Dependence of anxiolytic effects of the dipeptide TSPO ligand GD-23 on neurosteroid biosynthesis.
The elevated plus maze test showed that GD-23 (N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide), an original dipeptide ligand of TSPO, exerted anxiolytic effect when injected intraperitoneally at a dose of 0.5 mg/kg. This effect was completely blocked by the selective neurosteroid synthesis inhibitors, enzymes trilostane and finasteride. The same inhibitors do not prevent the anxiolytic effects of the benzodiazepine tranquillizer diazepam. The results of the study indicate the selective neurosteroidogenic mechanism of the anxiolytic action of GD-23.
Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences, ul. Baltiiskaya 8, Moscow, 125315, Russia. tata-sosnovka@mail.ru.
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Gudasheva
Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences, ul. Baltiiskaya 8, Moscow, 125315, Russia.
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Deeva
Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences, ul. Baltiiskaya 8, Moscow, 125315, Russia.
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Yarkova
Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences, ul. Baltiiskaya 8, Moscow, 125315, Russia.
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Seredenin
D000818:Animals; D021461:Animals, Outbred Strains; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D018120:Finasteride / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018377:Neurotransmitter Agents / Q000096:biosynthesis*; D011963:Receptors, GABA-A / Q000378:metabolism
D014151:Anti-Anxiety Agents; D002352:Carrier Proteins; D004151:Dipeptides; D004791:Enzyme Inhibitors; C000609774:N-carbobenzoxy-tryptophyl-isoleucine amide; D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; D013196:Dihydrotestosterone; C069997:Tspo protein, rat; D018120:Finasteride; C009954:trilostane; D003975:Diazepam