Journal
NEUROREPORT
Volume 14, Issue 1, Pages 43-46Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00001756-200301200-00008
Keywords
alpha 4 subunit; allopregnanolone; anxiety; extra-synaptic; delta subunit; GABA(A) receptor; neurosteroid; premenstrual syndrome; progesterone; tonic current
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Funding
- NIAAA NIH HHS [AA 12958, R01 AA012958] Funding Source: Medline
- NIDA NIH HHS [DA09618, R01 DA009618] Funding Source: Medline
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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.
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