GLUTAMATERGIC DYSREGULATION UNDER COMBINED EXPOSURE TO ETHANOL AND MORPHINE

Background. Glutamate plays a key role in excitatory neurotransmission and neuroplasticity, as well as in addiction. While the isolated effects of ethanol and morphine on its levels in the brain are well known, the combined effects of these psychoactive substances on glutamate concentrations in the central nervous system have been poorly studied. Objective. To evaluate changes in the functional relationships of glutamate with neuroactive transmitters in various brain structures of rats following a single combined administration of ethanol and morphine. Material and methods. Albino male rats (n=43) divided into five groups were used in the experiment. A single intragastric administration of ethanol and intraperitoneal administration of morphine were performed, as well as their combined administration in varying orders at 12-hour intervals. Neurotransmitter and neurotransmitter amino acid concentrations were determined in the cerebral hemispheres, striatum, hypothalamus, midbrain, and cerebellum by ion-pair high-performance liquid chromatography with fluorescence detection. The relationships between glutamate levels and other neuroactive substances were assessed using Spearman correlation analysis. Results. In acute alcohol intoxication, a statistically significant positive correlation was found between glutamate and the inhibitory neurotransmitter amino acids gamma-aminobutyric acid (GABA) and glycine, despite a significant decrease in glutamate levels in the cerebral hemispheres. Of particular interest were the experimental groups with combined psychoactive substance administration: morphine followed by ethanol resulted in increased glutamate levels in the hypothalamus and a strong glutamate/aspartate correlation, as well as a glutamate/dopamine correlation in the striatum and cerebral hemispheres. In the ethanol+morphine group, glutamate concentrations remained stable, but there was a positive correlation with aspartate in the cerebellum and striatum, with GABA and aspartate in the hypothalamus, as well as with glycine and aspartate in the cerebral hemispheres, while a strong negative correlation with norepinephrine was observed in the striatum. Conclusion. Despite relatively stable glutamate levels in the brain following a single combined administration of ethanol and morphine, significant changes in its correlations with other studied neurotransmitters were detected in various areas of the central nervous system. This may indicate functional dysregulation of the glutamatergic neurotransmitter system, as well as an imbalance between excitatory and inhibitory amino acids in the brain following combined administration of ethanol and morphine.