Biomol Ther.  2016 Mar;24(2):115-122. 10.4062/biomolther.2015.097.

Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice

• Hong SI
• Kwon SH
• Hwang JY
• Ma SX
• Seo JY
• Ko YH
• Kim HC
• Lee SY
• Jang CG

• KMID: 2170522
• DOI: http://doi.org/10.4062/biomolther.2015.097

Abstract

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

Keyword

Sleep; Dopamine 2 receptor; Quinpirole; Melatonin; Pentobarbital

MeSH Terms

Animals
Cerebral Cortex
Cyclic AMP-Dependent Protein Kinases
Dopamine
gamma-Aminobutyric Acid
Humans
Hypnotics and Sedatives
Melatonin
Mice*
Mitogen-Activated Protein Kinases
Motor Activity
Neurotransmitter Agents
p38 Mitogen-Activated Protein Kinases*
Pentobarbital*
Phosphotransferases
Protein Kinase C
Protein Kinases
Quinpirole*
Cyclic AMP-Dependent Protein Kinases
Dopamine
Hypnotics and Sedatives
Melatonin
Mitogen-Activated Protein Kinases
Neurotransmitter Agents
Pentobarbital
Phosphotransferases
Protein Kinase C
Protein Kinases
Quinpirole
gamma-Aminobutyric Acid
p38 Mitogen-Activated Protein Kinases