Discriminative stimulus properties of midazolam are shared by a GABA-receptor positive steroid.
3-Alpha-5-alpha-tetrahydrodeoxycorticosterone (alloTHDOC) is a 3-alpha ring A-reduced metabolite of deoxycorticosterone that has been shown to act via nongenomic mechanisms to modulate the GABAA receptor complex allosterically in vitro. Moreover, there are behavioral data consistent with the anxiolytic actions of GABA-receptor positive steroids. The drug discrimination paradigm was used in rats to demonstrate that effects of alloTHDOC are mediated by the GABAA receptor complex in the intact animal. In rats trained to discriminate 1.8 mg/kg of midazolam from saline, alloTHDOC substituted for the training stimulus.
Deutsch
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Psychiatry Service, Department of Veterans Affairs Medical Center, Washington, DC 20422.
Mastropaolo
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J
D000818:Animals; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF; D011963:Receptors, GABA-A / Q000187:drug effects; D013256:Steroids / Q000494:pharmacology*
D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D013256:Steroids; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D008874:Midazolam