Author details

GABA and impairment to synaptic transmission. Our results are consistent with other studies that showed a reduction in the function of GABAA/BzDR in the prefrontal cortex in patients with alcohol dependence [36, 55]. Alcohol causes neuroplastic changes in BzDR associated with a decrease in the affinity of the receptors, a change in the conformational state of the GABAA/BzD rector complex, as a result of inhibition of the binding kinetics of BzDR by the polypeptide DBI (Diazepam Binding Inhibitor), as well as its metabolites. The endogenous peptide DBI possesses anxiogenic action and is the inverse agonist of BzDR [62]. Chronic alcohol exposure induces the expression of endogenous DBI interacting with receptors and suppresses binding affinity to [3

Neuroplastic changes of GABAAR, caused by the influence of ethanol, are associated with a change in the composition of subunits of the receptor complex and change in the pharmacological sensitivity and receptor function associated with the development of tolerance to ethanol and alcohol dependence. High heterogeneity of different isoforms of subunits of the GABAA receptor (α1-α6; β2,β3) in various regions of the brain: nuclei of the basal ganglia, prefrontal cortex and limbic regions of the brain, underlies the functional differentiation of the GABAA receptor complex and provides a varying degree of modulation functions of GABAAR by ethanol in various brain structures [63]. Changes in the expression of neuronal elements induced by alcohol, leading to changes in neurotransmitter function adaptation systems in the

Benzodiazepines, anxiolytics, anesthetics and alcohol are implementing some of its effects through the BzDR "central" and "peripheral" types regulating the synthesis of neurosteroids, which are critical for the provision of brain functions. Ethanol modulates GABAA/BzD receptor complex function by affecting synthesis neurosteroids de novo in the brain, stimulating the mitochondrial receptors of the "peripheral type"—PBR, providing the transfer of cholesterol to mitochondria and synthesizing neurosteroids, independent of the functions of the HPA axis. This mechanism can play a principal role in the central effects of alcohol. Thus, the functional activity of PBR has a modulating effect on GABAergic function in the structures of the brain,

Alcohol does not have specific receptors in the brain; however, the receptor proteins are exposed to ethanol. The research of a number of authors is aimed at studying long-lasting adaptive changes (neuroplasticity), which contribute to the development of alcohol dependence. Our studies aimed at studying neuroadaptation under the influence of chronic alcohol effects on the benzodiazepine receptor system of the brain have revealed that a low affinity of BzDR can be a marker of disorders of synaptogenesis and regulatory mechanisms mediating the GABAA/BzDR

BzDR "central" and "peripheral" types can be a key link to the discovery of new promising therapy for the treatment of compulsive craving for alcohol, alcohol abuse and dependence. The integration of current data and our data is necessary to define the role of GABAAR in modulating the rewarding and aversive effects of ethanol and may lead to the development of pharmacotherapy that targets GABAA/BzD receptors to treat alcoholism in human beings

bond that induces receptor neuroplasticity and alcohol addiction [41, 54, 65, 66].

flunitrazepam.

96 Drug Addiction

[65–68].

brain associated with neuroplasticity [64].

reacting to various neurotoxic effects and damage [65].

Tamara V. Shushpanova1 \*, Anatoly Solonskii<sup>1</sup> and Olga V. Shushpanova2

\*Address all correspondence to: shush59@mail.ru

1 Department of Clinical Psychoneuroimmunology and Neurobiology, Mental Health Research Institute, Tomsk National Research Medical Center Russian Academy of Science, Tomsk, Russia

2 Department of Child Psychiatry, Scientific Center of Mental Health, Moscow, Russia
