Light/dark phase-dependent spontaneous activity is maintained in dopamine-deficient mice

Yukio Takamatsu,Kazuto Kobayashi,Miho Tanaka,Shinya Kasai,Kazutaka Ikeda,Taishi Takeda,Masayo Fujita,Yoko Hagino

doi:10.1186/s13041-017-0329-4

Abstract

Dopamine is important for motor control and involved in the regulation of circadian rhythm. We previously found that dopamine-deficient (DD) mice became hyperactive in a novel environment 72 h after the last injection of L-3,4-dihydroxyphenylalanine (L-DOPA) when dopamine was almost completely depleted. DD mice did not initially exhibit hyperactivity in their home cages, but the animals exhibited hyperactivity several hours after the last L-DOPA injection. The regulation of motor activity in a novel environment and in home cages may be different. A previous study reported that DD mice became active again approximately 24 h after the last L-DOPA injection. One speculation was that light/dark phase-dependent spontaneous activity might be maintained despite dopamine deficiency. The present study investigated whether spontaneous home cage activity is maintained in DD mice 24–43 h and 72–91 h after the last L-DOPA injection. Spontaneous activity was almost completely suppressed during the light phase of the light/dark cycle in DD mice 24 and 72 h after the last L-DOPA injection. After the dark phase began, DD mice became active 24 and 72 h after the last L-DOPA injection. DD mice exhibited a similar amount of locomotor activity as wildtype mice 24 h after the last L-DOPA injection. Although DD mice presented a decrease in activity 72 h after the last L-DOPA injection, they maintained dark phase-stimulated locomotor activation. Despite low levels of dopamine in DD mice, they exhibited feeding behavior that was similar to wildtype mice. Although grooming and rearing behavior significantly decreased, DD mice retained their ability to perform these activities. Haloperidol treatment significantly suppressed all of these behaviors in wildtype mice but not in DD mice. These results indicate that DD mice maintain some aspects of light/dark phase-dependent spontaneous activity despite dopamine depletion, suggesting that compensatory dopamine-independent mechanisms might play a role in the DD mouse phenotype.

Highlights

Dopamine is a neurotransmitter that plays important roles in various behaviors, including motor movement, motivation, reward, and cognition [1,2,3]
DD mice 72 h after the last L-DOPA injection became active after the beginning of the dark phase while the extent of locomotor activity was less than wildtype and DD mice 24 h after the last L-DOPA injection (Fig. 1), indicating that the dark phasedependent increase in locomotor activity remained even with extremely low dopamine levels
DD mice lost more than 1 g of their body weight if L-DOPA injections were skipped for 1 day. These results indicate that DD mice ate their feed they exhibited dopamine depletion, but their food intake was less compared with wildtype mice

Summary

Introduction

Dopamine is a neurotransmitter that plays important roles in various behaviors, including motor movement, motivation, reward, and cognition [1,2,3]. The functions of dopamine are exerted by its release from dopaminergic neurons in the central nervous system. The dopaminergic pathway in the basal ganglia is considered essential for motor movement. In Parkinson’s disease patients, a reduction of dopamine concentrations in the striatum that is caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to motor impairment [5]. The removal of dopaminergic neurons by neurotoxin application leads to motor impairment [6, 7]. The blockade of dopaminergic neurotransmission with dopamine receptor antagonists results in motor impairment [8]. Based on Fujita et al Molecular Brain (2017) 10:49 these observations, dopamine concentrations may be correlated with the extent of locomotor activity

Methods

Results

Conclusion