Document Type
Journal ArticlePublication Date
2005-11-01Keywords
AnimalsAntioxidants
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Electric Stimulation
Excitatory Postsynaptic Potentials
Hippocampus
Isoquinolines
Long-Term Potentiation
Male
Melatonin
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Kinase Inhibitors
Receptor, Melatonin, MT1
Receptor, Melatonin, MT2
Sulfonamides
Synaptic Transmission
Tryptamines
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
The goal of this study is to investigate the effect of the hormone melatonin on long-term potentiation and excitability measured by stimulating the Schaffer collaterals and recording the field excitatory postsynaptic potential from the CA1 dendritic layer in hippocampal brain slices from mice. Application of melatonin produced a concentration-dependent inhibition of the induction of long-term potentiation, with a concentration of 100 nm producing an approximately 50% inhibition of long-term potentiation magnitude. Long-duration melatonin treatments of 6 h were also effective at reducing the magnitude of long-term potentiation. Melatonin (100 nm) did not alter baseline evoked responses or paired-pulse facilitation recorded at this synapse. The inhibitory actions of melatonin were prevented by application of the melatonin (MT) receptor antagonist luzindole as well as the MT2 receptor subtype antagonist 4-phenyl-2-propionamidotetraline. These inhibitory actions of melatonin were lost in mice deficient in MT2 receptors but not those deficient in MT1 receptors. In addition, application of the protein kinase A inhibitor H-89 both mimicked the effects of melatonin and precluded further inhibition by melatonin. Finally, the application an activator of adenylyl cyclase, forskolin, overcame the inhibitory effects of melatonin on LTP without affecting the induction of long-term potentiation on its own. These results suggest that hippocampal synaptic plasticity may be constrained by melatonin through a mechanism involving MT2-receptor-mediated regulation of the adenylyl cyclase-protein kinase A pathway.Source
Eur J Neurosci. 2005 Nov;22(9):2231-7. Link to article on publisher's siteDOI
10.1111/j.1460-9568.2005.04408.xPermanent Link to this Item
http://hdl.handle.net/20.500.14038/38036PubMed ID
16262661Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1111/j.1460-9568.2005.04408.x