesis (Experiment 2), and stress-induced changes in cell proliferation (Experiment 3) were assessed at several developmental stages including adulthood. Results: Juvenile exposure to MPH did not alter proliferation at any developmental time point relative to control rats; however, exposure to MPH significantly decreased the long-term survival of newborn cells in adult rats, particularly in the temporal hippocampus. Although MPH-treated rats had higher levels of corticosterone after restraint stress, they did not show the expected greater decrease in hippocampal cell proliferation relative to control animals. Conclusions: Early-life exposure to MPH inhibits the survival of adult-generated neurons in the temporal hippocampus and may reduce progenitor sensitivity to corticosterone-induced decreases in proliferation. These findings suggest that decreased adult neurogenesis is an enduring consequence of early-life exposure to MPH and are discussed for their relevance to humans.

Original languageEnglish (US)
Pages (from-to)1121-1130
Number of pages10
JournalBiological Psychiatry
Volume60
Issue number10
DOIs
StatePublished - Nov 15 2006

Keywords

  • ADHD
  • BrdU
  • Ritalin
  • development
  • hippocampus
  • psychostimulant

ASJC Scopus subject areas

  • Biological Psychiatry

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