HOLUBOVA, Kristina, Tereza NEKOVAROVA, Jana PISTOVČÁKOVÁ, Alexandra ŠULCOVÁ, Ales STUCHLIK a 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, roč. 8, April, s. "130-1"-"130-10", 10 s. ISSN 1662-5153. doi:10.3389/fnbeh.2014.00130.
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Základní údaje
Originální název Pregnanolone glutamate, a novel use-dependent NMDA receptor inhibitor, exerts antidepressant-like properties in animal models
Autoři HOLUBOVA, Kristina (203 Česká republika), Tereza NEKOVAROVA (203 Česká republika), Jana PISTOVČÁKOVÁ (203 Česká republika, domácí), Alexandra ŠULCOVÁ (203 Česká republika, garant, domácí), Ales STUCHLIK (203 Česká republika) a Karel VALES (203 Česká republika).
Vydání Frontiers in Behavioral Neuroscience, Lausanne, Frontiers, 2014, 1662-5153.
Další údaje
Originální jazyk angličtina
Typ výsledku Článek v odborném periodiku
Obor 30104 Pharmacology and pharmacy
Stát vydavatele Švýcarsko
Utajení není předmětem státního či obchodního tajemství
WWW URL
Impakt faktor Impact factor: 3.270
Kód RIV RIV/00216224:14740/14:00075373
Organizační jednotka Středoevropský technologický institut
Doi http://dx.doi.org/10.3389/fnbeh.2014.00130
UT WoS 000334289800001
Klíčová slova anglicky pregnanolone glutamate; NMDAR; anxiolytic-like properties; antidepressant-like properties
Štítky EL OK, kontrola MP, ok, podil, rivok
Příznaky Mezinárodní význam, Recenzováno
Změnil Změnila: Martina Prášilová, učo 342282. Změněno: 21. 10. 2014 11:39.
Anotace
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.
Návaznosti
ED1.1.00/02.0068, projekt VaVNázev: CEITEC - central european institute of technology
LM2011017, projekt VaVNázev: Advanced Cell Immunotherapy Unit - ACIU
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Advanced cell immunotherapy unit BVI-ACIU
VytisknoutZobrazeno: 26. 6. 2022 00:26