Effect of acute ethanol administration and acute allopregnanolone administration on spontaneous hippocampal pyramidal cell neural activity

Tokunaga, Sayaka; McDaniel, Janelle R.; Morrow, A. Leslie; Matthews, Douglas B.

doi:10.1016/s0006-8993(02)04266-x

Cited by 49 publications

(34 citation statements)

References 41 publications

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“…Ethanol-induced changes in 3a,5a-THP have been shown to alter neurophysiology in the hippocampus. Elegant studies in vivo (Tokunaga et al, 2003) and in vitro (Sanna et al, 2004) suggest that 3a,5a-THP contributes to ethanol's effects on hippocampal CA1 pyramidal cell physiology, including ethanol depression of LTP (Tokuda et al, 2011). In the present study, ethanol increased 3a,5a-THP in the CA1 pyramidal cell layer as well as the polymorphic cell layer of the DG.…”

Section: Discussionsupporting

confidence: 57%

“…ADX or inhibition of 5a-reduced steroid synthesis with the 5a-reductase (5a-R) inhibitor finasteride reduces some of the behavioral effects of ethanol, including the anticonvulsant (VanDoren et al, 2000), antidepressant-like (Hirani et al, 2002), and anxiolytic-like (Hirani et al, 2005) effects in rats. Finasteride also blocks ethanol inhibition of neuron firing in the medial septum (VanDoren et al, 2000), the hippocampus both in vivo (Tokunaga et al, 2003) and in vitro (Sanna et al, 2004), and long-term potentiation (LTP) in hippocampal slices (Tokuda et al, 2011). Importantly, finasteride also reduces the subjective effects of ethanol in men (PierucciLagha et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

Cook

Nelli

Neighbors

et al. 2014

Neuropsychopharmacol

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The neuroactive steroid (3a,5a)-3-hydroxypregnan-20-one (3a,5a-THP or allopregnanolone) is a positive modulator of GABA A receptors synthesized in the brain, adrenal glands, and gonads. In rats, ethanol activates the hypothalamic-pituitary-adrenal axis and elevates 3a,5a-THP in plasma, cerebral cortex, and hippocampus. In vivo, these effects are dependent on both the pituitary and adrenal glands. In vitro, however, ethanol locally increases 3a,5a-THP in hippocampal slices, in the absence of adrenal influence. Therefore, it is not known whether ethanol can change local brain levels of 3a,5a-THP in vivo, independent of the adrenals. To directly address this controversy, we administered ethanol (2 g/kg) or saline to rats that underwent adrenalectomy (ADX) or received sham surgery and performed immunohistochemistry for 3a,5a-THP. In the medial prefrontal cortex (mPFC), ethanol increased 3a,5a-THP after sham surgery, compared with saline controls, with no ethanol-induced change in 3a,5a-THP following ADX. In subcortical regions, 3a,5a-THP was increased independent of adrenals in the CA1 pyramidal cell layer, dentate gyrus polymorphic layer, bed nucleus of the stria terminalis, and paraventricular nucleus of the hypothalamus. Furthermore, ethanol decreased 3a,5a-THP labeling in the nucleus accumbens shore and central nucleus of the amygdala, independent of the adrenal glands. These data indicate that ethanol dynamically regulates local 3a,5a-THP levels in several subcortical regions; however, the adrenal glands contribute to 3a,5a-THP elevations in the mPFC. Using double immunofluorescent labeling we determined that adrenal dependence of 3a,5a-THP induction by ethanol is not due to a lack of colocalization of 3a,5a-THP with the cholesterol transporters steroidogenic acute regulatory protein (StAR) or translocator protein (TSPO).

