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Neuroactive steroids are synthesized de novo in brain, yet their physiological significance remains elusive. We provide biochemical , electrophysiological, and behavioral evidence that several specific actions of alcohol (ethanol) are mediated by the neurosteroid 3␣-hydroxy-5␣-pregnan-20-one (3␣,5␣-THP; allo-pregnanolone). Systemic alcohol administration(More)
The anxiolytic and anticonvulsant effects of benzodiazepines, barbiturates, ethanol and neuroactive steroids are mediated by selective interactions with gamma-aminobutyric acidA (GABA(A)) receptors. Chronic ethanol exposure decreases the sensitivity of GABA(A) receptors to benzodiazepines, barbiturates and ethanol. Ethanol withdrawing rats are(More)
The pharmacological properties of gamma-aminobutyric acidA (GABA(A)) receptors are altered by prolonged exposure to ethanol both in vivo and in vitro. We have shown previously that prolonged ethanol exposure elicits selective alterations in various GABA(A) receptor subunit mRNA levels in rat cerebral cortex. Some of these effects are rapidly reversed during(More)
The molecular mechanisms that underlie ethanol dependence appear to involve alterations in GABAA receptor function and gene expression. In rat cerebral cortex, chronic exposure to ethanol alters many functional properties of GABAA receptors, including reduction of GABAA receptor-mediated chloride uptake. These functional alterations occur without a(More)
Ethanol dependence, arising from chronic ethanol exposure, is associated with neuroadaptations of GABAA receptors, evidenced by alterations in various behaviors, receptor responsiveness and subunit gene expression. The present studies explored the effects of ethanol dependence in female rats for comparison with previous studies in our laboratory using male(More)
Previous research has shown that chronic ethanol consumption dramatically alters GABA(A) receptor alpha1 and alpha4 subunit gene expression in the cerebral cortex and GABA(A) receptor alpha1 and alpha6 subunit gene expression in the cerebellum. However, it is not yet known if chronic ethanol consumption produces similar alterations in GABA(A) receptor gene(More)
BACKGROUND Investigations have shown that chronic ethanol exposure results in selective alterations in levels of gamma-aminobutyric acid (GABA)A and NMDA receptor subunits. We previously reported significant sex differences in these chronic ethanol-induced adaptations. Because we have more recently found important sex differences in timing for the(More)
Previous investigations have shown subunit-selective alterations in NMDA receptors in ethanol dependent male rats. In the present study, we found pronounced gender differences in the effects of ethanol dependence on NMDA receptor subunit expression in all brain regions investigated. Ethanol dependent female rats exhibited increased NR1 subunit levels in(More)
Prolonged alcohol consumption leads to the development of tolerance to and dependence on ethanol, resulting in a decreased response to the sedative/hypnotic effects of ethanol, and by negative symptomatology following abrupt termination of use. One symptom associated with ethanol withdrawal in humans, as well as laboratory animals, is enhanced(More)
Prolonged alcohol (ethanol) consumption leads to the development of alcohol tolerance and cross-tolerance to some benzodiazepines and barbiturates. In contrast, rats undergoing alcohol withdrawal are sensitized to the anticonvulsant effects of the endogenous GABA(A) receptor modulator, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP). Alterations in(More)