The aim of the work was to study the limbic-neocortical and monoaminergic features of the development of withdrawal syndrome of volatile organic compounds (VOC) inhalations in rats. The study was carried out in 30 three months old male rats with dependence on inhalations of organic solvent “646” which contains up to 50 % mix of toluene and acetone. It has been shown that the withdrawal syndrome of inhalant is characterized by increased excitability and behavioral manifestations of equivalents of convulsive reactions such as oral hyperkinesis, head shaking and changes in the frequencyamplitude spectrum of the biopotentials in structures of the brain limbic-neocortical system with the initiation in the medial olfactory region and hippocampus. At the hypothalamus level, withdrawal of VOC inhalations produces the depleting impact on the catecholaminergic structures with a stronger effect in neuronal endings with adrenaline as neurotransmitter. Withdrawal syndrome evokes a significant decrease in dopamine content by 61 %, noradrenaline by 77 % and adrenaline by 92 % in the hypothalamus and increase in serotonin concentration in blood serum by 16 % in rats with initial preference to inhalations of organic solvent “646”. In rats with the absence of initial preference to inhalations of organic solvent “646” a decrease in adrenaline level in the hypothalamus by 77 % was detected.