Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice.
10.4062/biomolther.2015.097
- Author:
Sa Ik HONG
1
;
Seung Hwan KWON
;
Ji Young HWANG
;
Shi Xun MA
;
Jee Yeon SEO
;
Yong Hyun KO
;
Hyoung Chun KIM
;
Seok Yong LEE
;
Choon Gon JANG
Author Information
1. Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. jang@skku.edu
- Publication Type:Original Article
- Keywords:
Sleep;
Dopamine 2 receptor;
Quinpirole;
Melatonin;
Pentobarbital
- MeSH:
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*
- From:Biomolecules & Therapeutics
2016;24(2):115-122
- CountryRepublic of Korea
- Language:English
-
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.
