Naslov
Mitochondrial Diazepam-Binding Inhibitor Receptor Complex Agonists Antagonize Dizocilpine Amnesia: Putative Role for Allopregnanolone

Autori
Romeo, Elena ; Živković, Ilija ; Costa Erminio

Izvornik
The Journal of pharmacology and experimental therapeutics (0022-3565) 270 (1994), 1; 89-96

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Mitocondrial diazepam-binding inhibitor ; Dizocilpine Amenzia ; Allopregnanolone ; THDOC

Sažetak
In rats trained to retain a passive avoidance response or to retrieve a learned task in the radial and water maze tests, a pretreatment with 2-hexyl-3- indoleacetamide (FGIN-1-27) (IC50 57 mu mol/kg p.o.) or 4'chlorodiazepam (4'CD) (15 mu mol/kg i.p.), two steroidogenic ligands at the mitochondria diazepam- binding inhibitor receptor complex (MDRC), antagonized the performance deficit elicited by dizocilpine (0.3 mu mol/kg i.p.), a noncompetitive N- methyl-D-aspariate (NMDA) receptor antagonist. The 1- (2- chlorophenyl)-N-methyl-N-(-1-methyl-propyl)-3- isoquinoline carboxamide (PK-11195), an antagonist at MDRC in vivo, failed to modify the disruptive effect of dizocilpine in the passive avoidance response but reversed the FGIN-1-27- or 4'CD- induced antagonism of dizocilpine behavioral actions. Pretreatment with pregnenolone sulfate (48 mu mol/kg i.p.), 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one (THDOC) (15 mu mol/kg i.v.) and 3 alpha-hydroxy-5 alpha-pregnan-20- one (allopregnanolone) (15 mu mol/kg i.v.) also reduced the passive avoidance retention deficit elicited by dizocilpine. The (17-beta)-17-[[bis(1- methylethyl)amino[carbonyl]androstane-3, 5-diene- 3- carboxylic acid (SKF-105111), a 5 alpha- reductase inhibitor, blocked the antagonism of dizocilpine behavioral actions by pregnenolone sulfate or by FGIN-1-27 but not those caused by THDOC or allopregnanolone either in normal or adrenalectomized-castrated rats. Thus, it is inferred that the amnesic effect of dizocilpine is counteracted by FGIN-1-27, 4'CD and pregnenolone sulfate because of their ability to increase brain accumulation of allopregnanolone.

Izvorni jezik
Engleski

Znanstvena područja
Psihologija

Napomena
Ovaj rad se bavi pitanjem amnezije i pokušajem da
se kemijskim tvarima utječe na kompleksne
receptore MDRC koji se lako vežu na poznati
diazepam. Receptorski antagonist NMDA (N-methyl-D-
aspartat) povećao je učinak amnezije skupa sa
dizolcipinom. Primjenom tvari FGIN-1-27 u znatnoj
mjeri je otklonjen deficit memorije kod životinja,
no još uvijek nedovoljno da bi bio obećavajući u
učinkovitom tretmanu amnezije

POVEZANOST RADA