Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis.
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.
Lagace
Diane C
DC
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Yee
Jessica K
JK
Bolaños
Carlos A
CA
Eisch
Amelia J
AJ
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D038081:Organogenesis / Q000187:drug effects*; D010775:Photic Stimulation / Q000009:adverse effects; D011247:Pregnancy; D051381:Rats; D013315:Stress, Psychological / Q000188:drug therapy / Q000473:pathology; D013997:Time Factors
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D001973:Bromodeoxyuridine