Abstract:
:In vitro evidence indicates that norepinephrine release in the mammalian hippocampus is modulated by glutamate receptors. With the use of microdialysis, we have now evaluated the role of ionotropic glutamate receptors in the regulation of hippocampal norepinephrine output in vivo. Stimulation of N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors by local administration of NMDA (1-100μM) resulted in a concentration-dependent decrease in the extracellular concentration of norepinephrine in the hippocampus of freely moving rats, whereas the blockade of these receptors with MK801 (1-100μM) induced a concentration-dependent increase in norepinephrine output. Activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-sensitive glutamate receptors with AMPA (1-100μM) resulted in a biphasic effect on the extracellular norepinephrine concentration, with a decrease in this parameter apparent at 10μM and an increase at 100μM. The AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione had no effect on norepinephrine output. The GABA(A) receptor antagonist bicuculline (10μM) prevented the decrease in hippocampal norepinephrine output induced by either NMDA or 10μM AMPA. Our results thus implicate ionotropic glutamate receptors as key regulators of norepinephrine release in the hippocampus and may therefore provide a basis for the development of new drugs for stress-related disorders.
journal_name
Brain Resjournal_title
Brain researchauthors
Dazzi L,Matzeu A,Biggio Gdoi
10.1016/j.brainres.2011.02.065subject
Has Abstractpub_date
2011-04-22 00:00:00pages
41-9eissn
0006-8993issn
1872-6240pii
S0006-8993(11)00421-5journal_volume
1386pub_type
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