Interleukin-1ß and TNF-α are elevated in the amygdala of adult rats prenatally exposed to ethanol.

Affective disorders, including anxiety and depression, developed in adult offspring of the mothers who consumed alcohol during pregnancy could be associated with an imbalance in neuroimmune factors in the amygdala (corpus amygdaloideum) resulted in impaired emotional stimulus processing. The aim of this study was to compare the content of cytokines TNF-α, IL-1α, IL-1ß, IL-10, and IL-17 in the amygdala of adult female rats exposed to alcohol in utero and control rats. Cytokine levels were evaluated using a multiplex immunoassay system; mRNA expression was investigated using a real-time reverse transcription-polymerase chain reaction (RT-qPCR) assay. Prenatal alcohol exposure led to the increase in the content of TNF-α and IL-1ß without significant changes in the mRNA expression level. Our data suggest that ethanol exposure to the fetus during pregnancy can result in long-term alterations in the content of the key neuroinflammatory factors in the amygdala, which in turn can be a risk factor for affective disorders in the adulthood.

[Experimental approaches to the investigation of behavioral disorders associated with prenatal alcohol exposure]. / Éksperimental'nye podkhody k izucheniiu povedencheskikh narushenii, assotsiirovannykh s prenatal'nym deistviem alkogolia.

Fetal alcohol spectrum disorders (FASD) is an umbrella term which covers a wide range of deficits in prenatal and postnatal growth, anatomy and CNS functions produced by prenatal alcohol exposure. The most severe form of FASD is fetal alcohol syndrome (FAS) characterized by additional specific craniofacial and brain malformations. Despite a high prevalence and extensive clinical studies, the fundamental mechanisms of FASD are still poorly understood. Thereby, experimental models, which allow better control for both socio-environmental and genetic factors, are critical to our understanding of FASD. The review is focused on the effects of exposure to alcohol during the prenatal period in animal models. The authors outline that prenatally alcohol-induced changes in motor and executive functions, learning and memory, stress reactivity and affective state are remarkably parallel between animals and humans. Finally, the authors consider a potential impact of postnatal social and environmental factors on the outcome in experimental models of FASD.

[An effect of cabergoline on alcohol consumption and DRD2 expression in the brain of rats with chronic alcohol intoxication]. / Vliyanie kabergolina na potreblenie alkogolya i ekspressiyu gena DRD2 v mozge krys s khronicheskoi alkogol'noi intoksikatsiei.

AIM: Cabergoline is a high selective agonist of dopamine D2 receptors (D2R). The activation of D2R plays an important role in the regulation of dopamine transmission, the imbalance of which is thought to underlie the development of alcohol motivation. To examine this possibility, cabergoline effects on alcohol consumption and brain DRD2 expression in rats with chronic alcohol intoxication were studied. MATERIAL AND METHODS: Male Wister rats were studied using the following methods: modelling of chronic alcohol intoxication, testing in «10% alcohol vs water¼ choice regimen, quantitative RT-PCR. RESULTS: Systemic administration of 0.5 mg/kg of cabergoline significantly decreases alcohol intake in alcohol-preferring rats. At the same time, cabergoline elevates the DRD2 expression in the midbrain and striatum of high-alcohol-preferring rats but not in intact (alcohol-naïve) animals. CONCLUSION: The involvement of cabergoline in the DRD2 expression may lead to the decrease in alcohol motivation. These findings indicate that cabergoline needs further investigations as a new potential medication for alcohol use disorder.

Modulation of peripheral opioid receptors affects the concentration of mu-opioid receptors in rat brain.

Radioligand binding assay was used to evaluate characteristics of central mu-opioid receptors after peripheral administration of mu-opioid receptor agonist loperamide and antagonist methylnaloxone. These substances do not cross the blood-brain barrier. Loperamide and methylnaloxone produced opposite effects on the density of mu-opioid receptors in the frontal cortex of rat brain. These data confirm our hypothesis on reciprocal interactions between central and peripheral compartments of the endogenous opioid system.

Effect of nooglutil on benzodiazepine withdrawal syndrome and binding of 3H-spiperone with D2 receptors in rat striatum.

A new nootropic preparation nooglutil (N-(5-oxynicotinoyl)-L-glutamic acid), a positive modulator of AMPA receptors for glutamate, administered intraperitoneally in a dose of 70 mg/kg reduced anxiety of rats in the Vogel conflict test after 24-h withdrawal from chronic diazepam treatment (4 mg/kg intraperitoneally for 45 days). Nooglutil (5 nM-750 microM) had no effect on in vitro binding of (3)H-spiperone in intact rats. Systemic administration of 50 mg/kg nooglutil in vivo increased the dissociation constant and density of D(2)receptors. Increasing the dose to 100 mg/kg abolished this effect. Our findings suggest that nooglutil produces an indirect effect on the brain dopaminergic system under normal and pathological conditions and this effect is probably mediated via the glutamatergic system.