title: Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice.
abstract: Acute administration of atomoxetine and methylphenidate, attention-deficit/hyperactivity disorder (ADHD) drugs, activates catecholaminergic systems in rat brain, but the effects of their chronic administration are not known. This study examined the effects of acute and chronic administration of ADHD drugs on the extracellular levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT), and the expression of the neuronal activity marker c-Fos in the prefrontal cortex and striatum of mice. Acute ADHD drugs increased NA and DA, but not 5-HT, levels in the prefrontal cortex of mice. Maximal effects of atomoxetine and methylphenidate were observed at 1 mg/kg and 3 mg/kg, respectively. At these doses, both drugs did not affect the spontaneous locomotor activity of mice. Chronic administration of atomoxetine 1 mg/kg and methylphenidate 3 mg/kg for 21 days also increased NA and DA, but not 5-HT, levels in the prefrontal cortex. The increases in NA levels induced by atomoxetine, but not methylphenidate, were reduced by chronic treatment. In contrast, acute and chronic administration of atomoxetine 1 mg/kg and methylphenidate 3 mg/kg did not affect the monoamine levels in the striatum. Acute and chronic atomoxetine 1 mg/kg and methylphenidate 3 mg/kg increased the expression of c-Fos in the prefrontal cortex, but not in the striatum, to a similar extent. These results suggest that acute and chronic administration of the ADHD drugs selectively activate the prefrontal catecholamine systems in mice.
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Koda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.forename: Yana
authors.initials: Y
authors.lastname: Cong
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011437:Propylamines / Q000008:administration & dosage / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D018759:Adrenergic Uptake Inhibitors; D015306:Biogenic Monoamines; D018765:Dopamine Uptake Inhibitors; D011437:Propylamines; D016760:Proto-Oncogene Proteins c-fos; D008774:Methylphenidate; D012701:Serotonin; D000069445:Atomoxetine Hydrochloride; D004298:Dopamine; D009638:Norepinephrine