Stress related (acute stress reaction, posttraumatic stress disorder) and eating disorders, addictions (alcoholism), aggressive/suicidal behavior, and attention deficit hyperactivity disorder are frequent multifactorial and polygenic psychiatric disorders that induce a great suffering in patients and their families, and carry financial burden to the whole society. Molecular basis of these disorders involves the changes in neurotransmitter (primarily serotonin - 5-HT, noradrenalin, dopamine) and neuroendocrine systems, and functional gene polymorphisms controlling the activity of the corresponding proteins.
Serotonergic and catecholaminergic (dopaminergic, noradrenergic) neurotransmitter systems regulate physiological functions and are also connected to the etiology of complex and polygenic neuropsychiatric disorders (Alzheimer’s disease /AD/, frontotemporal dementia, schizophrenia and depression). Etiology and psychobiological mechanisms of neuropsychiatric disorders is not well understood, but could be the result of interaction of genetic factors, specific proteins and environment.
The purpose of the present research is to improve our understanding of the mechanisms of action of neuropshycoactive drugs, especially during their chronic administration and modification by stress. Particular emphasis is placed on the research of benzodiazepines and antidepressants, used to treat anxiety, insomnia and depression, which are acting via GABAergic and serotonergic systems in the brain. Therefore, we investigate the changes in the expression and function of GABA-A receptor in vitro after prolonged exposure to benzodiazepines, known to induce the development of tolerance and dependence. Moreover, by using experimental animals, we have been also investigating the interactions between the effects of stress and benzodiazepines and antidepressants, primarily on the susceptibility to convulsions, as well as the role of the serotonergic system in controlling brain excitability.