title: Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice.
abstract: Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH4) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH4administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism.
authors.affiliation: Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Nagasawa
authors.affiliation: Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Kodaira
authors.affiliation: Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Kimie
authors.initials: K
authors.lastname: Minaminaka
authors.affiliation: Division for Experimental Natural Science, Faculty of Arts and Science, Kyushu University, Fukuoka 819-0395, Japan.
authors.forename: Vishwajit S
authors.initials: VS
authors.lastname: Chowdhury
authors.affiliation: Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Yasuo
authors.affiliation: Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan. Electronic address: furuse@brs.kyushu-u.ac.jp.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Furuse
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL / Q000378:metabolism; D008808:Mice, Inbred CBA / Q000378:metabolism; D008813:Mice, Inbred ICR / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity
chemical_list: D015259:Dopamine Agents; D007980:Levodopa; D004298:Dopamine
keywords: BH(4); Dopamine metabolism; L-DOPA; Locomotor activity; Mice