The effects of adolescent methylphenidate self-administration on responding for a conditioned reward, amphetamine-induced locomotor activity, and neuronal activation.
BACKGROUND
Abuse of methylphenidate (Ritalin) is rising, particularly during adolescence and early adulthood, but the long-term effects of its abuse during adolescence are unclear.


METHODS
In experiment 1, we examined the effect of adolescent methylphenidate self-administration (0.0625 mg/infusion), as compared with cocaine self-administration (0.125 mg/infusion), under a fixed ratio 1 schedule of reinforcement in male Sprague-Dawley rats during adolescence (postnatal day (PND) 32-47) on adult dopamine-mediated behaviors (PND >70). These included responding for a conditioned reward (CR), a measure of incentive motivation, and amphetamine-induced locomotor activity. In experiment 2, we aimed to replicate and enhance the effects observed in experiment 1, and we also examined the effects of methylphenidate self-administration during adolescence on adult amphetamine-induced zif268 messenger ribonucleic acid (mRNA) expression.


RESULTS
Adolescent rats self-administered both cocaine and methylphenidate. There was no effect of adolescent drug self-administration on adult baseline or amphetamine-induced responding for a CR. However, both adolescent methylphenidate and cocaine self-administration increased amphetamine-induced locomotion. Adolescent methylphenidate self-administration also enhanced amphetamine-induced zif268 mRNA expression in the nucleus accumbens.


CONCLUSIONS
Our findings suggest that repeated, behaviorally contingent exposure to methylphenidate during adolescence enhances responsivity to the locomotor-stimulating and neuronal activating effects of amphetamine but not incentive motivation.
Burton
Christie L
CL
Department of Psychology, University of Toronto, 100 St. George Street, Toronto, ON M5S3G3, Canada. c.burton@utoronto.ca
Nobrega
José N
JN
Fletcher
Paul J
PJ
D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration
D000697:Central Nervous System Stimulants; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D012333:RNA, Messenger; D008774:Methylphenidate; D000661:Amphetamine; D003042:Cocaine