Altered responsiveness to cocaine in rats exposed to methylphenidate during development.
Evidence in laboratory animals indicates that exposure to stimulants produces sensitization to their rewarding effects, a process that in humans would be expected to increase the risk of substance abuse. However, therapeutic administration of stimulants such as methylphenidate (MPH) in children with attention deficit hyperactivity disorder reportedly reduces the risk of substance abuse. Here we show in rats that exposure to MPH during pre-adolescence causes behavioral and neurobiological adaptations that endure into adulthood, and that are consistent with increased sensitivity to the aversive effects of cocaine.
Andersen
Susan L
SL
Department of Psychiatry, Harvard Medical School and McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02478, USA. andersen@mclean.org
Arvanitogiannis
Andreas
A
Pliakas
Andrea M
AM
LeBlanc
Celeste
C
Carlezon
William A
WA
D000222:Adaptation, Physiological; D000328:Adult; D000375:Aging / Q000502:physiology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002648:Child; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003214:Conditioning, Classical; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006801:Humans; D008774:Methylphenidate / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D012201:Reward; D013997:Time Factors
D000697:Central Nervous System Stimulants; D017362:Cyclic AMP Response Element-Binding Protein; D018091:Receptors, AMPA; D008774:Methylphenidate; D003042:Cocaine; C104722:glutamate receptor ionotropic, AMPA 2