Methylphenidate to adolescent rats drives enduring changes of accumbal Htr7 expression: implications for impulsive behavior and neuronal morphology.
Methylphenidate (MPH) administration to adolescent rodents produces persistent region-specific changes in brain reward circuits and alterations of reward-based behavior. We show that these modifications include a marked increment of serotonin (5-hydroxy-tryptamine) receptor type 7 (Htr7) expression and synaptic contacts, mainly in the nucleus accumbens, and a reduction of basal behavioral impulsivity. We show that neural and behavioral consequences are functionally related: administration of a selective Htr7 antagonist fully counteracts the MPH-reduced impulsive behavior and enhances impulsivity when administered alone in naive rats. Agonist-induced activation of endogenous Htr7 significantly increases neurite length in striatal neuron primary cultures, thus suggesting plastic remodeling of neuronal morphology. The mixed Htr (1a/7) agonist, 8-OH-DPAT, reduces impulsive behavior in adolescent rats and in naive adults, whose impulsivity is enhanced by the Htr7 antagonist. In summary, behavioral pharmacology experiments show that Htr7 mediates self-control behavior, and brain primary cultures experiments indicate that this receptor may be involved in the underlying neural plasticity, through changes in neuronal cytoarchitecture.
Leo
D
D
Institute of Genetics and Biophysics A. Buzzati Traverso, CNR, Naples, Naples, Italy.
Adriani
W
W
Cavaliere
C
C
Cirillo
G
G
Marco
E M
EM
Romano
E
E
di Porzio
U
U
Papa
M
M
Perrone-Capano
C
C
Laviola
G
G
D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007175:Impulsive Behavior / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012201:Reward; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D008774:Methylphenidate; D012701:Serotonin