Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice

• Published in: Behavioural brain research Vol. 328; pp. 227 - 234
• Main Authors: Yamaguchi, Takeshi, Nagasawa, Mao, Ikeda, Hiromi, Kodaira, Momoko, Minaminaka, Kimie, Chowdhury, Vishwajit S., Yasuo, Shinobu, Furuse, Mitsuhiro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2017
• Subjects: Analysis of Variance; Animals; BH4; Brain - drug effects; Brain - metabolism; Dopamine - metabolism; Dopamine Agents - pharmacology; Dose-Response Relationship, Drug; L-DOPA; Levodopa - pharmacology; Locomotor activity; Male; Mice; Mice, Inbred C57BL - metabolism; Mice, Inbred CBA - metabolism; Mice, Inbred ICR - metabolism; Motor Activity - drug effects; Motor Activity - physiology; Species Specificity; Dopamine metabolism; Mice; Locomotor activity; L-DOPA; BH4; BH
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2017.04.001

•ICR mice showed higher locomotor activity compared with C57BL/6J and CBA/N mice.•DA content in the cerebellum and striatum was lower in ICR than in C57BL/6J mice.•BH4 administration increased the DA or DA metabolite in some brain regions.•The DA metabolism enhanced by L-DOPA administration attenuated locomotor activity.•The innate high locomotor activity may be explained partly by dopaminergic system. 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 BH4 administration, 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.