Progesterone withdrawal increases the anxiolytic actions of gaboxadol: role of alpha4betadelta GABA(A) receptors.
Hippocampal alpha4betadelta GABA(A) receptors (GABA(A)-R) are increased following progesterone withdrawal (PWD) in a rodent model of premenstrual anxiety. This alpha4betadelta receptor isoform uniquely responds to the GABA agonist gaboxadol (THIP) with a maximum current greater than that gated by GABA, and is potentiated more by pentobarbital than are other GABA(A)-R. We therefore investigated the anxiolytic effects of these drugs using the elevated plus maze. Gaboxadol (1.25 mg/kg) was markedly more anxiolytic in animals undergoing PWD than in controls. Pentobarbital (10 mg/kg) also produced a greater anxiolytic effect during PWD. These results suggest that the pharmacological properties of alpha4betadelta GABA(A)-R following PWD are evident behaviorally. Alterations in the alpha4betadelta GABA(A)-R population may have implications for the etiology and treatment of premenstrual syndrome.
Gulinello
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SUNY Downstate Medical Center, Department of Physiology and Pharmacology, Brooklyn, NY 11203-2098, USA. maria.gulinello@downstate.edu
Gong
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Smith
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004343:Drug Implants; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D018782:Maze Learning / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology / Q000627:therapeutic use; D011293:Premenstrual Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D011374:Progesterone / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D020033:Protein Isoforms / Q000187:drug effects / Q000502:physiology*; D021122:Protein Subunits; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D004343:Drug Implants; D018755:GABA Agonists; D007473:Ion Channels; D007555:Isoxazoles; D020033:Protein Isoforms; D021122:Protein Subunits; D011963:Receptors, GABA-A; D011374:Progesterone; D010424:Pentobarbital; C015542:gaboxadol