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

• Published in: Biomolecules & therapeutics 2016, 24(2), , pp.115-122
• Main Authors: Hong, Sa-Ik, Kwon, Seung-Hwan, Hwang, Ji-Young, Ma, Shi-Xun, Seo, Jee-Yeon, Ko, Yong-Hyun, Kim, Hyoung-Chun, Lee, Seok-Yong, Jang, Choon-Gon
• Format: Article
• Language: English
• Subjects: Original; 약학
• ISSN: 1976-9148; 2005-4483; 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2015.097

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 significantl. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findingssuggest that modulation of D2-like receptors might enhance the effect of MT on sleep.