Methylphenidate amplifies long-term plasticity in the hippocampus via noradrenergic mechanisms.
Methylphenidate treatment is used for Attention Deficit Hyperactivity Disorder and can improve learning and memory. Previously, improvements were considered a by-product of increased attention; however, we hypothesize that methylphenidate directly alters mechanisms underlying learning and memory, and therefore examined its effects on hippocampal long-term potentiation and long-term depression. Methylphenidate enhanced both mechanisms in the absence of presynaptic changes and in a noradrenalin beta-receptor-dependent manner. These findings can explain both the improved learning and memory and decreased learning selectivity found with methylphenidate treatment and constitute the first demonstration of direct actions of methylphenidate on mechanisms implicated in cognition.
Dommett
Eleanor J
EJ
Department of Pharmacology, Oxford University, Mansfield Road, Oxford OX1 3QT, United Kingdom. Eleanor.dommett@pharm.ox.ac.uk
Henderson
Emma L
EL
Westwell
Martin S
MS
Greenfield
Susan A
SA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013999:Timolol / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D013999:Timolol; D009638:Norepinephrine