scholarly journals The Role of Alcohol in Hippocampal Calcium Channel (Cav1.2) expression

2020 ◽  
Vol 3 ◽  
Author(s):  
Ryan Kokoska ◽  
Eric Rodriguez ◽  
Bryan Yamamoto
Keyword(s):  
Calcium Signaling ◽  
Regional Distribution ◽  
Alcohol Exposure ◽  
Chronic Alcoholism ◽  
Ethanol Exposure ◽  
Sprague Dawley ◽  
Memory And Learning ◽  
Disease States ◽  
Stratum Pyramidale ◽  
Sprague Dawley Rats

Background and Hypothesis:   Voltage-gated L-type calcium channels (Cav1.2 and Cav1.3) in the hippocampus play important roles in glutamatergic neurotransmission underlying memory and learning. Their overexpression has been implicated in neuroexcitatory cell death and disease states including chronic alcoholism. While increases in Cav1.2 gene expression have been reported in the hippocampus after chronic ethanol exposure in rats, the regional distribution of Cav1.2 protein after voluntary ethanol (EtOH) drinking has not been reported. We hypothesize that the expression of Cav1.2 channels within the hippocampus is increased by EtOH drinking in a region-specific manner.    Methods:  Male Sprague Dawley rats were allowed 28 days of intermittent access to a 10% EtOH solution.  At 24 hours after the last exposure to EtOH, brains were collected and processed for immunohistochemistry. Cav1.2 associated immunofluorescent signal from subregions of the hippocampus was quantified using ImageJ analysis software.     Results:  Immunohistochemical results indicate that Cav1.2 immunoreactivity in the hippocampal stratum granulosum layer within the Dentate Gyrus and the stratum pyramidale layer within CA1 and CA3 regions was increased in response to EtOH treatment. There was no significant change in Cav1.2 immunoreactivity for the CA2 region.     Conclusion:   This study suggests that calcium signaling in subregions of the hippocampus is differentially affected by EtOH consumption that may contribute to eventual calcium-mediated apoptosis.    Impact and Implications:  Understanding the process of EtOH-induced hippocampal calcium signaling presents opportunities for understanding the consequences of chronic alcohol exposure related to hippocampal function including memory and learning, and possible interventional therapies for alcohol damage.  

Systemic CI-966, a new γ-aminobutyric acid uptake blocker, enhances γ-aminobutyric acid action in CA1 pyramidal layer in situ

1990 ◽  
Vol 68 (9) ◽  
pp. 1194-1199 ◽  
Author(s):  
U. Ebert ◽  
K. Krnjević
Keyword(s):  
Aminobutyric Acid ◽  
Gaba Uptake ◽  
Acid Uptake ◽  
Sprague Dawley ◽  
Nipecotic Acid ◽  
Ca1 Region ◽  
Stratum Pyramidale ◽  
Sprague Dawley Rats ◽  
Pyramidal Layer ◽  
Urethane Anaesthesia

A new potent, blood–brain barrier permeable γ-aminobutyric acid (GABA) uptake blocker, 1-[2-[bis[4-(trifluoromethyl)-phenyl]methoxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (CI-966) was administered systemically by i.p. injection (5 mg/kg) in Sprague–Dawley rats under urethane anaesthesia. Twenty to thirty minutes after injection there was a highly variable, but overall significant, enhancement of the inhibition of hippocampal population spikes by GABA applied by microiontophoresis in the CA1 region. Like the effect of nipecotic acid (applied locally by iontophoresis), the potentiation by CI-966 was clearest when GABA was applied in or near the stratum pyramidale where its action normally is weakest and shows the most pronounced fading. This change in GABA potency is most simply explained by a reduction in GABA uptake.Key words: GABA, muscimol, nipecotic acid, GABA-uptake blocker, epilepsy.

scholarly journals Moderate Adolescent Ethanol Vapor Exposure and Acute Stress in Adulthood: Sex-Dependent Effects on Social Behavior and Ethanol Intake in Sprague–Dawley Rats

2020 ◽  
Vol 10 (11) ◽  
pp. 829
Author(s):  
Meredith E. Gamble ◽  
Marvin R. Diaz
Keyword(s):  
Alcohol Use ◽  
Social Preference ◽  
Stress Reactivity ◽  
Acute Stress ◽  
Ethanol Vapor ◽  
Ethanol Exposure ◽  
Ethanol Intake ◽  
Sprague Dawley ◽  
Long Term Effects ◽  
Sprague Dawley Rats

Adolescent alcohol use can lead to numerous consequences, including altered stress reactivity and higher risk for later anxiety and alcohol use disorders. Many studies have examined the consequences of heavy ethanol exposure in adolescence, but far less is understood about lower levels of intoxication. The present study examined moderate adolescent ethanol exposure as a possible factor in increasing stress reactivity in adulthood, measured through general and social anxiety-like behaviors, as well voluntary ethanol intake. Male and female Sprague–Dawley rats underwent an adolescent chronic intermittent ethanol (aCIE) vapor exposure during early adolescence, reaching moderate blood ethanol concentrations. Animals then underwent two days of forced swim stress in adulthood. We found that ethanol-exposed males consumed more ethanol than their air counterparts and an interesting stress and ethanol exposure interaction in males. There were no significant effects on voluntary drinking in females. However, the social interaction test revealed increased play-fighting behavior in ethanol-exposed females and reduced social preference in females after two days of stress exposure. Overall, this work provides evidence for sex-specific, long-term effects of moderate aCIE and susceptibility to acute stress in adulthood.

scholarly journals 7,8-Dihydroxyflavone Enhances Cue-Conditioned Alcohol Reinstatement in Rats

2020 ◽  
Vol 10 (5) ◽  
pp. 270 ◽  
Author(s):  
Samuel J. Hogarth ◽  
Elvan Djouma ◽  
Maarten van den Buuse
Keyword(s):  
Body Weight ◽  
Progressive Ratio ◽  
Ethanol Exposure ◽  
Ethanol Solution ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Self Administration ◽  
Bdnf Expression ◽  
Sprague Dawley Rats

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.

