title: Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice.
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 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Sa-Ik
authors.initials: SI
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Shi-Xun
authors.initials: SX
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Jee-Yeon
authors.initials: JY
authors.lastname: Seo
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Yong-Hyun
authors.initials: YH
authors.lastname: Ko
authors.affiliation: Neurotoxicology Program, College of Pharmacy, Korea Institute of Drug Abuse, Kangwon National University, Chunchon 24341, Republic of Korea.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
keywords: Dopamine 2 receptor; Melatonin; Pentobarbital; Quinpirole; Sleep