The review summarizes current literature data on the structure of heteromeric complexes of dopamine receptors and their possible role in physiological and pathological processes in the brain. It includes analysis of studies on dopamine D1–D2 receptor complexes, their localization in the brain and the functional role. Functionally, these receptor complexes employ a principally different pathway of signal transduction as compared to the parent homomeric receptors. Investigation of dopamine receptor heteromers extends our understanding of the mechanisms of ligand-receptor interaction and opens new opportunities for the development of pharmacological agents for the treatment of psychiatric disorders associated with impaired dopaminergic neurotransmission, particularly, drug dependence.

Maternal alcohol consumption is one of the strong predictive factors of alcohol use and consequent abuse; however, investigations of sex differences in response to prenatal alcohol exposure (PAE) are limited. Here we compared the effects of PAE throughout gestation on alcohol preference, state anxiety and mRNA expression of presynaptic proteins α-, β- and γ-synucleins in the brain of adult (PND60) male and female Wistar rats. Total RNA was isolated from the hippocampus, midbrain and hypothalamus and mRNA levels were assessed with quantitative RT-PCR. Compared with naïve males, naïve female rats consumed more alcohol in “free choice” paradigm (10% ethanol vs. water). At the same time, PAE produced significant increase in alcohol consumption and preference in males but not in females compared to male and female naïve groups, correspondingly. We found significantly lower α-synuclein mRNA levels in the hippocampus and midbrain of females compared to males and significant decrease in α-synuclein mRNA in these brain areas in PAE males, but not in females compared to the same sex controls. These findings indicate that the impact of PAE on transcriptional regulation of synucleins may be sex-dependent, and in males’ disruption in α-synuclein mRNA expression may contribute to increased vulnerability to alcohol-associated behavior.

Neurokinin‐1 receptor (NK1r) antagonists have been shown to suppress operant self‐administration of alcohol, voluntary alcohol consumption and stress‐induced reinstatement of alcohol‐seeking behaviour. Considering the long half‐life and anxiolytic‐like properties of NK1r antagonist rolapitant, we expected that it may be an effective option for reducing anxiety and alcohol motivation during early withdrawal. Voluntary alcohol intake (two‐bottles paradigm) was recorded in male Wistar rats during the three periods: 24 days (basal level), 6‐day period when rats received 5 mg·kg⁻¹ rolapitant or vehicle and 12‐h period after repeated withdrawal episodes (alcohol cessation for 36 h). We found that upon intraperitoneal (i.p.) administration, rolapitant rapidly penetrated into specific rat brain regions – amygdala, hypothalamus and neocortex – implicated in the control of anxiety and reward. Rolapitant did not affect basal voluntary alcohol intake, but significantly suppressed anxiety‐like behaviour and alcohol consumption following withdrawal episodes. Our findings suggest that rolapitant should be further investigated as a novel treatment option for relapse prevention in alcohol‐dependent patients.

Neuroinflammation can be an important factor of many disorders in central nervous system (CNS) including cognitive dysfunction, affective disorders, and addictive behavior associated with prenatal alcohol exposure and presented in early adulthood. In this study we used an experimental rodent model of prenatal alcohol (PA) exposure (consumption of a 10% ethanol solution by female Wistar rats throughout pregnancy), multiplex immunofluorescence analysis of interleukins (IL-1α, IL-1β, IL-3, IL-6, IL-9, and IL-12), tumor necrosis factor (TNF-α), and chemokine CCL5, as well as quantitative real-time PCR to assess the level of cytokine mRNAs in the prefrontal cortex of the sexually mature (PND60) offspring – male and female rats with prenatal alcohol intoxication and control animals. Significant decrease in the content of TNF-α and interleukins IL-1β, IL-3, IL-6, IL-9 was detected in the prefrontal cortex of male, but not in the female PA offspring. Importantly, PA males also showed decrease in the level of TNF-α mRNA in the prefrontal cortex by 45% compared to the control males, which may underlie the detected decrease in its content. Taken together, our study demonstrates that a number of neuroimmune factors are regulated in a sex-specific manner in the prefrontal cortex and are differentially affected in males and females by the prenatal exposure to alcohol. Sex factor must be taken into account when conducting further translational studies of the fetal alcohol spectrum disorders and developing new methods for prevention and therapy.