Selective reduction of gamma-aminobutyric acid type A receptor delta subunit mRNA levels by MK-801 in rat dentate gyrus.
The influence of excitatory blockade elicited by uncompetitive N-methyl-D-aspartate (NMDA)/glutamate receptor antagonists on inhibitory GABAergic systems is not well understood. Adult male rats were injected i.p. with a single dose of the prototypical uncompetitive antagonist MK-801 (0.2-10 mg/kg) and in situ hybridization was performed to measure mRNA levels of gamma-aminobutyric acid type A (GABAA) receptor subunits (alpha1-6, beta1-3, gamma1-3, delta, and theta). A significant decrease in delta subunit mRNA levels, that reached approximately 70% of saline-treated values, was observed in the hippocampal dentate gyrus following MK-801 administration. Other subunits did not display statistically significant alterations. These data demonstrate selective actions on GABAA receptor subunit levels that result from blockade of excitation by MK-801.
Sinkkonen
Saku T
ST
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
Lindén
Anni-Maija
AM
Korpi
Esa R
ER
Wong
Garry
G
D000818:Animals; D001345:Autoradiography; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism*; D003864:Depression, Chemical; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000096:biosynthesis*
D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; C464500:GABRD protein, human; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D016291:Dizocilpine Maleate