Acute effects of alcohol on brain perfusion monitored with arterial spin labeling magnetic resonance imaging in young adults

While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6 g/kg followed by a steady exposure of 100 minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tolerance effect is not observable on the time scale of 2 hours. Larger studies are needed to investigate the origin and the consequences of the effect, as well as the correlates of inter-subject variations.     

Mifepristone in the Central Nucleus of the Amygdala Reduces Yohimbine Stress-Induced Reinstatement of Ethanol-Seeking

Chronic ethanol exposure leads to dysregulation of the hypothalamic-pituitary-adrenal axis, leading to changes in glucocorticoid release and function that have been proposed to maintain pathological alcohol consumption and increase vulnerability to relapse during abstinence. The objective of this study was to determine whether mifepristone, a glucocorticoid receptor antagonist, plays a role in ethanol self-administration and reinstatement. Male, Long–Evans rats were trained to self-administer either ethanol or sucrose in daily 30 min operant self-administration sessions using a fixed ratio 3 schedule of reinforcement. Following establishment of stable baseline responding, we examined the effects of mifepristone on maintained responding and yohimbine-induced increases in responding for ethanol and sucrose. Lever responding was extinguished in separate groups of rats and animals were tested for yohimbine-induced reinstatement and corticosterone release. We also investigated the effects of local mifepristone infusions into the central amygdala (CeA) on yohimbine-induced reinstatement of ethanol- and sucrose-seeking. In addition, we infused mifepristone into the basolateral amygdala (BLA) in ethanol-seeking animals as an anatomical control. We show that both systemic and intra-CeA (but not BLA) mifepristone administration suppressed yohimbine-induced reinstatement of ethanol-seeking, while only systemic injections attenuated sucrose-seeking. In contrast, baseline consumption, yohimbine-induced increases in responding, and circulating CORT levels were unaffected. The data indicate that the CeA plays an important role in the effects of mifepristone on yohimbine-induced reinstatement of ethanol-seeking. Mifepristone may be a valuable pharmacotherapeutic strategy for preventing relapse to alcohol use disorders and, as it is FDA approved, may be a candidate for clinical trials in the near future.     

Preventive Effect of the Flavonoid, Wogonin, Against Ethanol-Induced Gastric Mucosal Damage in Rats

Whether wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of Scutellaria baicalensis Georgi, which has been shown to have antiinflammatory and antitumor activities in various cell types, possesses a gastric cytoprotective effect was investigated in an ethanol-induced gastric damage model in rats. Ethanol administration alone induced evident gastric damage including gastric hemorrhages and edema, while this gastric damage was significantly attenuated by wogonin pretreatment (30 mg/kg B.W.) 1 hr before ethanol administration. As major protective mechanisms of wogonin on ethanol-induced gastric damage, we found that wogonin showed either antiinflammatory effects through dual actions on arachidonic acid metabolism, i.e., induction of prostaglandin D2 and suppression of 5S-hydroxyeicosatetraenoic acid (5S-HETE), or preventive induction of profuse apoptosis in the stomach. Conclusively, the flavonoid wogonin could be used as a preventive agent of alcohol-induced gastropathy, whose actions were proven to be strong antiinflammation and apoptosis induction.     

Cardiac electrophysiological actions and interactions of ethanol, cocaine, and the metabolite ethylcocaine

The influence of ethanol on the actions of cocaine and ethylcocaine on rat sinoatrial preparations was studied. Ethanol did not modify the depressant effect of cocaine or ethylcocaine on sinoatrial rate (SR) in preparations with spontaneous activity. Cocaine produced sinoatrial block only in the presence of ethanol, and the latter accentuated the sinoatrial block produced by ethylcocaine. Ethanol did not modify the depressant effect of cocaine or ethylcocaine on membrane potentials of atrial fibers in preparations driven at a constant rate. In conclusion, ethanol, in a concentration that did not by itself affect SR or produce sinoatrial block, accentuated the effects of cocaine and ethylcocaine on sinoatrial conduction, without modifying the effects on SR. It is proposed that the accentuation of the block was the consequence of the combination of a depressant action on the fast sodium system and a deterioration of the cell-to-cell coupling.     

