Rahul T. Khisti

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Systemic ethanol administration elevates plasma and brain levels of GABAergic neuroactive steroids, including 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) that contribute to specific behavioral actions of ethanol. The present study determined the effect of adrenalectomy and 5alpha-reductase type-1/type-2 enzyme inhibition, known to reduce(More)
The present study aimed to examine the antidepressant-like effect of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha, 5alpha THP) using the forced swim test in mice. Intracerebroventricular (ICV, 1 or 2 microg/mouse) or intraperitoneal (IP, 0.5, 1, or 2 mg/kg) administration of 3alpha, 5alpha THP dose-dependently reduced the duration of(More)
The present study demonstrated the antidepressant-like effect of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha, 5alpha THP) in mouse forced swim test of depression and its modulation by different serotonergic agents. Pretreatment with the selective serotonin reuptake inhibitor, fluoxetine (5 mg/kg, i.p.), the 5-HT releaser, fenfluramine (10(More)
Ethanol is known to increase cortical and plasma content of GABAergic neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) which is responsible for some of its behavioral and electrophysiological effects. We have previously demonstrated the antidepressant like effect of 3alpha,5alpha-THP in mice. This study investigated the role of(More)
Ethanol craving plays a major role in relapse drinking behavior. Relapse and ethanol craving are an important focus for the treatment of alcoholism. The ethanol-deprivation effect (EDE) is a widely used animal model of alcohol craving. While the EDE is widely studied in rats, the molecular mechanisms underlying EDE are not clearly understood. The C57BL/6(More)
GABAA receptors are an important site of action of endogenous neurosteroids and an important mediator of several behavioral effects of alcohol. This study examined the effects of alcohol on plasma steroid hormone concentrations on the hypothesis that the endocrine effects mediate some of the subjective effects of alcohol. Thirty-two healthy subjects (17(More)
Systemic ethanol administration is known to elevate levels of the GABAergic neuroactive steroid 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THDOC). 3alpha,5alpha-THDOC is synthesized from deoxycorticosterone (DOC) by metabolism in adrenals and brain. The present study investigated DOC levels in plasma and brain following ethanol administration(More)
Olanzapine and fluoxetine elevate the GABAergic neuroactive steroid allopregnanolone to physiologically relevant concentrations in rodent cerebral cortex. It is unknown if these agents also alter pregnenolone or deoxycorticosterone. Since olanzapine and fluoxetine in combination have clinical utility and may demonstrate synergistic effects, we investigated(More)
Protein kinase C (PKC) modulation of ionotropic receptors is a common mechanism for regulation of channel function. The effects of PKC and phosphatase activation on native gamma-aminobutyric acid (GABAA) receptors in adult brain are unknown. Previous studies of recombinant GABAA receptors have provided evidence that PKC activation inhibits receptor(More)
This article summarizes the proceedings of a symposium held at the 2005 Research Society on Alcoholism meeting. The initial presentation by Dr. Wallner provided evidence that selected GABA(A) receptors containing the delta subunit display sensitivity to low intoxicating ethanol concentrations and this sensitivity is further increased by a mutation in the(More)