HOLUBOVA, Kristina, Tereza NEKOVAROVA, Jana PISTOVČÁKOVÁ, Alexandra ŠULCOVÁ, Ales STUCHLIK and Karel VALES. Pregnanolone glutamate, a novel use-dependent NMDA receptor inhibitor, exerts antidepressant-like properties in animal models. Frontiers in Behavioral Neuroscience. Lausanne: Frontiers, 2014, vol. 8, April, p. "130-1"-"130-10", 10 pp. ISSN 1662-5153. doi:10.3389/fnbeh.2014.00130.
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Basic information
Original name Pregnanolone glutamate, a novel use-dependent NMDA receptor inhibitor, exerts antidepressant-like properties in animal models
Authors HOLUBOVA, Kristina (203 Czech Republic), Tereza NEKOVAROVA (203 Czech Republic), Jana PISTOVČÁKOVÁ (203 Czech Republic, belonging to the institution), Alexandra ŠULCOVÁ (203 Czech Republic, guarantor, belonging to the institution), Ales STUCHLIK (203 Czech Republic) and Karel VALES (203 Czech Republic).
Edition Frontiers in Behavioral Neuroscience, Lausanne, Frontiers, 2014, 1662-5153.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30104 Pharmacology and pharmacy
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 3.270
RIV identification code RIV/00216224:14740/14:00075373
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.3389/fnbeh.2014.00130
UT WoS 000334289800001
Keywords in English pregnanolone glutamate; NMDAR; anxiolytic-like properties; antidepressant-like properties
Tags EL OK, kontrola MP, ok, podil, rivok
Tags International impact, Reviewed
Changed by Changed by: Martina Prášilová, učo 342282. Changed: 21. 10. 2014 11:39.
Abstract
A number of studies demonstrated a rapid onset of an antidepressant effect of non-competitive N-methyl-d-aspartic acid receptor (NMDAR) antagonists. Nonetheless, its therapeutic potential is rather limited, due to a high coincidence of negative side-effects. Therefore, the challenge seems to be in the development of NMDAR antagonists displaying antidepressant properties, and at the same time maintaining regular physiological function of the NMDAR. Previous results demonstrated that naturally occurring neurosteroid 3alfa5beta-pregnanolone sulfate shows pronounced inhibitory action by a use-dependent mechanism on the tonically active NMDAR. The aim of the present experiments is to find out whether the treatment with pregnanolone 3alfaC derivatives affects behavioral response to chronic and acute stress in an animal model of depression. Adult male mice were used throughout the study. Repeated social defeat and forced swimming tests were used as animal models of depression. The effect of the drugs on the locomotor/exploratory activity in the open-field test was also tested together with an effect on anxiety in the elevated plus maze. Results showed that pregnanolone glutamate (PG) did not induce hyperlocomotion, whereas both dizocilpine and ketamine significantly increased spontaneous locomotor activity in the open field. In the elevated plus maze, PG displayed anxiolytic-like properties. In forced swimming, PG prolonged time to the first floating. Acute treatment of PG disinhibited suppressed locomotor activity in the repeatedly defeated group-housed mice. Aggressive behavior of isolated mice was reduced after the chronic 30-day administration of PG. PG showed antidepressant-like and anxiolytic-like properties in the used tests, with minimal side-effects. Since PG combines GABAA receptor potentiation and use-dependent NMDAR inhibition, synthetic derivatives of neuroactive steroids present a promising strategy for the treatment of mood disorders.
Links
ED1.1.00/02.0068, research and development projectName: CEITEC - central european institute of technology
LM2011017, research and development projectName: Advanced Cell Immunotherapy Unit - ACIU
Investor: Ministry of Education, Youth and Sports of the CR
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