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

Cook

Nelli

Neighbors

et al. 2014

Neuropsychopharmacol

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“…VanDoren et al (2000) were able to reduce the anticonvulsant action of ethanol and completely block the effect of moderate concentrations of ethanol on medial septal neurons by minimizing the production of neurosteroids with the 5a-reductase inhibitor finasteride. Likewise, Tokunaga et al (2003) demonstrated a reduction of ethanol action on neural activity in the hippocampus by inhibiting neuroactive steroid production. However, finasteride did not affect duration of loss of righting by ethanol (Khisti et al, 2003;VanDoren et al, 2000), possibly because the enzyme blocked by this synthesis inhibitor is localized to specific brain regions not related to this functional measure.…”

Section: Neurosteroid Involvement In the Gabamimetic Profile Of Ethanmentioning

confidence: 97%

A Conceptualization of Integrated Actions of Ethanol Contributing to its GABAmimetic Profile: A Commentary

Criswell

Breese

2005

Neuropsychopharmacol

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Early behavioral investigations supported the contention that systemic ethanol displays a GABAmimetic profile. Microinjection of GABA agonists into brain and in vivo electrophysiological studies implicated a regionally specific action of ethanol on GABA function. While selectivity of ethanol to enhance the effect of GABA was initially attributed an effect on type-1-benzodiazepine (BZD)-GABA A receptors, a lack of ethanol's effect on GABA responsiveness from isolated neurons with this receptor subtype discounted this contention. Nonetheless, subsequent work identified GABA A receptor subtypes, with limited distribution in brain, sensitive to enhancement of GABA at relevant ethanol concentrations. In view of these data, it is hypothesized that the GABAmimetic profile for ethanol is due to activation of mechanisms associated with GABA function, distinct from a direct action on the majority of postsynaptic GABA A receptors. The primary action proposed to account for ethanol's regional specificity on GABA transmission is its ability to release GABA from some, but not all, presynaptic GABAergic terminals. As systemic administration of ethanol increases neuroactive steroids, which can enhance GABA responsiveness, this elevated level of neurosteroids is proposed to magnify the effect of GABA released by ethanol. Additional factors contributing to the degree to which ethanol interacts with GABA function include an involvement of GABA B and other receptors that influence ethanol-induced GABA release, an effect of phosphorylation on GABA responsiveness, and a regional reduction of glutamatergic tone. Thus, an integration of these consequences induced by ethanol is proposed to provide a logical basis for its in vivo GABAmimetic profile.

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“…Importantly, administration of the immediate precursor of 3a,5a-THP restores effects of ethanol in adrenalectomized animals, showing that brain synthesis of neuroactive steroids modulates effects of ethanol (Khisti et al, 2003). Additionally, VanDoren et al (2000) were able to block the effects of moderate concentrations of ethanol on medial septal neurons and Tokunaga et al (2003) demonstrated a reduction of ethanol activity in the hippocampus by minimizing the production of neurosteroids. Taken together, these studies suggest that elevations in neuroactive steroids are responsible for many of the GABAergic effects of ethanol in vivo and the effects of neuroactive steroids may determine sensitivity to the behavioral effects of ethanol.…”

Section: Behavioral and Functional Effects Of Ethanol Modulated By Enmentioning

confidence: 99%

Basis of the Gabamimetic Profile of Ethanol

Breese¹,

Criswell²,

Carta

et al. 2006

Alcoholism Clin & Exp Res

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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 cerebellar alpha6 subunit, found in alcohol-hypersensitive rats. Dr. Mameli reported that ethanol affects gamma-aminobutyric acid (GABA) function by affecting neural circuits that influence GABA release. Dr. Parsons presented data from electrophysiological and microdialysis investigations that ethanol is capable of releasing GABA from presynaptic terminals. Dr. Morrow demonstrated that systemic ethanol increases neuroactive steroids in brain, the absence of which alters various functional responses to ethanol. Dr. Criswell presented evidence that the ability of ethanol to increase GABA was apparent in some, but not all, brain regions indicative of regional specificity. Further, Dr. Criswell demonstrated that neurosteroids alone and when synthesized locally by ethanol act postsynaptically to enhance the effect of GABA released by ethanol in a region specific manner. Collectively, this series of reports support the GABAmimetic profile of acutely administered ethanol being dependent on several specific mechanisms distinct from a direct effect on the major synaptic isoforms of GABA(A) receptors.

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Effect of acute ethanol administration and acute allopregnanolone administration on spontaneous hippocampal pyramidal cell neural activity

Cited by 49 publications

References 41 publications

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

A Conceptualization of Integrated Actions of Ethanol Contributing to its GABAmimetic Profile: A Commentary

Basis of the Gabamimetic Profile of Ethanol

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