Methylphenidate to adolescent rats drives enduring changes of accumbal Htr7 expression: implications for impulsive behavior and neuronal morphology

Genes Brain Behav. 2009 Apr;8(3):356-68. doi: 10.1111/j.1601-183X.2009.00486.x. Epub 2009 Feb 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Cell Enlargement / drug effects
  • Cells, Cultured
  • Central Nervous System Stimulants / pharmacology
  • Disease Models, Animal
  • Female
  • Impulsive Behavior / metabolism
  • Impulsive Behavior / physiopathology*
  • Male
  • Methylphenidate / pharmacology*
  • Neurites / drug effects
  • Neurites / metabolism
  • Neurites / ultrastructure
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Reward
  • Serotonin / metabolism
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology

Substances

  • Central Nervous System Stimulants
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • serotonin 7 receptor
  • Methylphenidate
  • Serotonin