芡实醇提物对糖尿病肾病大鼠肾功能的影响及其体外抗氧化能力测定

目的 探讨芡实醇提物对糖尿病肾病大鼠肾功能的影响,并测定芡实醇提物、水提物上清和沉淀的体外抗氧化能力。方法 80%乙醇提取芡实种仁,浓缩冻干后得干燥粉末,药渣采用水提醇沉法,经抽滤旋蒸制备上清和沉淀。雄性SD大鼠腹腔注射链脲佐菌素60 mg/kg诱导糖尿病肾病模型,灌胃给予芡实醇提物(75、150、300、600 mg/kg)12周后,检测大鼠尿蛋白、尿微量白蛋白、血肌酐(Cr)和尿素氮(BUN)含量,并观察肾组织病理学变化。通过对Fe3+还原力、1,1-二硝基-2-三硝基苯肼(DPPH)、O2-和OH-自由基清除率的比较,测定3种提取物的抗氧化能力。结果 与糖尿病肾病模型组比较,各剂量芡实给药组均能降低大鼠24 h尿蛋白和尿微量白蛋白含量,芡实150和600 mg/kg组尿蛋白显著降低(P<0.05);与模型组比较,各剂量芡实给药组大鼠血中BUN均有不同程度降低,芡实300 mg/kg组降低更为显著(P<0.01)。12周末肾组织病理学观察结果表明,芡实醇提物300和600 mg/kg能够明显减轻肾组织损伤。芡实醇提物在浓度为0.6、0.8和1.0 mg/ml时,显示有一定的抗氧化能力,表现为对Fe3+的还原,对DPPH、O2-和OH-的清除。结论 芡实醇提物具有降低糖尿病肾病大鼠尿蛋白的作用,该作用可能与其抗氧化能力有关。     

Adolescent Intermittent Ethanol Exposure Is Associated with Increased Risky Choice and Decreased Dopaminergic and Cholinergic Neuron Markers in Adult Rats

Background:

Binge drinking is prevalent during adolescence and may have effects on the adult brain and behavior. The present study investigated whether adolescent intermittent ethanol exposure alters adult risky choice and prefrontal dopaminergic and forebrain cholinergic neuronal marker levels in male Wistar rats.

Methods:

Adolescent (postnatal day 28–53) rats were administered 5g/kg of 25% (vol/vol) ethanol 3 times/d in a 2-days–on/2-days–off exposure pattern. In adulthood, risky choice was assessed in the probability discounting task with descending and ascending series of large reward probabilities and after acute ethanol challenge. Immunohistochemical analyses assessed tyrosine hydroxylase, a marker of dopamine and norepinephrine in the prelimbic and infralimbic cortices, and choline acetyltransferase, a marker of cholinergic neurons, in the basal forebrain.

Results:

All of the rats preferred the large reward when it was delivered with high probability. When the large reward became unlikely, control rats preferred the smaller, safe reward, whereas adolescent intermittent ethanol-exposed rats continued to prefer the risky alternative. Acute ethanol had no effect on risky choice in either group of rats. Tyrosine hydroxylase (prelimbic cortex only) and choline acetyltransferase immunoreactivity levels were decreased in adolescent intermittent ethanol-exposed rats compared with controls. Risky choice was negatively correlated with choline acetyltransferase, implicating decreased forebrain cholinergic activity in risky choice.

Conclusions:

The decreases in tyrosine hydroxylase and choline acetyltransferase immunoreactivity suggest that adolescent intermittent ethanol exposure has enduring neural effects that may lead to altered adult behaviors, such as increased risky decision making. In humans, increased risky decision making could lead to maladaptive, potentially harmful consequences.