Metabotropic glutamate receptors (mGluRs) are expressed predominantly on neurons and glial cells and are involved in the modulation of a wide range of signal transduction cascades. Therefore, different subtypes of mGluRs are considered a promising target for the treatment of various brain diseases. Previous studies have demonstrated the seizure-induced upregulation of mGluR5; however, its functional significance is still unclear. In the present study, we aimed to clarify the effect of treatment with the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that the administration of MTEP during the latent phase of the model did not improve survival, prevent the development of epilepsy, or attenuate its manifestations in rats. However, MTEP treatment completely prevented neuronal loss and partially attenuated astrogliosis in the hippocampus. An increase in excitatory amino acid transporter 2 expression, which has been detected in treated rats, may prevent excitotoxicity and be a potential mechanism of neuroprotection. We also found that MTEP administration did not prevent the behavioral comorbidities such as depressive-like behavior, motor hyperactivity, reduction of exploratory behavior, and cognitive impairments typical in the lithium–pilocarpine model. Thus, despite the distinct neuroprotective effect, the MTEP treatment was ineffective in preventing epilepsy.

DAT-HET rats with their underlying hyperdopaminergia are a promising model for the investigation of neuropsychiatric diseases, which are based on impaired dopamine neurotransmission, including alcoholism. The aim of the work was to evaluate the effect of free alcoholization on drinking, locomotor, exploratory behavior, anxiety, and Tyrosine hydroxylase (TH) levels in rats with impaired functioning of the DA system (DAT-HET). The study was carried out on adult male rats of the DAT-HET (n = 15) and Wistar (n = 13), which were divided into 4 groups: “DAT-HET ethanol” (n = 10) and “Wistar ethanol” (n = 9), who were in the mode of free alcoholization for 112 days of the experiment. The DAT-HET water (n = 5) and Wistar water (n = 4) groups did not have access to an ethanol solution and did not participate in behavioral tests. Ethanol preference and consumption was assessed in the “Two-bottle choice test”. The amount of ethanol consumed in the cells was recorded weekly. Behavior was assessed using the Open Field and Elevated Plus Maze tests. After alcoholization, to assess the level of TH, an immunohistochemical (IHC). It was found that during free alcoholization, DAT-HET rats do not form preferences for ethanol. Under the low ethanol consumption, the initial hyperactivity in DAT-HET rats is leveled. The DAT-HET model leads to an increase in TH levels in nAcc. In addition, the free alcoholization reduces the level of TH in nAcc with the development of a pathological increase in TH, observed in the DAT-HET model, but has no effect on healthy animals.

Background/Objectives: Chronic ethanol consumption damages erythrocyte membranes, reducing their deformability and disrupting erythropoiesis. Dopaminergic signalling plays an important role in regulating haematopoietic stem cells. However, the impact of genetic alterations in the dopamine system on the functional properties of erythrocytes and their resistance to the toxic effects of alcohol remains understudied. In this study, we evaluated haematological parameters and the sensitivity of erythrocytes to chronic ethanol exposure in DAT-HET rats (heterozygous for the dopamine transporter gene) compared to Wistar rats. Methods: Both lines of rats were subjected to chronic alcoholisation (10% ethanol for six months). Flow cytometry was used to assess reticulocyte production, intracellular esterase activity (cell viability), and membrane lipid asymmetry disruptions. Laser diffraction was used to evaluate osmotic resistance (deformability). Results: The partial knockout of the DAT gene significantly altered the baseline haematological profile, resulting in pronounced leukopenia, moderate thrombocytopenia, moderate erythrocyte macrocytosis, and reduced intracellular esterase activity. The consequences of chronic ethanol consumption in Wistar rats (anaemia, decreased reticulocyte count, increased osmotic rigidity of erythrocytes, and an increased proportion of annexin-positive cells) were similar to those observed in humans, thus confirming the validity of the experimental model. In contrast, chronic alcohol exposure did not significantly influence haematopoiesis parameters or erythrocyte biophysical properties in DAT-HET rats, indicating that even a 50% loss of the dopamine transporter strongly prevented ethanol’s damaging effects on blood cells. Conclusions: The marked contrast between Wistar rats (which develop alcohol-induced anaemia and erythrocyte dysfunction similar to humans) and DAT-HET rats (which remain largely unaffected) demonstrates that dopaminergic signalling plays a previously unrecognised role in determining erythrocyte sensitivity to alcohol toxicity.

DAT-HET rats with their underlying hyperdopaminergia are a promising model for the investigation of neuropsychiatric diseases, which are based on impaired dopamine neurotransmission, including alcoholism. The aim of the work was to evaluate the effect of free alcoholization on drinking, locomotor, exploratory behavior, anxiety, and Tyrosine hydroxylase (TH) levels in rats with impaired functioning of the DA system (DAT-HET). The study was carried out on adult male rats of the DAT-HET (n = 15) and Wistar (n = 13), which were divided into 4 groups: “DAT-HET ethanol” (n = 10) and “Wistar ethanol” (n = 9), who were in the mode of free alcoholization for 112 days of the experiment. The DAT-HET water (n = 5) and Wistar water (n = 4) groups did not have access to an ethanol solution and did not participate in behavioral tests. Ethanol preference and consumption was assessed in the “Two-bottle test”. The amount of ethanol consumed in the cells was recorded weekly. Behavior was assessed using the Open Field and Elevated Plus Maze tests. After alcoholization, to assess the level of TH, an immunohistochemical (IHC). It was found that during free alcoholization, DAT-HET rats do not form preferences for ethanol. Under the low ethanol consumption, the initial hyperactivity in DAT-HET rats is leveled. The DAT-HET model leads to an increase in TH levels in NAcc. In addition, the free alcoholization reduces the level of TG in NAcc with the development of a pathological increase in TH, observed in the DAT-HET model, but has no effect on healthy animals.