title: Methylphenidate and venlafaxine attenuate locomotion in spontaneously hypertensive rats, an animal model of attention-deficit/hyperactivity disorder, through α2-adrenoceptor activation.
abstract: Recent clinical studies have shown that serotonin-norepinephrine reuptake inhibitors such as venlafaxine and duloxetine are effective against symptoms of attention-deficit/hyperactivity disorder such as inattention, oppositionality, and hyperactivity. We have recently found that these serotonin-norepinephrine reuptake inhibitors, like methylphenidate, reduced the hyperactivity in spontaneously hypertensive rats (SHR), an animal model of attention-deficit/hyperactivity disorder. The present study investigated whether the α2-adrenoceptor and the dopamine-D1 receptor are involved in the behavioral effects of methylphenidate and venlafaxine in SHR. Adolescent male SHR showed greater horizontal locomotion in a familiar open field than male Wistar Kyoto and Wistar rats, and methylphenidate (0.3 mg/kg) and venlafaxine (30 mg/kg) reduced horizontal locomotion in SHR, but not Wistar Kyoto or Wistar rats. The effects of methylphenidate and venlafaxine were blocked by idazoxan (an α2-adrenoceptor antagonist), but not by SCH23390 (a dopamine-D1 receptor antagonist). These findings suggest that the α2-adrenoceptor plays a key role in the effects of methylphenidate and venlafaxine on enhanced locomotion in SHR.
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences.
authors.forename: Masato
authors.initials: M
authors.lastname: Umehara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.forename: Takuya
authors.initials: T
authors.lastname: Kawanai
authors.forename: Kazumi
authors.initials: K
authors.lastname: Fujita
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013997:Time Factors; D000069470:Venlafaxine Hydrochloride
chemical_list: D018663:Adrenergic Agents; D018687:Antidepressive Agents, Second-Generation; D000697:Central Nervous System Stimulants; D003511:Cyclohexanols; D018341:Receptors, Adrenergic, alpha-2; D008774:Methylphenidate; D000069470:Venlafaxine Hydrochloride