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.

[The role of nociceptin in opioid regulation of brain functions]. / Rol' notsitseptina v mekhanizmakh opioidnoi reguliatsii funktsii mozga.

This review discusses our current knowledge on the nociceptin/orphanin (N/OFQ) system regarding its role in regulation of brain functions. Nociceptin receptor (NOPr) was identified in 1994 [Bunzow et al., 1994; Mollereau et al., 1994]. In 1995 a 17 amino acid endogenous peptide was found to be the high-affinity ligand for the NOPr [Reinscheid et al., 1995]. N/OFQ has a broad spectrum of activity and can act as on opioid-like as well as an anti-opioid peptide. Considering high level of N/OFQ and NOPr mRNA expression in the limbic brain regions, the N/OFQ/NOP system is suggested to be involved in regulation of emotions, resward, pain sensitivity, stress responsibility, sexual behavior, aggression, drug abuse and addiction. However it is still not well understood whether an increased vulnerability to drugs of abuse may be associated with dysregulation of N/OFQ/NOP system. Current review further highlights a need for further research on N/OFQ/NOP system as it could have clinical utility for substance abuse, depression, and anxiety pharmacotherapy.

[The effect of the dopamine D2 receptor agonist cabergoline on the content of catecholamines and expression of BDNF mRNA in the rat midbrain and hypothalamus]. / Vliianie agonista dofaminovykh D2-retseptorov kabergolina na soderzhanie katekholaminov i ékspressiiu mRNK BDNF v srednem mozge i gipotalamuse v éksperimente.

AIM: To study an effect of cabergoline on dopamine and noradrenaline concentration and BDNF mRNA level in the rat midbrain and hypothalamus. MATERIAL AND METHODS: Twenty adult male Wistar rats were used in a single treatment paradigm: animals of the treatment group (n=10) received cabergoline (i.p., 0.5 mg/kg) and the control group (n=10) received an equivalent volume of the solvent. Quantitative analysis for the dopamine (DA) and noradrenaline (NA) was carried out using high-performance liquid chromatography (HPLC) coupled with electrochemical detection. BDNF mRNA levels were studied using quantitative RT-PCR. RESULTS AND CONCLUSION: Cabergoline significantly increases NA concentration in the midbrain 24 hours after injection: 639.2±64.5 ng/g in the treatment group versus 398.0±66.0 ng/g in the control group (p<0.05), while mean content of DA is not significantly changed (211.4±16.3 ng/g vs 169.7±54.6 ng/g, respectively). Cabergoline does not affect hypothalamic DA and NA levels. The drug increases BDNF mRNA levels by 2-times in the midbrain, but not in the hypothalamus, 24 hours after injection.

[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.

[Heterodimeric D1-D2 dopamine receptors: a review]. / Geteromernye kompleksy D1-D2-dofaminovykh retseptorov: obzor literaturnykh dannykh.

This review summarizes modern data on the structure and functions ofheteromersformed by D1 and D2 dopamine receptors focusing on their role in the mechanisms of drug dependence. This article discusses potential functional significance of heterodimeric D1-D2 dopamine receptorsdue to their localization in the brain as well as unique pharmacological propertiesversus constituent monomers. It is shown that heteromerization results in dramatic changes in activated signaling pathways compare to the corresponding monomers. These studies update our current knowledge of ligand-receptor interactions and provide better understanding of dopamine receptors pharmacology. Furthermore elucidation of significance of heterodimeric D1-D2 dopamine receptors as drug targets is important for the development of new effective drug addiction treatment.

[A profile of antidepressive effects of agomelatine and a current view on the mechanism of its action]. / Profil' antidepressivnykh éffektov agomelatina i sovremennyi vzgliad na mekhanizm ego deistviia.

Agomelatine is one of the latest antidepressants (melatoninergic agonists) with a new mechanism of action. From the positions of classical monoaminoergic theory, tts mechanism of action is difficult to understand, because the drug increases the levels of monoamines and neurotrophic factors, while not affecting their reuptake and negative feedback, which control neurotransmission level. Besides the effect on suprachiasmatic nucleus, a relevant role in the mechanism of action of agomelatine plays its special functionally selective (with regard to intracellular signaling pathways) interaction with heteromeric complexes of serotonin 5-НТ2С and melatonin MT2 receptors in the hippocampus and cerebral cortex. Agomelatine is competitive to other modern antidepressants in the efficacy assessed by the percentage of complete responders and superior in the total frequency of remissions. Compared to other SSRI antidepressants, agomelatine is more effective for anhedonia. In these cases, agomelatine increases the level of brain-derived neurotrophic factor (BDNF) in the blood of responders.

[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.