An Intricated Pas de Deux of Addicted Brain and Body Is Orchestrated by Stress and Neuroplasticity

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Abstract

Dependence on psychoactive substances is a phenomenon that is based on the alterations of common molecular cellular mechanisms, structures and neuronal networks underlying normal brain functioning and realizing stress response, reinforcement and aversion, learning and memory. As a result, aberrant neuroplasticity states associated with somatic changes are formed, which determine the pathogenesis and symptoms of chemical dependence and at the same time can be considered as targets for the development of therapies for such addictions. An integrative scheme of stress and neuroplastic changes participation in the formation of the vicious circle of pathological substance dependence syndrome based on a holistic approach is presented.

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About the authors

N. V. Gulyaeva

Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences; Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department

Author for correspondence.
Email: nata_gul@ihna.ru
Russian Federation, 117485, Moscow; 115419, Moscow

D. I. Peregud

Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences; Serbsky National Medical Research Center for Psychiatry and Drug Addiction

Email: nata_gul@ihna.ru
Russian Federation, 117485, Moscow; 119034, Moscow

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2. Fig. 1. The involvement of stress and neuroplastic changes in the formation of the vicious circle of the syndrome of pathological dependence on psychoactive substances (surfactants): a holistic approach. The development of addiction to surfactants is based on the fundamental mechanisms of normal brain functioning, including stress reactivity, reinforcement (positive and negative), learning and memory. Various surfactants, along with specific effects, cause typical adaptive and pathological processes at the molecular, cellular and functional levels. In the process of addiction formation, the key mechanism of the surfactant effect on the normally functioning positive reinforcement system is the stimulation of dopaminergic projections of the ventral region of the tire into the striatum (STR) and the effect on the prefrontal cortex (PFC). At the same time, stress factors, the action of which is mediated by the stress-reactive hypothalamic-pituitary-adrenal axis (HGNO; GP – hypothalamus, GF – pituitary gland, NP – adrenal glands) in interaction with the nuclei of the amygdala (AM) contribute to voluntary chronic intoxication, which becomes uncontrollable. This is accompanied by the development of tolerance to surfactants and the formation of conditional associative connections, while a system of key structures in the processes of learning and memory is activated: the hippocampus (GP), PFC and AM, which has close links with HGNO. The cessation of surfactant intake in the case of formed dependence is accompanied by the development of withdrawal syndrome (withdrawal syndrome), which, manifesting itself on the physiological and affective levels, is associated with a decrease in positive reinforcement. Withdrawal disorders are becoming a new severe stress factor, on the basis of which negative reinforcement is formed, mediated by HGNO and AM. The manifestation of relapse, which develops against the background of a weakening of control by the PFC, is also associated with HGNO dysfunction. Reconsolidation of memory is a physiological trigger of relapse, and AM, GP, and STR are key structures. Changes in neuroplasticity associated with the development of addiction cover all levels, from epigenetic, molecular and synaptic to cellular and network. Chronic intoxication of surfactants leads to both adaptive and pathological changes in the expression of various genes, neurochemical disorders in the systems of neurotransmitters and trophic factors, the development of the inflammatory process and, as a result, structural and functional rearrangements of the involved structures. It should be noted that the associations of brain structures with certain stages of addiction formation shown in the figure are rather arbitrary and cannot take into account all known connections between these and other brain structures. Nevertheless, it is obvious that the functional pleiotropy of brain structures involved in stress, adaptation, learning and memory processes, characteristic of a healthy brain, plays an important role in the formation of addiction, on the one hand, providing adaptation processes to surfactant intoxication, and on the other hand, forming a pathological phenotype of addiction. As a result, dependence on surfactants is realized on the basis of fundamental physiological mechanisms of brain functioning, such as stress, reinforcement and aversion, learning and memory. The integrated circuit shown in this figure uses the information provided in the articles. [12, 13, 18, 25-28], as well as the Servier Medical Art (Servier) templates provided under the free Creative Commons Attribution 3.0 unported license

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