engleski

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

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.

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

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