Juvenile Administration of Methylphenidate Attenuates Adult Hippocampal Neurogenesis

• Published in: Biological psychiatry (1969) Vol. 60; no. 10; pp. 1121 - 1130
• Main Authors: Lagace, Diane C., Yee, Jessica K., Bolaños, Carlos A., Eisch, Amelia J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.11.2006; Elsevier Science
• Subjects: ADHD; Analysis of Variance; Animals; Animals, Newborn; Behavior, Animal - drug effects; Biological and medical sciences; BrdU; Bromodeoxyuridine - metabolism; Cell Proliferation - drug effects; Central Nervous System Stimulants - pharmacology; development; Female; hippocampus; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - growth & development; Immunohistochemistry - methods; Male; Medical sciences; Methylphenidate - pharmacology; Neurons - drug effects; Neuropharmacology; Organogenesis - drug effects; Pharmacology. Drug treatments; Photic Stimulation - adverse effects; Pregnancy; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; psychostimulant; Rats; Ritalin; Stress, Psychological - drug therapy; Stress, Psychological - pathology; Time Factors; ADHD; Ritalin; development; hippocampus; BrdU; psychostimulant; Human; CNS stimulant; Hyperactivity; Psychotropic; Central nervous system; psycho- stimulant; Neurogenesis; Encephalon; Chemotherapy; Treatment; Attentional disorder; Piperidine derivatives; Development; Adult; Attention disorder with hyperactivity; Hippocampus; Methylphenidate
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.04.009

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. 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. 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. 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.