Age-dependent effects of methylphenidate in the prefrontal cortex: evidence from electrophysiological and Arc gene expression measurements.
Methylphenidate, a drug widely used for attention deficit hyperactivity disorder in children, may affect neuronal function differently in young and adult subjects, particularly in the prefrontal cortex, a brain structure that does not fully develop until adulthood. We compared the impact of development on the effects of methylphenidate on single unit electrical activity and mRNA expression of the effector immediate early gene activity-regulated cytoskeletal-associated protein (Arc) following methylphenidate in the prefrontal cortex in adult (more than 60 days old) and juvenile (25-35 days old) rats. Methylphenidate, administered under urethane anaesthesia to adult rats, at doses ranging from 1 mg/kg to 3 mg/kg intravenously, exerts a progressive activation of firing of prefrontal cortex neurones (30% to 84% from baseline). This activation was significantly lower in the juvenile rats, reaching only 37% of baseline levels at the highest dose (3 mg/kg, intravenous). In adults, methylphenidate (4 mg/kg intraperitoneal) produced marked increases in Arc mRNA levels compared with saline controls by 123% and 164% in cingulated and orbital cortex, respectively. Corresponding values for the juvenile rats were significantly lower (42% and 79%). In summary, this multi-approach investigation showed that the reactivity of prefrontal cortex neurones to methylphenidate differs markedly in juvenile and adult rats.
Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, UK. bgronier@dmu.ac.uk
Benjamin
B
Gronier
Gronier
G
Benjamin
James
J
Aston
Aston
A
James
Claire
C
Liauzun
Liauzun
L
Claire
Tyra
T
Zetterström
D000367:Age Factors; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D000697:Central Nervous System Stimulants; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein; D008774:Methylphenidate