Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood.
BACKGROUND
Methylphenidate (MPH) is a psychomotor stimulant medication widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Given the extent of prescribed use of MPH, and because MPH interacts with the same brain pathways activated by drugs of abuse, most research has focused on assessing MPH's potential to alter an individual's risk for adult drug addiction. Data examining other potential long-term behavioral consequences of early MPH administration are lacking, however.


METHODS
We investigated the long-term behavioral consequences of chronic administration of MPH (2.0 mg/kg) during pre- and periadolescent development in adult rats by assessing their behavioral reactivity to a variety of emotional stimuli.


RESULTS
The MPH-treated animals were significantly less responsive to natural rewards such as sucrose, novelty-induced activity, and sex compared with vehicle-treated control animals. In contrast, MPH-treated animals were significantly more sensitive to stressful situations, showed increased anxiety-like behaviors, and had enhanced plasma levels of corticosterone.


CONCLUSIONS
Chronic exposure to MPH during development leads to decreased sensitivity to rewarding stimuli and results in enhanced responsivity to aversive situations. These results highlight the need for further research to improve understanding of the effects of stimulants on the developing nervous system and the potential enduring effects resulting from early-life drug exposure.
Bolaños
Carlos A
CA
Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
Barrot
Michel
M
Berton
Olivier
O
Wallace-Black
Deanna
D
Nestler
Eric J
EJ
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects*; D015169:Colony Count, Microbial / Q000379:methods; D003345:Corticosterone / Q000097:blood; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D004644:Emotions / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005518:Food Preferences / Q000187:drug effects; D006120:Grooming / Q000187:drug effects; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D012725:Sexual Behavior / Q000187:drug effects; D012919:Social Behavior; D013395:Sucrose; D013550:Swimming; D013995:Time; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate; D013395:Sucrose; D003345:Corticosterone