Modulation of inhibition in the hippocampus in vivo

1985 ◽  
Vol 63 (7) ◽  
pp. 838-842 ◽  
Author(s):  
Nicole Ropert
Keyword(s):  
Membrane Conductance ◽  
Pyramidal Cells ◽  
Medial Septum ◽  
Synaptic Activity ◽  
Sprague Dawley ◽  
In Situ Preparation ◽  
Stratum Pyramidale ◽  
Septal Stimulation ◽  
Sprague Dawley Rats

The nature and mechanisms of septohippocampal transmission have been elucidated by taking advantage of an in situ preparation in experiments with Sprague–Dawley rats under urethane. Both extracellular field potentials and intracellular recordings were made in CA1–3 regions of the hippocampus; and the hippocampal commissure and medial septum stimulated to evoke synaptic activity. Using muscarinic and nicotinic agonists and antagonists it was shown that both acetylcholine and medial septal activity can increase the excitability of pyramidal cells, mainly through muscarinic receptors. The effect of septal stimulation was enhanced by local application of physostigmine and reduced by intraventricular injections of hemicholinium. It was also shown that acetylcholine, when applied in the stratum pyramidale, can reduce the voltage and conductance changes observed during evoked inhibitory postsynaptic potentials (IPSP) without affecting the action of γ-aminobutyric acid on membrane conductance and voltage. It is therefore proposed that acetylcholine can reduce evoked IPSPs through presynaptic inhibition. Evidence is also presented that medial septal stimulation can reduce the efficacy of evoked IPSPs. These observations provide further support for the existence of a cholinergic septohippocampal pathway.

Role of endotoxin in the hypermetabolic state after acute ethanol exposure

1998 ◽  
Vol 275 (6) ◽  
pp. G1252-G1258 ◽  
Author(s):  
Chantal A. Rivera ◽  
Blair U. Bradford ◽  
Vitor Seabra ◽  
Ronald G. Thurman
Keyword(s):  
Oxygen Uptake ◽  
Kupffer Cells ◽  
Ethanol Exposure ◽  
Ethanol Administration ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Hypermetabolic State ◽  
Acute Ethanol ◽  
Eicosanoid Release

This study investigated the role of endotoxin in the hypermetabolic state or swift increase in alcohol metabolism (SIAM) due to acute ethanol exposure. Female Sprague-Dawley rats (100–120 g) were given ethanol (5 g/kg) by gavage. Endotoxin measured in plasma from portal blood was not detectable in saline-treated controls; however, 90 min after ethanol, endotoxin was increased to 85 ± 14 pg/ml, and endotoxin clearance was diminished by ∼50%. Oxygen uptake in perfused livers was increased 48% by ethanol, and production of PGE2 by isolated Kupffer cells was increased similarly. These effects were blunted by elimination of gram-negative bacteria and endotoxin with antibiotics before ethanol administration. To reproduce ethanol-induced endotoxemia, endotoxin was infused via the mesenteric vein at a rate of 2 ng ⋅ kg−1 ⋅ h−1. Endotoxin mimicked the effect of ethanol on oxygen uptake. The specific Kupffer cell toxicant GdCl3completely prevented increases in oxygen uptake due to endotoxin. These findings demonstrate that endotoxin plays a pivotal role in SIAM, most likely by stimulating eicosanoid release from Kupffer cells.

scholarly journals Sex- and Subtype-Specific Adaptations in Excitatory Signaling Onto Deep-Layer Prelimbic Cortical Pyramidal Neurons After Chronic Alcohol Exposure

2021 ◽  
Author(s):  
Benjamin A. Hughes ◽  
Todd K. O’Buckley ◽  
Giorgia Boero ◽  
Melissa A. Herman ◽  
A. Leslie Morrow
Keyword(s):  
Working Memory ◽  
Deep Layer ◽  
Cell Activity ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female ◽  
Gabaergic Neurotransmission ◽  
Male And Female Rats

ABSTRACTLong-term alcohol use results in behavioral deficits including impaired working memory, elevated anxiety, and blunted inhibitory control that are associated with prefrontal cortical (PFC) dysfunction. Preclinical observations demonstrate multiple impairments in GABAergic neurotransmission onto deep-layer principal cells (PCs) in prelimbic cortex that suggest dependence-related cortical dysfunction is the product of elevated excitability in these cells. Despite accumulating evidence showing alcohol-induced changes in interneuron signaling onto PCs differ between sexes, there is limited data explicitly evaluating sex-specific ethanol effects on excitatory signaling onto deep-layer PCs that may further contribute to deficits in PFC-dependent behaviors. To address this, we conducted electrophysiological and behavioral tests in both male and female Sprague-Dawley rats to evaluate the effects of chronic ethanol exposure. Among our observations, we report a marked enhancement in glutamatergic signaling onto deep-layer PCs in male, but not female, rats after alcohol exposure. This phenomenon was furthermore specific to a sub-class of PC, sub-cortically projecting Type-A cells, and coincided with enhanced anxiety-like behavior, but no observable deficit in working memory. In contrast, female rats displayed an alcohol-induced facilitation in working memory performance with no change in expression of anxiety-like behavior. Together, these results suggest fundamental differences in alcohol effects on cell activity, cortical sub-circuits, and PFC-dependent behaviors across male and female rats.

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