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Inhibition of basal and amphetamine-stimulated extracellular signal-regulated kinase (ERK) phosphorylation in the rat forebrain by muscarinic acetylcholine M4 receptors.
- Source :
-
Brain research [Brain Res] 2018 Jun 01; Vol. 1688, pp. 103-112. Date of Electronic Publication: 2018 Mar 22. - Publication Year :
- 2018
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Abstract
- The mitogen-activated protein kinase (MAPK), especially its extracellular signal-regulated kinase (ERK) subfamily, is a group of kinases enriched in the mammalian brain. While ERK is central to cell signaling and neural activities, the regulation of ERK by transmitters is poorly understood. In this study, the role of acetylcholine in the regulation of ERK was investigated in adult rat striatum in vivo. We focused on muscarinic M1 and M4 receptors, two principal muscarinic acetylcholine (mACh) receptor subtypes in the striatum. A systemic injection of the M1-preferring antagonist telenzepine did not alter ERK phosphorylation in the two subdivisions of the striatum, the caudate putamen and nucleus accumbens. Similarly, telenzepine did not affect ERK phosphorylation in the medial prefrontal cortex (mPFC), hippocampus, and cerebellum. Moreover, telenzepine had no effect on the ERK phosphorylation induced by dopamine stimulation with the psychostimulant amphetamine. In contrast to telenzepine, the M4-preferring antagonist tropicamide consistently increased ERK phosphorylation in the striatum and mPFC. This increase was rapid and transient. Tropicamide and amphetamine when coadministered at subthreshold doses induced a significant increase in ERK phosphorylation. These results demonstrate that mACh receptors exert a subtype-specific modulation of ERK in striatal and mPFC neurons. While the M1 receptor antagonist has no effect on ERK phosphorylation, M4 receptors inhibit constitutive and dopamine-stimulated ERK phosphorylation in these dopamine-innervated brain regions.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Brain drug effects
Corpus Striatum drug effects
Corpus Striatum metabolism
Dopamine administration & dosage
Hippocampus drug effects
Hippocampus metabolism
Male
Muscarinic Antagonists administration & dosage
Phosphorylation
Pirenzepine administration & dosage
Pirenzepine analogs & derivatives
Prefrontal Cortex drug effects
Prefrontal Cortex metabolism
Rats, Wistar
Receptor, Muscarinic M1 metabolism
Tropicamide administration & dosage
Amphetamine administration & dosage
Brain metabolism
Central Nervous System Stimulants administration & dosage
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Receptor, Muscarinic M4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1688
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 29577888
- Full Text :
- https://doi.org/10.1016/j.brainres.2018.03.019