Juvenile Administration of Methylphenidate Attenuates Adult Hippocampal Neurogenesis

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

Research output: Contribution to journalArticle

64 Citations (Scopus)

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

Fingerprint

Methylphenidate
Neurogenesis
Cell Proliferation
Corticosterone
Hippocampus
5,10-dihydro-5-methylphenazine
Cell Survival
Newborn Infant
Neurons
Survival

Keywords

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

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Juvenile Administration of Methylphenidate Attenuates Adult Hippocampal Neurogenesis. / Lagace, Diane C.; Yee, Jessica K.; Bolaños, Carlos A.; Eisch, Amelia J.

In: Biological Psychiatry, Vol. 60, No. 10, 15.11.2006, p. 1121-1130.

Research output: Contribution to journalArticle

Lagace, Diane C. ; Yee, Jessica K. ; Bolaños, Carlos A. ; Eisch, Amelia J. / Juvenile Administration of Methylphenidate Attenuates Adult Hippocampal Neurogenesis. In: Biological Psychiatry. 2006 ; Vol. 60, No. 10. pp. 1121-1130.
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