The forced swim test (FST) is commonly employed to test the potency of drugs to reduce immobility as an indicator of anti-despair. Certainly, antidepressant drugs reduce the total time of immobility and enlarge the latency to the first immobility period. FST is preceded by the open field test (OFT) to discard any influence of changes in general motor activity that could interfere with immobilit...

Posttraumatic stress disorder (PTSD) is a severe condition resulting from exposure to traumatic events, such as combat situations, sexual assault, serious injury or the threat of death. Symptoms include disturbing recurring flashbacks, avoidance or numbing of memories of the event, and hyperarousal, which continue for more than a month after the traumatic event. Reduced cortical GABA (Kugaya et...

Twelve neuroactive and neuroprotective steroids, androgens and androgen precursors i.e. 3alpha,17beta-dihydroxy-5alpha-androstane, 3alpha-hydroxy-5alpha-androstan-17-one, 3alpha-hydroxy-5beta-androstan-17-one, androst-5-ene-3beta,17beta-diol, 3beta,17alpha-dihydroxy-pregn-5-en-20-one (17alpha-hydroxy-pregnenolone), 3beta-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, ...

Rat cerebellar granule cells were cultured for 5 days with progesterone, resulting in the conversion of progesterone to allopregnanolone, a potent and efficacious modulator of gamma-aminobutyric acid (GABA) type-A receptors, as well as in decreases in the abundance of GABA(A) receptor alpha(1), alpha(3), alpha(5), and gamma(2) subunit mRNAs. These effects were accompanied by decreases in the ef...

Neuroactive steroids can either potentiate or inhibit a variety of membrane channels. Most studies have suggested that the effects are mediated by specific association of the steroid with the affected channel. However, a recent study of the 1 (GABA-C) receptor (Mol Pharmacol 66:56–69, 2004) concluded that the actions were consistent with an action of the steroid in the lipid bilayer to alter th...

Alterations in GABA(A) receptor (GABA(A)R) expression and function, similar to those we described previously during pregnancy in the mouse dentate gyrus, may also occur in other brain regions. Here we show, using immunohistochemical techniques, a decreased delta subunit-containing GABA(A)R (deltaGABA(A)R) expression in the dentate gyrus, hippocampal CA1 region, thalamus, and striatum but not in...

Perimenstrual catamenial epilepsy, the exacerbation of seizures in association with menstruation, may in part be due to withdrawal of the progesterone metabolite allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), an endogenous anticonvulsant neurosteroid that is a positive allosteric modulator of gamma-aminobutyric acid(A) receptors. Neurosteroid replacement is a potential approach to the...